I recall in college we used to talk a lot about the relationship between town and gown, that is, the town community and the academic community, and how they relate to each other. This remains pertinent today as we consider the dermatology academic community and practicing dermatologists. There should be a virtuous circle between dermatologists in their community and their academic medical center.

Academic medical centers are up to date and on the cutting edge of science and treatments – and happy to share with community dermatologists. This is where you will learn about teledermatology and how to use the latest biologics.

They provide educational opportunities such as grand rounds and visiting speakers. They allow community physicians to attend staff and resident lectures, bring their most challenging cases to grand rounds, and get feedback and suggestions, with everyone learning from the experience. They host dermatology events for all. They allow community physicians to staff resident clinics where both benefit from the interaction. The academic center provides a charity care network for the community – and usually provides the experts of last resort for difficult cases as they are often on the cutting edge of research and newest treatments.

Large multispecialty practices– and private equity groups – are not going to fill this role.

Dermatology is a highly isolated specialty and the interaction with others at the academic center may be the only physical link to the outside world of medicine. Having an academic dermatology program in your community is a serious asset that community dermatologists should appreciate and support.

However, as the gown supports the town, so should the town support the gown. There is a pervasive inaccuracy in the community that these academic dermatology departments are supported by government funds or a “state line” of support. This is incorrect. These departments support themselves with clinical work. In addition, the dean and/or the medical school takes a generous cut out of their profits, and the departments also must compete – furiously – for grants, of which the medical school immediately takes about 55% for indirect “overhead,” a frequent complaint of academic physicians.

If you practice near such an academic center and benefit from its virtuous circle, you can consider sending them some of your dermatopathology or Mohs, even if you are a large group and could handle them yourselves. You can join the local dermatologic society and bring cases to grand rounds. You can offer to teach the residents in their clinic, or in your office, and expose them to real life practice.

If you have the means, you could consider funding a lectureship or an endowed departmental chair. No matter the virtual content available online, the quality of learning one on one from another specialist cannot be beat. So make the effort to visit the gown from the town. You will be warmly welcomed and join a virtuous circle of lifelong learners.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

I recall in college we used to talk a lot about the relationship between town and gown, that is, the town community and the academic community, and how they relate to each other. This remains pertinent today as we consider the dermatology academic community and practicing dermatologists. There should be a virtuous circle between dermatologists in their community and their academic medical center.

Academic medical centers are up to date and on the cutting edge of science and treatments – and happy to share with community dermatologists. This is where you will learn about teledermatology and how to use the latest biologics.

They provide educational opportunities such as grand rounds and visiting speakers. They allow community physicians to attend staff and resident lectures, bring their most challenging cases to grand rounds, and get feedback and suggestions, with everyone learning from the experience. They host dermatology events for all. They allow community physicians to staff resident clinics where both benefit from the interaction. The academic center provides a charity care network for the community – and usually provides the experts of last resort for difficult cases as they are often on the cutting edge of research and newest treatments.

Large multispecialty practices– and private equity groups – are not going to fill this role.

Dermatology is a highly isolated specialty and the interaction with others at the academic center may be the only physical link to the outside world of medicine. Having an academic dermatology program in your community is a serious asset that community dermatologists should appreciate and support.

However, as the gown supports the town, so should the town support the gown. There is a pervasive inaccuracy in the community that these academic dermatology departments are supported by government funds or a “state line” of support. This is incorrect. These departments support themselves with clinical work. In addition, the dean and/or the medical school takes a generous cut out of their profits, and the departments also must compete – furiously – for grants, of which the medical school immediately takes about 55% for indirect “overhead,” a frequent complaint of academic physicians.

If you practice near such an academic center and benefit from its virtuous circle, you can consider sending them some of your dermatopathology or Mohs, even if you are a large group and could handle them yourselves. You can join the local dermatologic society and bring cases to grand rounds. You can offer to teach the residents in their clinic, or in your office, and expose them to real life practice.

If you have the means, you could consider funding a lectureship or an endowed departmental chair. No matter the virtual content available online, the quality of learning one on one from another specialist cannot be beat. So make the effort to visit the gown from the town. You will be warmly welcomed and join a virtuous circle of lifelong learners.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

I recall in college we used to talk a lot about the relationship between town and gown, that is, the town community and the academic community, and how they relate to each other. This remains pertinent today as we consider the dermatology academic community and practicing dermatologists. There should be a virtuous circle between dermatologists in their community and their academic medical center.

