A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A systematic review of nutritional supplements for hair loss finds that a wide range of the products have potential but that the studies could not provide definitive evidence of safety and effectiveness because of small sample sizes, heterogeneity of hair loss types in study subjects, or other limitations.

The review, published online in JAMA Dermatology, notes that “Twelve of the 20 nutritional interventions had high-quality studies suggesting objectively evaluated effectiveness.”

It is “ground breaking,” in part because of its breadth and depth, said Eva Simmons-O’Brien, MD, a dermatologist in Towson, Md., who often recommends supplements for her patients with hair loss. “It basically kind of vindicates what some of us have been doing for a number of years in terms of treating hair loss,” she told this news organization. “It should hopefully make it more commonplace for dermatologists to consider using nutritional supplements as an adjuvant to treating hair loss,” added Dr. Simmons-O’Brien.

The review “is very helpful,” agreed Lynne J. Goldberg, MD, professor of dermatology and pathology and laboratory medicine at Boston University. Dr. Goldberg noted that many patients are already taking supplements and want to know whether they are safe and effective. The review “points out what the problems are; it talks about what the individual ingredients are and what they do, what the problems are; and it concluded that some people may find these helpful. Which is exactly what I tell my patients,” said Dr. Goldberg, who is also director of the Hair Clinic at Boston Medical Center.

“For patients who are highly motivated and eager to try this, we’re hoping that this systematic review serves as a foundation to have a conversation,” study coauthor Arash Mostaghimi, MD, MPA, MPH, of the department of dermatology at Harvard Medical School, told this news organization. “When there’s medical uncertainty and the question is how much risk is one willing to take, the most important thing to do is to present the data and engage in shared decision-making with the patient,” noted Dr. Mostaghimi, who is also director of the inpatient dermatology consult service at Brigham and Women’s Hospital, Boston.
 

Surprising effectiveness

Going into the study, “we felt it would be likely that majority of nutritional supplements would either not be effective or not studied,” he said.

Dr. Mostaghimi and his coauthors conducted the study because so many patients take nutritional supplements to address hair loss, he said. An initial literature survey yielded more than 6,300 citations, but after screening and reviews, the authors included 30 articles for evaluation.

The review begins with a look at studies of saw palmetto (Serenoa repens), a botanical compound thought to inhibit the enzyme 5-alpha reductase (5AR), which converts testosterone to dihydroxytestosterone (DHT). DHT is a mediator of androgenic alopecia (AGA). The studies suggest that the compound might stabilize hair loss, “although its effect is likely less than that of finasteride,” write the authors. They also note that side effects associated with finasteride, such as sexual dysfunction, were also observed with saw palmetto “but to a lesser extent.”

For AGA, pumpkin seed oil may also be effective and a “potential alternative” to finasteride for AGA, and Forti5, a nutritional supplement that includes botanical 5AR inhibitors and other ingredients, had favorable effects in one study, the authors write. But neither has been compared to finasteride, and the Forti5 study lacked a control group.

The review also examines the micronutrients vitamin D, zinc, B vitamins, and antioxidants. Low levels of vitamin D have been associated with alopecia areata (AA), AGA, and telogen effluvium (TE) in some studies, and zinc deficiencies have been associated with TE, hair breakage, and thinning, according to the review. A single-arm vitamin D study showed improved results at 6 months for women with TE, but there was no control group and TE is self-resolving, the authors add. Studies in patients with normal zinc levels at baseline who had AA or hair loss showed significant hair regrowth and increased hair thickness and density, but the trials were a mishmash of controls and no controls and relied on self-perceived hair-loss data.

Larger more rigorous studies should be done to evaluate zinc’s effectiveness with AA, the authors comment.

Many patients take vitamin B7 (biotin) for hair loss. It has not been studied on its own but was an ingredient in some supplements in the review. Dr. Simmons-O’Brien said that biotin won’t result in new hair growth but that it can help strengthen the new hairs that grow as a result of other therapies. Both she and the study authors note that the Food and Drug Administration has warned against biotin supplementation because it can interfere with troponin and other test results.

The review also finds that immunomodulators –such as Chinese herbal extracts from paeony and glycyrrhizin – were effective in severe AA. Growth hormone modulators targeting deficiencies in insulin growth factor 1 or growth hormone are also promising. Studies of the modulators capsaicin and isoflavones – used topically – spurred hair growth, the authors write.

Products containing marine protein supplements, including Viviscal and Nourkrin, appeared effective in increasing hair counts in men and women, but the studies were funded by the manufacturer and were not well controlled. Side effects with Viviscal included bloating, according to the review.

