MDedge Endocrinology

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

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

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.

The current trend of smaller medical practices consolidating into larger and larger ones has again called attention to the dicey issue of dismissing patients from a practice.

One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.

While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.

What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.

In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.

If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.

If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.

The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.

You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.

When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.

Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.

Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

The current trend of smaller medical practices consolidating into larger and larger ones has again called attention to the dicey issue of dismissing patients from a practice.

One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.

While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.

What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.

In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.

If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.

If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.

The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.

You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.

When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.

Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.

Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

The current trend of smaller medical practices consolidating into larger and larger ones has again called attention to the dicey issue of dismissing patients from a practice.

One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.

While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.

What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.

In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.

If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.

If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.

The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.

You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.

When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.

Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.

Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Overall risk for venous thromboembolism (VTE) in nonhospitalized COVID-19 patients is low, but some of those patients may have factors that increase the risk and warrant more surveillance, according to a new retrospective cohort study.

Though VTE risk is well studied and significant in those hospitalized with COVID, little is known about the risk in the outpatient setting, said the authors of the new research published online in JAMA Network Open.

The study was conducted at two integrated health care delivery systems in northern and southern California. Data were gathered from the Kaiser Permanente Virtual Data Warehouse and electronic health records.
 

Nearly 400,000 patients studied

Researchers, led by Margaret Fang, MD, with the division of hospital medicine, University of California, San Francisco, identified 398,530 outpatients with COVID-19 from Jan. 1, 2020, through Jan. 31, 2021.

VTE risk was low overall for ambulatory COVID patients.

“It is a reassuring study,” Dr. Fang said in an interview.

The researchers found that the risk is highest in the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% confidence interval, 0.51-0.67 per 100 person-years vs. 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days).
 

Factors linked with high VTE risk

They also found that several factors were linked with a higher risk of blood clots in the study population, including being at least 55 years old; being male; having a history of blood clots or thrombophilia; and a body mass index (BMI) of at least 30 kg/m².

The authors write, “These findings may help identify subsets of patients with COVID-19 who could benefit from VTE preventive strategies and more intensive short-term surveillance.”
 

Are routine anticoagulants justified?

Previously, randomized clinical trials have found that hospitalized patients with moderate COVID-19 may benefit from therapeutically dosed heparin anticoagulants but that therapeutic anticoagulation had no net benefit – and perhaps could even harm – patients who were critically ill with COVID.

“[M]uch less is known about the optimal thromboprophylaxis strategy for people with milder presentations of COVID-19 who do not require hospitalization,” they write.
 

Mild COVID VTE risk similar to general population

The authors note that rates of blood clots linked with COVID-19 are not much higher than the average blood clot rate in the general population, which is about 0.1-0.2 per 100 person-years.

Therefore, the results don’t justify routine administration of anticoagulation given the costs, inconvenience, and bleeding risks, they acknowledge.

Dr. Fang told this publication that it’s hard to know what to tell patients, given the overall low VTE risk. She said their study wasn’t designed to advise when to give prophylaxis.
 

Physicians should inform patients of their higher risk

“We should tell our patients who fall into these risk categories that blood clot is a concern after the development of COVID, especially in those first 30 days. And some people might benefit from increased surveillance,” Dr. Fang said.

”I think this study would support ongoing studies that look at whether selected patients benefit from VTE prophylaxis, for example low-dose anticoagulants,” she said.

Dr. Fang said the subgroup factors they found increased risk of blood clots for all patients, not just COVID-19 patients. It’s not clear why factors such as being male may increase blood clot risk, though that is consistent with previous literature, but higher risk with higher BMI might be related to a combination of inflammation or decreased mobility, she said.
 

Unanswered questions

Robert H. Hopkins Jr., MD, says the study helps answer a couple of important questions – that the VTE risk in nonhospitalized COVID-19 patients is low and when and for which patients risk may be highest.

However, there are several unanswered questions that argue against routine initiation of anticoagulants, notes the professor of internal medicine and pediatrics chief, division of general internal medicine, at University of Arkansas for Medical Sciences, Little Rock.

One is the change in the COVID variant landscape.

“We do not know whether rates of VTE are same or lower or higher with current circulating variants,” Dr. Hopkins said.