Academic medical centers are up to date and on the cutting edge of science and treatments – and happy to share with community dermatologists. This is where you will learn about teledermatology and how to use the latest biologics.

They provide educational opportunities such as grand rounds and visiting speakers. They allow community physicians to attend staff and resident lectures, bring their most challenging cases to grand rounds, and get feedback and suggestions, with everyone learning from the experience. They host dermatology events for all. They allow community physicians to staff resident clinics where both benefit from the interaction. The academic center provides a charity care network for the community – and usually provides the experts of last resort for difficult cases as they are often on the cutting edge of research and newest treatments.

Large multispecialty practices– and private equity groups – are not going to fill this role.

Dermatology is a highly isolated specialty and the interaction with others at the academic center may be the only physical link to the outside world of medicine. Having an academic dermatology program in your community is a serious asset that community dermatologists should appreciate and support.

However, as the gown supports the town, so should the town support the gown. There is a pervasive inaccuracy in the community that these academic dermatology departments are supported by government funds or a “state line” of support. This is incorrect. These departments support themselves with clinical work. In addition, the dean and/or the medical school takes a generous cut out of their profits, and the departments also must compete – furiously – for grants, of which the medical school immediately takes about 55% for indirect “overhead,” a frequent complaint of academic physicians.

If you practice near such an academic center and benefit from its virtuous circle, you can consider sending them some of your dermatopathology or Mohs, even if you are a large group and could handle them yourselves. You can join the local dermatologic society and bring cases to grand rounds. You can offer to teach the residents in their clinic, or in your office, and expose them to real life practice.

If you have the means, you could consider funding a lectureship or an endowed departmental chair. No matter the virtual content available online, the quality of learning one on one from another specialist cannot be beat. So make the effort to visit the gown from the town. You will be warmly welcomed and join a virtuous circle of lifelong learners.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

WASHINGTON – Of patients with ST-elevation MI (STEMI) complicated by cardiogenic shock, 13% are readmitted within 30 days and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.

Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
 

“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.

In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.

Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.

The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.

“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.

“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.

WASHINGTON – Of patients with ST-elevation MI (STEMI) complicated by cardiogenic shock, 13% are readmitted within 30 days and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.

Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
 

“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.

In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.

Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.

The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.

“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.

“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.

WASHINGTON – Of patients with ST-elevation MI (STEMI) complicated by cardiogenic shock, 13% are readmitted within 30 days and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.

Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
 

“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.

In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.

Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.

The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.

“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.

“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.

NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.

“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.

“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.

Asthma affects 10% of the world population, and it’s becoming increasingly understood that obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.

“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”

The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.

Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”

Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”

A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.

Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.

Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m², of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.

Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.

These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.

Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.

The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”

Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.

koakes@mdedge.com

SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.

NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.

“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.

“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.

Asthma affects 10% of the world population, and it’s becoming increasingly understood that obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.

“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”

The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.

Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”

Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”

A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.

Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.

Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m², of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.

Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.

These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.

Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.

The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”

Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.

koakes@mdedge.com

SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.

NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.

“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.

“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.

Asthma affects 10% of the world population, and it’s becoming increasingly understood that obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.

“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”

The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.

Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”

Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”

A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.

Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.

Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m², of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.

Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.

These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.

Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.

The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”

Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.

koakes@mdedge.com

SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.

PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Andrew D. Bowser/MDedge News

“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.

The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”

“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.

From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.

Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.

By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.

However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”

Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.

That was a “reasonable study” but more research needs to be done, Dr. Brant said.

“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”

Dr. Brant indicated that he had no relevant financial relationships to disclose.

Global Academy and this news organization are owned by the same parent company.

PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Andrew D. Bowser/MDedge News

“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.

The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”

“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.

From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.

Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.

By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.

However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”

Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.

That was a “reasonable study” but more research needs to be done, Dr. Brant said.

“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”

Dr. Brant indicated that he had no relevant financial relationships to disclose.

Global Academy and this news organization are owned by the same parent company.

PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Andrew D. Bowser/MDedge News

“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.

The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”

“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.

From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.

Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.

By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.

However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”

Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.

That was a “reasonable study” but more research needs to be done, Dr. Brant said.

“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”

Dr. Brant indicated that he had no relevant financial relationships to disclose.

Global Academy and this news organization are owned by the same parent company.

DENVER – Combining gold microparticles with energy from a standard dermatology laser represents a new in-office treatment option for patients with mild to moderate acne, according to Jill S. Waibel, MD.