The multi-ingredient supplements Nutrafol, Omni-Three, Apple Nutraceutical, and Lambdapil were also included in the review. Only Omni-Three showed no effectiveness, but studies of the other supplements had various limitations, including lack of controls and small sample sizes.
 

Complicated problem, multiple solutions

Given the many reasons for hair loss, multiple solutions are needed, the dermatologists note.

Dr. Mostaghimi said that he’s still a bit skeptical that supplements work as consistently as described or as well as described, given that he and his coauthors were unable to find any negative studies. In talking with patients who are taking supplements, he said that his first aim is to make sure they are safe. At least the supplements in the review have been studied for safety, he added.

He will encourage replacement of vitamin D or zinc or other vitamins or minerals if patients are deficient but said that he does not “actively encourage supplementation.”

Dr. Simmons-O’Brien said that, when evaluating patients with hair loss, she orders lab tests to determine whether the patient has anemia or a thyroid issue or deficiencies in vitamins or minerals or other nutritional deficiencies, asks about diet and styling practices, and takes a scalp biopsy. It is not uncommon to recommend supplementation on the basis of those findings, she added.

“As a hair-loss specialist, my job is to treat the patient at their level, in their framework, in their comfort zone,” said Dr. Goldberg. Some patients don’t want to take medications for hair loss, so she might recommend supplements in those cases but tells patients that they aren’t well studied.

She added that it can be hard to tell whether a supplement is working, particularly if it has multiple ingredients.

Dr. Mostaghimi reported consulting fees from Pfizer, Concert, Lilly, Hims and Hers, Equillium, AbbVie, Digital Diagnostics, and Bioniz and grants from Pfizer, all outside the submitted work. In addition, Dr. Mostaghimi disclosed that he is an associate editor of JAMA Dermatology but was not involved in any of the decisions regarding the review of the manuscript or its acceptance. No other disclosures were reported by the other study authors. Dr. Goldberg reported no disclosures. Dr. Simmons-O›Brien is a medical consultant for Isdin, but not for hair products.

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

A systematic review of nutritional supplements for hair loss finds that a wide range of the products have potential but that the studies could not provide definitive evidence of safety and effectiveness because of small sample sizes, heterogeneity of hair loss types in study subjects, or other limitations.

The review, published online in JAMA Dermatology, notes that “Twelve of the 20 nutritional interventions had high-quality studies suggesting objectively evaluated effectiveness.”

It is “ground breaking,” in part because of its breadth and depth, said Eva Simmons-O’Brien, MD, a dermatologist in Towson, Md., who often recommends supplements for her patients with hair loss. “It basically kind of vindicates what some of us have been doing for a number of years in terms of treating hair loss,” she told this news organization. “It should hopefully make it more commonplace for dermatologists to consider using nutritional supplements as an adjuvant to treating hair loss,” added Dr. Simmons-O’Brien.

The review “is very helpful,” agreed Lynne J. Goldberg, MD, professor of dermatology and pathology and laboratory medicine at Boston University. Dr. Goldberg noted that many patients are already taking supplements and want to know whether they are safe and effective. The review “points out what the problems are; it talks about what the individual ingredients are and what they do, what the problems are; and it concluded that some people may find these helpful. Which is exactly what I tell my patients,” said Dr. Goldberg, who is also director of the Hair Clinic at Boston Medical Center.

“For patients who are highly motivated and eager to try this, we’re hoping that this systematic review serves as a foundation to have a conversation,” study coauthor Arash Mostaghimi, MD, MPA, MPH, of the department of dermatology at Harvard Medical School, told this news organization. “When there’s medical uncertainty and the question is how much risk is one willing to take, the most important thing to do is to present the data and engage in shared decision-making with the patient,” noted Dr. Mostaghimi, who is also director of the inpatient dermatology consult service at Brigham and Women’s Hospital, Boston.
 

Surprising effectiveness

Going into the study, “we felt it would be likely that majority of nutritional supplements would either not be effective or not studied,” he said.

Dr. Mostaghimi and his coauthors conducted the study because so many patients take nutritional supplements to address hair loss, he said. An initial literature survey yielded more than 6,300 citations, but after screening and reviews, the authors included 30 articles for evaluation.

The review begins with a look at studies of saw palmetto (Serenoa repens), a botanical compound thought to inhibit the enzyme 5-alpha reductase (5AR), which converts testosterone to dihydroxytestosterone (DHT). DHT is a mediator of androgenic alopecia (AGA). The studies suggest that the compound might stabilize hair loss, “although its effect is likely less than that of finasteride,” write the authors. They also note that side effects associated with finasteride, such as sexual dysfunction, were also observed with saw palmetto “but to a lesser extent.”