The authors acknowledge this as a limitation. Study data predate Omicron and subvariants, which appear to lower clinical severity, so it’s unclear whether VTE risk is different in this Omicron era.

Dr. Hopkins added another unknown: “We do not know whether vaccination affects rates of VTE in ambulatory breakthrough infection.”

Dr. Hopkins and the authors also note the lack of a control group in the study, to better compare risk.

Coauthor Dr. Prasad reports consultant fees from EpiExcellence LLC outside the submitted work. Coauthor Dr. Go reports grants paid to the division of research, Kaiser Permanente Northern California, from CSL Behring, Novartis, Bristol Meyers Squibb/Pfizer Alliance, and Janssen outside the submitted work.

The research was funded through Patient-Centered Outcomes Research Institute.

Dr. Hopkins reports no relevant financial relationships.

Overall risk for venous thromboembolism (VTE) in nonhospitalized COVID-19 patients is low, but some of those patients may have factors that increase the risk and warrant more surveillance, according to a new retrospective cohort study.

Though VTE risk is well studied and significant in those hospitalized with COVID, little is known about the risk in the outpatient setting, said the authors of the new research published online in JAMA Network Open.

The study was conducted at two integrated health care delivery systems in northern and southern California. Data were gathered from the Kaiser Permanente Virtual Data Warehouse and electronic health records.
 

Nearly 400,000 patients studied

Researchers, led by Margaret Fang, MD, with the division of hospital medicine, University of California, San Francisco, identified 398,530 outpatients with COVID-19 from Jan. 1, 2020, through Jan. 31, 2021.

VTE risk was low overall for ambulatory COVID patients.

“It is a reassuring study,” Dr. Fang said in an interview.

The researchers found that the risk is highest in the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% confidence interval, 0.51-0.67 per 100 person-years vs. 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days).
 

Factors linked with high VTE risk

They also found that several factors were linked with a higher risk of blood clots in the study population, including being at least 55 years old; being male; having a history of blood clots or thrombophilia; and a body mass index (BMI) of at least 30 kg/m².

The authors write, “These findings may help identify subsets of patients with COVID-19 who could benefit from VTE preventive strategies and more intensive short-term surveillance.”
 

Are routine anticoagulants justified?

Previously, randomized clinical trials have found that hospitalized patients with moderate COVID-19 may benefit from therapeutically dosed heparin anticoagulants but that therapeutic anticoagulation had no net benefit – and perhaps could even harm – patients who were critically ill with COVID.

“[M]uch less is known about the optimal thromboprophylaxis strategy for people with milder presentations of COVID-19 who do not require hospitalization,” they write.
 

Mild COVID VTE risk similar to general population

The authors note that rates of blood clots linked with COVID-19 are not much higher than the average blood clot rate in the general population, which is about 0.1-0.2 per 100 person-years.

Therefore, the results don’t justify routine administration of anticoagulation given the costs, inconvenience, and bleeding risks, they acknowledge.

Dr. Fang told this publication that it’s hard to know what to tell patients, given the overall low VTE risk. She said their study wasn’t designed to advise when to give prophylaxis.
 

Physicians should inform patients of their higher risk

“We should tell our patients who fall into these risk categories that blood clot is a concern after the development of COVID, especially in those first 30 days. And some people might benefit from increased surveillance,” Dr. Fang said.

”I think this study would support ongoing studies that look at whether selected patients benefit from VTE prophylaxis, for example low-dose anticoagulants,” she said.

Dr. Fang said the subgroup factors they found increased risk of blood clots for all patients, not just COVID-19 patients. It’s not clear why factors such as being male may increase blood clot risk, though that is consistent with previous literature, but higher risk with higher BMI might be related to a combination of inflammation or decreased mobility, she said.
 

Unanswered questions

Robert H. Hopkins Jr., MD, says the study helps answer a couple of important questions – that the VTE risk in nonhospitalized COVID-19 patients is low and when and for which patients risk may be highest.

However, there are several unanswered questions that argue against routine initiation of anticoagulants, notes the professor of internal medicine and pediatrics chief, division of general internal medicine, at University of Arkansas for Medical Sciences, Little Rock.

One is the change in the COVID variant landscape.