“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”

The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.

Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”

Energy was delivered at a fluency of 25-34 J/cm² and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.

Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.

After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.

“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”

The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.

dbrunk@mdedge.com

DENVER – Combining gold microparticles with energy from a standard dermatology laser represents a new in-office treatment option for patients with mild to moderate acne, according to Jill S. Waibel, MD.

“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”

The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.

Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”

Energy was delivered at a fluency of 25-34 J/cm² and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.

Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.

After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.

“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”

The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.

dbrunk@mdedge.com

DENVER – Combining gold microparticles with energy from a standard dermatology laser represents a new in-office treatment option for patients with mild to moderate acne, according to Jill S. Waibel, MD.

“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”

The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.

Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”

Energy was delivered at a fluency of 25-34 J/cm² and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.

Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.

After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.

“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”

The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.

dbrunk@mdedge.com

Use of rituximab for B-cell depletion was not associated with clinical improvement of fatigue scores for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), according to results from the phase 3 RituxME trial.

Courtesy Kristin Risa

“The lack of clinical effect of B-cell depletion in this trial weakens the case for an important role of B lymphocytes in ME/CFS but does not exclude an immunologic basis,” Øystein Fluge, MD, PhD, of the department of oncology and medical physics at Haukeland University Hospital in Bergen, Norway, and his colleagues wrote April 1 in Annals of Internal Medicine.

The investigators noted that the basis for testing the effects of a B-cell–depleting intervention on clinical symptoms in patients with ME/CFS came from observations of its potential benefit in a subgroup of patients in previous studies. Dr. Fluge and his colleagues performed a three-patient case series in their own group that found benefit for patients who received rituximab for treatment of CFS (BMC Neurol. 2009 May 8;9:28. doi: 10.1186/1471-2377-9-28). A phase 2 trial of 30 patients with CFS also performed by his own group found improved fatigue scores in 66.7% of patients in the rituximab group, compared with placebo (PLOS One. 2011 Oct 19. doi: 10.1371/journal.pone.0026358).

In the double-blinded RituxME trial, 151 patients with ME/CFS from four university hospitals and one general hospital in Norway were recruited and randomized to receive infusions of rituximab (n = 77) or placebo (n = 74). The patients were aged 18-65 years old and had the disease ranging from 2 years to 15 years. Patients reported and rated their ME/CFS symptoms at baseline as well as completed forms for the SF-36, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, and modified DePaul Symptom Questionnaire out to 24 months. The rituximab group received two infusions at 500 mg/m² across body surface area at 2 weeks apart. They then received 500-mg maintenance infusions at 3 months, 6 months, 9 months, and 12 months where they also self-reported changes in ME/CFS symptoms.

There were no significant differences between groups regarding fatigue score at any follow-up period, with an average between-group difference of 0.02 at 24 months (95% confidence interval, –0.27 to 0.31). The overall response rate was 26% with rituximab and 35% with placebo. Dr. Fluge and his colleagues also noted no significant differences regarding SF-36 scores, function level, and fatigue severity between groups.

Adverse event rates were higher in the rituximab group (63 patients; 82%) than in the placebo group (48 patients; 65%), and these were more often attributed to treatment for those taking rituximab (26 patients [34%]) than for placebo (12 patients [16%]). Adverse events requiring hospitalization also occurred more often among those taking rituximab (31 events in 20 patients [26%]) than for those who took placebo (16 events in 14 patients [19%]).

Some of the weaknesses of the trial included its use of self-referral and self-reported symptom scores, which might have been subject to recall bias. In commenting on the difference in outcome between the phase 3 trial and others, Dr. Fluge and his associates said the discrepancy could potentially be high expectations in the placebo group, unknown factors surrounding symptom variation in ME/CFS patients, and unknown patient selection effects.

“[T]he negative outcome of RituxME should spur research to assess patient subgroups and further elucidate disease mechanisms, of which recently disclosed impairment of energy metabolism may be important,” Dr. Fluge and his coauthors wrote.

The trial was funded by grants to the researchers from the Norwegian Research Council, the Norwegian Regional Health Trusts, the MEandYou Foundation, the Norwegian ME Association, and the legacy of Torstein Hereid.

SOURCE: Fluge Ø et al. Ann Intern Med. 2019 Apr 1. doi: 10.7326/M18-1451

Use of rituximab for B-cell depletion was not associated with clinical improvement of fatigue scores for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), according to results from the phase 3 RituxME trial.