“We do not know whether rates of VTE are same or lower or higher with current circulating variants,” Dr. Hopkins said.

The authors acknowledge this as a limitation. Study data predate Omicron and subvariants, which appear to lower clinical severity, so it’s unclear whether VTE risk is different in this Omicron era.

Dr. Hopkins added another unknown: “We do not know whether vaccination affects rates of VTE in ambulatory breakthrough infection.”

Dr. Hopkins and the authors also note the lack of a control group in the study, to better compare risk.

Coauthor Dr. Prasad reports consultant fees from EpiExcellence LLC outside the submitted work. Coauthor Dr. Go reports grants paid to the division of research, Kaiser Permanente Northern California, from CSL Behring, Novartis, Bristol Meyers Squibb/Pfizer Alliance, and Janssen outside the submitted work.

The research was funded through Patient-Centered Outcomes Research Institute.

Dr. Hopkins reports no relevant financial relationships.

Overall risk for venous thromboembolism (VTE) in nonhospitalized COVID-19 patients is low, but some of those patients may have factors that increase the risk and warrant more surveillance, according to a new retrospective cohort study.

Though VTE risk is well studied and significant in those hospitalized with COVID, little is known about the risk in the outpatient setting, said the authors of the new research published online in JAMA Network Open.

The study was conducted at two integrated health care delivery systems in northern and southern California. Data were gathered from the Kaiser Permanente Virtual Data Warehouse and electronic health records.
 

Nearly 400,000 patients studied

Researchers, led by Margaret Fang, MD, with the division of hospital medicine, University of California, San Francisco, identified 398,530 outpatients with COVID-19 from Jan. 1, 2020, through Jan. 31, 2021.

VTE risk was low overall for ambulatory COVID patients.

“It is a reassuring study,” Dr. Fang said in an interview.

The researchers found that the risk is highest in the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% confidence interval, 0.51-0.67 per 100 person-years vs. 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days).
 

Factors linked with high VTE risk

They also found that several factors were linked with a higher risk of blood clots in the study population, including being at least 55 years old; being male; having a history of blood clots or thrombophilia; and a body mass index (BMI) of at least 30 kg/m².

The authors write, “These findings may help identify subsets of patients with COVID-19 who could benefit from VTE preventive strategies and more intensive short-term surveillance.”
 

Are routine anticoagulants justified?

Previously, randomized clinical trials have found that hospitalized patients with moderate COVID-19 may benefit from therapeutically dosed heparin anticoagulants but that therapeutic anticoagulation had no net benefit – and perhaps could even harm – patients who were critically ill with COVID.

“[M]uch less is known about the optimal thromboprophylaxis strategy for people with milder presentations of COVID-19 who do not require hospitalization,” they write.
 

Mild COVID VTE risk similar to general population

The authors note that rates of blood clots linked with COVID-19 are not much higher than the average blood clot rate in the general population, which is about 0.1-0.2 per 100 person-years.

Therefore, the results don’t justify routine administration of anticoagulation given the costs, inconvenience, and bleeding risks, they acknowledge.

Dr. Fang told this publication that it’s hard to know what to tell patients, given the overall low VTE risk. She said their study wasn’t designed to advise when to give prophylaxis.
 

Physicians should inform patients of their higher risk

“We should tell our patients who fall into these risk categories that blood clot is a concern after the development of COVID, especially in those first 30 days. And some people might benefit from increased surveillance,” Dr. Fang said.

”I think this study would support ongoing studies that look at whether selected patients benefit from VTE prophylaxis, for example low-dose anticoagulants,” she said.

Dr. Fang said the subgroup factors they found increased risk of blood clots for all patients, not just COVID-19 patients. It’s not clear why factors such as being male may increase blood clot risk, though that is consistent with previous literature, but higher risk with higher BMI might be related to a combination of inflammation or decreased mobility, she said.
 

Unanswered questions

Robert H. Hopkins Jr., MD, says the study helps answer a couple of important questions – that the VTE risk in nonhospitalized COVID-19 patients is low and when and for which patients risk may be highest.

However, there are several unanswered questions that argue against routine initiation of anticoagulants, notes the professor of internal medicine and pediatrics chief, division of general internal medicine, at University of Arkansas for Medical Sciences, Little Rock.