Courtesy Kristin Risa

“The lack of clinical effect of B-cell depletion in this trial weakens the case for an important role of B lymphocytes in ME/CFS but does not exclude an immunologic basis,” Øystein Fluge, MD, PhD, of the department of oncology and medical physics at Haukeland University Hospital in Bergen, Norway, and his colleagues wrote April 1 in Annals of Internal Medicine.

The investigators noted that the basis for testing the effects of a B-cell–depleting intervention on clinical symptoms in patients with ME/CFS came from observations of its potential benefit in a subgroup of patients in previous studies. Dr. Fluge and his colleagues performed a three-patient case series in their own group that found benefit for patients who received rituximab for treatment of CFS (BMC Neurol. 2009 May 8;9:28. doi: 10.1186/1471-2377-9-28). A phase 2 trial of 30 patients with CFS also performed by his own group found improved fatigue scores in 66.7% of patients in the rituximab group, compared with placebo (PLOS One. 2011 Oct 19. doi: 10.1371/journal.pone.0026358).

In the double-blinded RituxME trial, 151 patients with ME/CFS from four university hospitals and one general hospital in Norway were recruited and randomized to receive infusions of rituximab (n = 77) or placebo (n = 74). The patients were aged 18-65 years old and had the disease ranging from 2 years to 15 years. Patients reported and rated their ME/CFS symptoms at baseline as well as completed forms for the SF-36, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, and modified DePaul Symptom Questionnaire out to 24 months. The rituximab group received two infusions at 500 mg/m² across body surface area at 2 weeks apart. They then received 500-mg maintenance infusions at 3 months, 6 months, 9 months, and 12 months where they also self-reported changes in ME/CFS symptoms.

There were no significant differences between groups regarding fatigue score at any follow-up period, with an average between-group difference of 0.02 at 24 months (95% confidence interval, –0.27 to 0.31). The overall response rate was 26% with rituximab and 35% with placebo. Dr. Fluge and his colleagues also noted no significant differences regarding SF-36 scores, function level, and fatigue severity between groups.

Adverse event rates were higher in the rituximab group (63 patients; 82%) than in the placebo group (48 patients; 65%), and these were more often attributed to treatment for those taking rituximab (26 patients [34%]) than for placebo (12 patients [16%]). Adverse events requiring hospitalization also occurred more often among those taking rituximab (31 events in 20 patients [26%]) than for those who took placebo (16 events in 14 patients [19%]).

Some of the weaknesses of the trial included its use of self-referral and self-reported symptom scores, which might have been subject to recall bias. In commenting on the difference in outcome between the phase 3 trial and others, Dr. Fluge and his associates said the discrepancy could potentially be high expectations in the placebo group, unknown factors surrounding symptom variation in ME/CFS patients, and unknown patient selection effects.

“[T]he negative outcome of RituxME should spur research to assess patient subgroups and further elucidate disease mechanisms, of which recently disclosed impairment of energy metabolism may be important,” Dr. Fluge and his coauthors wrote.

The trial was funded by grants to the researchers from the Norwegian Research Council, the Norwegian Regional Health Trusts, the MEandYou Foundation, the Norwegian ME Association, and the legacy of Torstein Hereid.

SOURCE: Fluge Ø et al. Ann Intern Med. 2019 Apr 1. doi: 10.7326/M18-1451

Use of rituximab for B-cell depletion was not associated with clinical improvement of fatigue scores for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), according to results from the phase 3 RituxME trial.

Courtesy Kristin Risa

“The lack of clinical effect of B-cell depletion in this trial weakens the case for an important role of B lymphocytes in ME/CFS but does not exclude an immunologic basis,” Øystein Fluge, MD, PhD, of the department of oncology and medical physics at Haukeland University Hospital in Bergen, Norway, and his colleagues wrote April 1 in Annals of Internal Medicine.

The investigators noted that the basis for testing the effects of a B-cell–depleting intervention on clinical symptoms in patients with ME/CFS came from observations of its potential benefit in a subgroup of patients in previous studies. Dr. Fluge and his colleagues performed a three-patient case series in their own group that found benefit for patients who received rituximab for treatment of CFS (BMC Neurol. 2009 May 8;9:28. doi: 10.1186/1471-2377-9-28). A phase 2 trial of 30 patients with CFS also performed by his own group found improved fatigue scores in 66.7% of patients in the rituximab group, compared with placebo (PLOS One. 2011 Oct 19. doi: 10.1371/journal.pone.0026358).

In the double-blinded RituxME trial, 151 patients with ME/CFS from four university hospitals and one general hospital in Norway were recruited and randomized to receive infusions of rituximab (n = 77) or placebo (n = 74). The patients were aged 18-65 years old and had the disease ranging from 2 years to 15 years. Patients reported and rated their ME/CFS symptoms at baseline as well as completed forms for the SF-36, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, and modified DePaul Symptom Questionnaire out to 24 months. The rituximab group received two infusions at 500 mg/m² across body surface area at 2 weeks apart. They then received 500-mg maintenance infusions at 3 months, 6 months, 9 months, and 12 months where they also self-reported changes in ME/CFS symptoms.

There were no significant differences between groups regarding fatigue score at any follow-up period, with an average between-group difference of 0.02 at 24 months (95% confidence interval, –0.27 to 0.31). The overall response rate was 26% with rituximab and 35% with placebo. Dr. Fluge and his colleagues also noted no significant differences regarding SF-36 scores, function level, and fatigue severity between groups.

Adverse event rates were higher in the rituximab group (63 patients; 82%) than in the placebo group (48 patients; 65%), and these were more often attributed to treatment for those taking rituximab (26 patients [34%]) than for placebo (12 patients [16%]). Adverse events requiring hospitalization also occurred more often among those taking rituximab (31 events in 20 patients [26%]) than for those who took placebo (16 events in 14 patients [19%]).

Some of the weaknesses of the trial included its use of self-referral and self-reported symptom scores, which might have been subject to recall bias. In commenting on the difference in outcome between the phase 3 trial and others, Dr. Fluge and his associates said the discrepancy could potentially be high expectations in the placebo group, unknown factors surrounding symptom variation in ME/CFS patients, and unknown patient selection effects.

“[T]he negative outcome of RituxME should spur research to assess patient subgroups and further elucidate disease mechanisms, of which recently disclosed impairment of energy metabolism may be important,” Dr. Fluge and his coauthors wrote.

The trial was funded by grants to the researchers from the Norwegian Research Council, the Norwegian Regional Health Trusts, the MEandYou Foundation, the Norwegian ME Association, and the legacy of Torstein Hereid.

SOURCE: Fluge Ø et al. Ann Intern Med. 2019 Apr 1. doi: 10.7326/M18-1451

PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.

With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.

“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”

Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.

Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.

Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.

“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.

PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.

With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.

“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”

Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.

Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.

Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.

“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.

PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.

With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.

“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”

Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.

Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.

Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.

“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.

DALLAS – Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Jake Remaly/MDedge News

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Petracca M et al. ACTRIMS Forum 2019, Abstract 160.

DALLAS – Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Jake Remaly/MDedge News

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Petracca M et al. ACTRIMS Forum 2019, Abstract 160.

DALLAS – Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Jake Remaly/MDedge News

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Petracca M et al. ACTRIMS Forum 2019, Abstract 160.

As artificial intelligence (AI) takes on more and more tasks in medical care that mimic human cognition, hospitalists and other physicians will need to adapt to a changing role.

Today AI can identify tuberculosis infections in chest radiographs with almost complete accuracy, diagnose melanoma from images of skin lesions more accurately than dermatologists can, and identify metastatic cells in images of lymph node tissue more accurately than pathologists can. The next 20 years are likely to see further acceleration in the capabilities, according to a recent article by S. Claiborne Johnston, MD, PhD.

“AI will change the practice of medicine. The art of medicine, including all the humanistic components, will only become more important over time. As dean of a medical school, I’m training students who will be practicing in 2065,” Dr. Johnston said. “If I’m not thinking about the future, I’m failing my students and the society they will serve.”

The contributions of AI will shift the emphasis for human caregivers to the caring. Studies have shown that the skills of caring are associated with improved patient outcomes, but most medical schools allocate substantial time in the curriculum to memorization and analysis – tasks that will become less demanding as artificial intelligence improves. The art of caring – communication, empathy, shared decision making, leadership, and team building – is usually a minor part of the medical school curriculum.

Effective leadership and creativity are distant aspirations for artificial intelligence but are growing needs in a system of care that is ever more complex.

At Dr. Johnston’s school, the Dell Medical School at the University of Texas at Austin, they have reduced the duration of basic science instruction to 12 months and emphasized group problem solving, while deemphasizing memorization. This has freed up additional time for instruction in the art of caring, leadership, and creativity.