One is the change in the COVID variant landscape.

“We do not know whether rates of VTE are same or lower or higher with current circulating variants,” Dr. Hopkins said.

The authors acknowledge this as a limitation. Study data predate Omicron and subvariants, which appear to lower clinical severity, so it’s unclear whether VTE risk is different in this Omicron era.

Dr. Hopkins added another unknown: “We do not know whether vaccination affects rates of VTE in ambulatory breakthrough infection.”

Dr. Hopkins and the authors also note the lack of a control group in the study, to better compare risk.

Coauthor Dr. Prasad reports consultant fees from EpiExcellence LLC outside the submitted work. Coauthor Dr. Go reports grants paid to the division of research, Kaiser Permanente Northern California, from CSL Behring, Novartis, Bristol Meyers Squibb/Pfizer Alliance, and Janssen outside the submitted work.

The research was funded through Patient-Centered Outcomes Research Institute.

Dr. Hopkins reports no relevant financial relationships.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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

Lung development in the fetus may be adversely affected by a mother’s gestational diabetes, based on data from in vivo, in vitro, and ex vivo studies.

Gestational diabetes mellitus (GDM) has recently been associated with fetal lung underdevelopment (FLUD) and delayed lung maturation that may lead to immediate respiratory distress in newborns and later chronic lung disease, Pengzheng Chen, PhD, of Shandong University, Jinan, China, and colleagues wrote.

Antenatal corticosteroids are considered an effective treatment for gestational fetal lung underdevelopment, but recent studies have shown adverse effects of these medications, and therefore more research is needed to identify the etiology and pathogenesis of FLUD induced by GDM, they said.

In a study published in the International Journal of Nanomedicine, the researchers collected umbilical cord blood samples from patients with GDM and matched controls at a single hospital in China.

“Using an ex vivo exosome exposure model of fetal lung explants, we observed the morphological alteration of lung explants and evaluated the expression of molecules involved in lung development,” the researchers wrote.

Fetal lung underdevelopment was more common after exposure to exosomes from the umbilical cord plasma of individuals with gestational diabetes mellitus, compared with exosomes from healthy controls.

The researchers also used mouse models to examine the effects of exosomes on fetal lung development in vivo. They found that exosomes associated with GDM impeded the growth, branching morphogenesis, and maturation of fetal lungs in mouse models. In addition, the expression of the apoptotic biomarkers known as BAX, BIM, and cleaved CASPASE-3 was up-regulated in GDMUB-exosomes and HG-exos groups, but the antiapoptotic protein BCL-2 was down-regulated; this further supported the negative impact of GDM exomes on fetal lung development, the researchers said.

The researchers then conducted miRNA sequencing, which showed that the miRNA in placenta-derived exosomes from GDM pregnancies were distinct from the miRNA in exosomes from healthy control pregnancies.

The study findings were limited by several factors including the impurity of the isolated placenta-derived exosomes from the umbilical cord blood plasma, which were not placenta specific, the researchers noted. Other limitations included the lack of data on different stages of lung development, and more research is needed to validate miRNAs and to explore the signally pathways involved in fetal lung development.

However, the study is the first known to demonstrate an adverse effect of GDM on fetal lung development via in vitro, ex vivo, and in vitro models, they said.

“These data highlight an emerging role of placenta-derived exosomes in the pathogenesis of fetal lung underdevelopment in GDM pregnancies, and provide a novel strategy for maternal-fetal communication,” they concluded.

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

Lung development in the fetus may be adversely affected by a mother’s gestational diabetes, based on data from in vivo, in vitro, and ex vivo studies.

Gestational diabetes mellitus (GDM) has recently been associated with fetal lung underdevelopment (FLUD) and delayed lung maturation that may lead to immediate respiratory distress in newborns and later chronic lung disease, Pengzheng Chen, PhD, of Shandong University, Jinan, China, and colleagues wrote.

Antenatal corticosteroids are considered an effective treatment for gestational fetal lung underdevelopment, but recent studies have shown adverse effects of these medications, and therefore more research is needed to identify the etiology and pathogenesis of FLUD induced by GDM, they said.

In a study published in the International Journal of Nanomedicine, the researchers collected umbilical cord blood samples from patients with GDM and matched controls at a single hospital in China.