“Hospitalists should acknowledge the value of caring,” Dr. Johnston said. “They do it every day with every patient. It is important today, and will be more important tomorrow.”
 

Reference

Johnston SC. Anticipating and training the physician of the future: The importance of caring in an age of artificial intelligence. Acad Med. 2018;93(8):1105-6. doi: 10.1097/ACM.0000000000002175.

As artificial intelligence (AI) takes on more and more tasks in medical care that mimic human cognition, hospitalists and other physicians will need to adapt to a changing role.

Today AI can identify tuberculosis infections in chest radiographs with almost complete accuracy, diagnose melanoma from images of skin lesions more accurately than dermatologists can, and identify metastatic cells in images of lymph node tissue more accurately than pathologists can. The next 20 years are likely to see further acceleration in the capabilities, according to a recent article by S. Claiborne Johnston, MD, PhD.

“AI will change the practice of medicine. The art of medicine, including all the humanistic components, will only become more important over time. As dean of a medical school, I’m training students who will be practicing in 2065,” Dr. Johnston said. “If I’m not thinking about the future, I’m failing my students and the society they will serve.”

The contributions of AI will shift the emphasis for human caregivers to the caring. Studies have shown that the skills of caring are associated with improved patient outcomes, but most medical schools allocate substantial time in the curriculum to memorization and analysis – tasks that will become less demanding as artificial intelligence improves. The art of caring – communication, empathy, shared decision making, leadership, and team building – is usually a minor part of the medical school curriculum.

Effective leadership and creativity are distant aspirations for artificial intelligence but are growing needs in a system of care that is ever more complex.

At Dr. Johnston’s school, the Dell Medical School at the University of Texas at Austin, they have reduced the duration of basic science instruction to 12 months and emphasized group problem solving, while deemphasizing memorization. This has freed up additional time for instruction in the art of caring, leadership, and creativity.

“Hospitalists should acknowledge the value of caring,” Dr. Johnston said. “They do it every day with every patient. It is important today, and will be more important tomorrow.”
 

Reference

Johnston SC. Anticipating and training the physician of the future: The importance of caring in an age of artificial intelligence. Acad Med. 2018;93(8):1105-6. doi: 10.1097/ACM.0000000000002175.

As artificial intelligence (AI) takes on more and more tasks in medical care that mimic human cognition, hospitalists and other physicians will need to adapt to a changing role.

Today AI can identify tuberculosis infections in chest radiographs with almost complete accuracy, diagnose melanoma from images of skin lesions more accurately than dermatologists can, and identify metastatic cells in images of lymph node tissue more accurately than pathologists can. The next 20 years are likely to see further acceleration in the capabilities, according to a recent article by S. Claiborne Johnston, MD, PhD.

“AI will change the practice of medicine. The art of medicine, including all the humanistic components, will only become more important over time. As dean of a medical school, I’m training students who will be practicing in 2065,” Dr. Johnston said. “If I’m not thinking about the future, I’m failing my students and the society they will serve.”

The contributions of AI will shift the emphasis for human caregivers to the caring. Studies have shown that the skills of caring are associated with improved patient outcomes, but most medical schools allocate substantial time in the curriculum to memorization and analysis – tasks that will become less demanding as artificial intelligence improves. The art of caring – communication, empathy, shared decision making, leadership, and team building – is usually a minor part of the medical school curriculum.

Effective leadership and creativity are distant aspirations for artificial intelligence but are growing needs in a system of care that is ever more complex.

At Dr. Johnston’s school, the Dell Medical School at the University of Texas at Austin, they have reduced the duration of basic science instruction to 12 months and emphasized group problem solving, while deemphasizing memorization. This has freed up additional time for instruction in the art of caring, leadership, and creativity.

“Hospitalists should acknowledge the value of caring,” Dr. Johnston said. “They do it every day with every patient. It is important today, and will be more important tomorrow.”
 

Reference

Johnston SC. Anticipating and training the physician of the future: The importance of caring in an age of artificial intelligence. Acad Med. 2018;93(8):1105-6. doi: 10.1097/ACM.0000000000002175.

MIAMI – Researchers are one step closer to developing “drugs for bugs” – agents that target the gut microbiome to prevent and treat cardiometabolic diseases, Stanley L. Hazen, MD, PhD, said at the 2019 Gut Microbiota for Health World Summit.

ShaneKato/E+/Getty Images

“Each person experiences a meal differently through the filter of their gut microbiome, which helps explain individual differences in susceptibility to disease,” said Dr. Hazen of Cleveland Clinic. “In the future, our medicine cabinets will have drugs in them that not only affect us, but also target the microbial enzymes that affect levels of metabolites like TMAO.”

Trimethylamine N-oxide (TMAO) is produced by gut bacteria. High levels (in one study, approximately 6.2 micromolar) significantly increase the risk of major adverse cardiovascular events even after controlling for traditional demographic and clinical risk factors. Studies indicate that TMAO alters cholesterol and bile acid metabolism, upregulates inflammatory pathways, and promotes foam cell formation, all of which worsen atherosclerosis. In addition, TMAO increases clotting risk by enhancing platelet reactivity.

“Reducing the amount of animal products in one’s diet helps reduce TMAO levels,” said Dr. Hazen. Certain fish – mainly those found in deep, cold water, such as cod – are high in TMAO. However, a bigger culprit in the United States is red meat, which contains two major TMAO precursors – choline and carnitine. In a recent study, Dr. Hazen and his associates gave 113 healthy volunteers three isocaloric diets in random order based on red meat, white meat, or plant-based protein. After 4 weeks, eating the daily equivalent of 8 ounces of steak or two quarter-pound beef patties nearly tripled plasma TMAO levels (P less than .05) from baseline. The white meat and vegetarian diets showed no such effect.

Crucially, the effect of red meat was reversible – TMAO levels fell significantly within 4 weeks after participants stopped consuming red meat. Eating red meat low in saturated fat did not prevent TMAO levels from rising, Dr. Hazen noted at the meeting at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

In a second study, Dr. Hazen and his associates identified a two-step process by which gut bacteria metabolize carnitine to TMAO. The second step was greatly enhanced in individuals who eat red meat, suggesting a possible therapeutic target. In a third study, they found that high TMAO levels in mice fell significantly with a single oral dose of a second-generation inhibitor of trimethylamine lyase, the enzyme used by gut bacteria to convert choline to TMAO. The inhibitory effect was irreversible, did not reduce the viability of commensal microorganisms, and significantly lowered platelet hyperreactivity and clot formation.

Such results are exciting, but “drugs for bugs” will exhibit varying effects depending on which gut species are present at baseline, Dr. Hazen explained. Investigators will need to understand and account for these differences before therapies for the microbiome can enter the clinic. For now, a blood test for TMAO is available and can help clinicians tailor their suggestions on what to eat.

Dr. Hazen disclosed a consulting relationship with Proctor & Gamble, royalties for patents from Proctor & Gamble, Cleveland Heart Lab, and Quest Diagnostics, and research support from AstraZeneca, Pfizer, Roche Diagnostics, and Proctor & Gamble.

MIAMI – Researchers are one step closer to developing “drugs for bugs” – agents that target the gut microbiome to prevent and treat cardiometabolic diseases, Stanley L. Hazen, MD, PhD, said at the 2019 Gut Microbiota for Health World Summit.

ShaneKato/E+/Getty Images

“Each person experiences a meal differently through the filter of their gut microbiome, which helps explain individual differences in susceptibility to disease,” said Dr. Hazen of Cleveland Clinic. “In the future, our medicine cabinets will have drugs in them that not only affect us, but also target the microbial enzymes that affect levels of metabolites like TMAO.”

Trimethylamine N-oxide (TMAO) is produced by gut bacteria. High levels (in one study, approximately 6.2 micromolar) significantly increase the risk of major adverse cardiovascular events even after controlling for traditional demographic and clinical risk factors. Studies indicate that TMAO alters cholesterol and bile acid metabolism, upregulates inflammatory pathways, and promotes foam cell formation, all of which worsen atherosclerosis. In addition, TMAO increases clotting risk by enhancing platelet reactivity.

“Reducing the amount of animal products in one’s diet helps reduce TMAO levels,” said Dr. Hazen. Certain fish – mainly those found in deep, cold water, such as cod – are high in TMAO. However, a bigger culprit in the United States is red meat, which contains two major TMAO precursors – choline and carnitine. In a recent study, Dr. Hazen and his associates gave 113 healthy volunteers three isocaloric diets in random order based on red meat, white meat, or plant-based protein. After 4 weeks, eating the daily equivalent of 8 ounces of steak or two quarter-pound beef patties nearly tripled plasma TMAO levels (P less than .05) from baseline. The white meat and vegetarian diets showed no such effect.