“Using an ex vivo exosome exposure model of fetal lung explants, we observed the morphological alteration of lung explants and evaluated the expression of molecules involved in lung development,” the researchers wrote.

Fetal lung underdevelopment was more common after exposure to exosomes from the umbilical cord plasma of individuals with gestational diabetes mellitus, compared with exosomes from healthy controls.

The researchers also used mouse models to examine the effects of exosomes on fetal lung development in vivo. They found that exosomes associated with GDM impeded the growth, branching morphogenesis, and maturation of fetal lungs in mouse models. In addition, the expression of the apoptotic biomarkers known as BAX, BIM, and cleaved CASPASE-3 was up-regulated in GDMUB-exosomes and HG-exos groups, but the antiapoptotic protein BCL-2 was down-regulated; this further supported the negative impact of GDM exomes on fetal lung development, the researchers said.

The researchers then conducted miRNA sequencing, which showed that the miRNA in placenta-derived exosomes from GDM pregnancies were distinct from the miRNA in exosomes from healthy control pregnancies.

The study findings were limited by several factors including the impurity of the isolated placenta-derived exosomes from the umbilical cord blood plasma, which were not placenta specific, the researchers noted. Other limitations included the lack of data on different stages of lung development, and more research is needed to validate miRNAs and to explore the signally pathways involved in fetal lung development.

However, the study is the first known to demonstrate an adverse effect of GDM on fetal lung development via in vitro, ex vivo, and in vitro models, they said.

“These data highlight an emerging role of placenta-derived exosomes in the pathogenesis of fetal lung underdevelopment in GDM pregnancies, and provide a novel strategy for maternal-fetal communication,” they concluded.

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

Lung development in the fetus may be adversely affected by a mother’s gestational diabetes, based on data from in vivo, in vitro, and ex vivo studies.

Gestational diabetes mellitus (GDM) has recently been associated with fetal lung underdevelopment (FLUD) and delayed lung maturation that may lead to immediate respiratory distress in newborns and later chronic lung disease, Pengzheng Chen, PhD, of Shandong University, Jinan, China, and colleagues wrote.

Antenatal corticosteroids are considered an effective treatment for gestational fetal lung underdevelopment, but recent studies have shown adverse effects of these medications, and therefore more research is needed to identify the etiology and pathogenesis of FLUD induced by GDM, they said.

In a study published in the International Journal of Nanomedicine, the researchers collected umbilical cord blood samples from patients with GDM and matched controls at a single hospital in China.

“Using an ex vivo exosome exposure model of fetal lung explants, we observed the morphological alteration of lung explants and evaluated the expression of molecules involved in lung development,” the researchers wrote.

Fetal lung underdevelopment was more common after exposure to exosomes from the umbilical cord plasma of individuals with gestational diabetes mellitus, compared with exosomes from healthy controls.

The researchers also used mouse models to examine the effects of exosomes on fetal lung development in vivo. They found that exosomes associated with GDM impeded the growth, branching morphogenesis, and maturation of fetal lungs in mouse models. In addition, the expression of the apoptotic biomarkers known as BAX, BIM, and cleaved CASPASE-3 was up-regulated in GDMUB-exosomes and HG-exos groups, but the antiapoptotic protein BCL-2 was down-regulated; this further supported the negative impact of GDM exomes on fetal lung development, the researchers said.

The researchers then conducted miRNA sequencing, which showed that the miRNA in placenta-derived exosomes from GDM pregnancies were distinct from the miRNA in exosomes from healthy control pregnancies.

The study findings were limited by several factors including the impurity of the isolated placenta-derived exosomes from the umbilical cord blood plasma, which were not placenta specific, the researchers noted. Other limitations included the lack of data on different stages of lung development, and more research is needed to validate miRNAs and to explore the signally pathways involved in fetal lung development.

However, the study is the first known to demonstrate an adverse effect of GDM on fetal lung development via in vitro, ex vivo, and in vitro models, they said.

“These data highlight an emerging role of placenta-derived exosomes in the pathogenesis of fetal lung underdevelopment in GDM pregnancies, and provide a novel strategy for maternal-fetal communication,” they concluded.

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