Crucially, the effect of red meat was reversible – TMAO levels fell significantly within 4 weeks after participants stopped consuming red meat. Eating red meat low in saturated fat did not prevent TMAO levels from rising, Dr. Hazen noted at the meeting at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

In a second study, Dr. Hazen and his associates identified a two-step process by which gut bacteria metabolize carnitine to TMAO. The second step was greatly enhanced in individuals who eat red meat, suggesting a possible therapeutic target. In a third study, they found that high TMAO levels in mice fell significantly with a single oral dose of a second-generation inhibitor of trimethylamine lyase, the enzyme used by gut bacteria to convert choline to TMAO. The inhibitory effect was irreversible, did not reduce the viability of commensal microorganisms, and significantly lowered platelet hyperreactivity and clot formation.

Such results are exciting, but “drugs for bugs” will exhibit varying effects depending on which gut species are present at baseline, Dr. Hazen explained. Investigators will need to understand and account for these differences before therapies for the microbiome can enter the clinic. For now, a blood test for TMAO is available and can help clinicians tailor their suggestions on what to eat.

Dr. Hazen disclosed a consulting relationship with Proctor & Gamble, royalties for patents from Proctor & Gamble, Cleveland Heart Lab, and Quest Diagnostics, and research support from AstraZeneca, Pfizer, Roche Diagnostics, and Proctor & Gamble.

MIAMI – Researchers are one step closer to developing “drugs for bugs” – agents that target the gut microbiome to prevent and treat cardiometabolic diseases, Stanley L. Hazen, MD, PhD, said at the 2019 Gut Microbiota for Health World Summit.

ShaneKato/E+/Getty Images

“Each person experiences a meal differently through the filter of their gut microbiome, which helps explain individual differences in susceptibility to disease,” said Dr. Hazen of Cleveland Clinic. “In the future, our medicine cabinets will have drugs in them that not only affect us, but also target the microbial enzymes that affect levels of metabolites like TMAO.”

Trimethylamine N-oxide (TMAO) is produced by gut bacteria. High levels (in one study, approximately 6.2 micromolar) significantly increase the risk of major adverse cardiovascular events even after controlling for traditional demographic and clinical risk factors. Studies indicate that TMAO alters cholesterol and bile acid metabolism, upregulates inflammatory pathways, and promotes foam cell formation, all of which worsen atherosclerosis. In addition, TMAO increases clotting risk by enhancing platelet reactivity.

“Reducing the amount of animal products in one’s diet helps reduce TMAO levels,” said Dr. Hazen. Certain fish – mainly those found in deep, cold water, such as cod – are high in TMAO. However, a bigger culprit in the United States is red meat, which contains two major TMAO precursors – choline and carnitine. In a recent study, Dr. Hazen and his associates gave 113 healthy volunteers three isocaloric diets in random order based on red meat, white meat, or plant-based protein. After 4 weeks, eating the daily equivalent of 8 ounces of steak or two quarter-pound beef patties nearly tripled plasma TMAO levels (P less than .05) from baseline. The white meat and vegetarian diets showed no such effect.

Crucially, the effect of red meat was reversible – TMAO levels fell significantly within 4 weeks after participants stopped consuming red meat. Eating red meat low in saturated fat did not prevent TMAO levels from rising, Dr. Hazen noted at the meeting at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

In a second study, Dr. Hazen and his associates identified a two-step process by which gut bacteria metabolize carnitine to TMAO. The second step was greatly enhanced in individuals who eat red meat, suggesting a possible therapeutic target. In a third study, they found that high TMAO levels in mice fell significantly with a single oral dose of a second-generation inhibitor of trimethylamine lyase, the enzyme used by gut bacteria to convert choline to TMAO. The inhibitory effect was irreversible, did not reduce the viability of commensal microorganisms, and significantly lowered platelet hyperreactivity and clot formation.

Such results are exciting, but “drugs for bugs” will exhibit varying effects depending on which gut species are present at baseline, Dr. Hazen explained. Investigators will need to understand and account for these differences before therapies for the microbiome can enter the clinic. For now, a blood test for TMAO is available and can help clinicians tailor their suggestions on what to eat.

Dr. Hazen disclosed a consulting relationship with Proctor & Gamble, royalties for patents from Proctor & Gamble, Cleveland Heart Lab, and Quest Diagnostics, and research support from AstraZeneca, Pfizer, Roche Diagnostics, and Proctor & Gamble.