For AGA, pumpkin seed oil may also be effective and a “potential alternative” to finasteride for AGA, and Forti5, a nutritional supplement that includes botanical 5AR inhibitors and other ingredients, had favorable effects in one study, the authors write. But neither has been compared to finasteride, and the Forti5 study lacked a control group.

The review also examines the micronutrients vitamin D, zinc, B vitamins, and antioxidants. Low levels of vitamin D have been associated with alopecia areata (AA), AGA, and telogen effluvium (TE) in some studies, and zinc deficiencies have been associated with TE, hair breakage, and thinning, according to the review. A single-arm vitamin D study showed improved results at 6 months for women with TE, but there was no control group and TE is self-resolving, the authors add. Studies in patients with normal zinc levels at baseline who had AA or hair loss showed significant hair regrowth and increased hair thickness and density, but the trials were a mishmash of controls and no controls and relied on self-perceived hair-loss data.

Larger more rigorous studies should be done to evaluate zinc’s effectiveness with AA, the authors comment.

Many patients take vitamin B7 (biotin) for hair loss. It has not been studied on its own but was an ingredient in some supplements in the review. Dr. Simmons-O’Brien said that biotin won’t result in new hair growth but that it can help strengthen the new hairs that grow as a result of other therapies. Both she and the study authors note that the Food and Drug Administration has warned against biotin supplementation because it can interfere with troponin and other test results.

The review also finds that immunomodulators –such as Chinese herbal extracts from paeony and glycyrrhizin – were effective in severe AA. Growth hormone modulators targeting deficiencies in insulin growth factor 1 or growth hormone are also promising. Studies of the modulators capsaicin and isoflavones – used topically – spurred hair growth, the authors write.

Products containing marine protein supplements, including Viviscal and Nourkrin, appeared effective in increasing hair counts in men and women, but the studies were funded by the manufacturer and were not well controlled. Side effects with Viviscal included bloating, according to the review.

The multi-ingredient supplements Nutrafol, Omni-Three, Apple Nutraceutical, and Lambdapil were also included in the review. Only Omni-Three showed no effectiveness, but studies of the other supplements had various limitations, including lack of controls and small sample sizes.
 

Complicated problem, multiple solutions

Given the many reasons for hair loss, multiple solutions are needed, the dermatologists note.

Dr. Mostaghimi said that he’s still a bit skeptical that supplements work as consistently as described or as well as described, given that he and his coauthors were unable to find any negative studies. In talking with patients who are taking supplements, he said that his first aim is to make sure they are safe. At least the supplements in the review have been studied for safety, he added.

He will encourage replacement of vitamin D or zinc or other vitamins or minerals if patients are deficient but said that he does not “actively encourage supplementation.”

Dr. Simmons-O’Brien said that, when evaluating patients with hair loss, she orders lab tests to determine whether the patient has anemia or a thyroid issue or deficiencies in vitamins or minerals or other nutritional deficiencies, asks about diet and styling practices, and takes a scalp biopsy. It is not uncommon to recommend supplementation on the basis of those findings, she added.

“As a hair-loss specialist, my job is to treat the patient at their level, in their framework, in their comfort zone,” said Dr. Goldberg. Some patients don’t want to take medications for hair loss, so she might recommend supplements in those cases but tells patients that they aren’t well studied.

She added that it can be hard to tell whether a supplement is working, particularly if it has multiple ingredients.

Dr. Mostaghimi reported consulting fees from Pfizer, Concert, Lilly, Hims and Hers, Equillium, AbbVie, Digital Diagnostics, and Bioniz and grants from Pfizer, all outside the submitted work. In addition, Dr. Mostaghimi disclosed that he is an associate editor of JAMA Dermatology but was not involved in any of the decisions regarding the review of the manuscript or its acceptance. No other disclosures were reported by the other study authors. Dr. Goldberg reported no disclosures. Dr. Simmons-O›Brien is a medical consultant for Isdin, but not for hair products.

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

A systematic review of nutritional supplements for hair loss finds that a wide range of the products have potential but that the studies could not provide definitive evidence of safety and effectiveness because of small sample sizes, heterogeneity of hair loss types in study subjects, or other limitations.

The review, published online in JAMA Dermatology, notes that “Twelve of the 20 nutritional interventions had high-quality studies suggesting objectively evaluated effectiveness.”

It is “ground breaking,” in part because of its breadth and depth, said Eva Simmons-O’Brien, MD, a dermatologist in Towson, Md., who often recommends supplements for her patients with hair loss. “It basically kind of vindicates what some of us have been doing for a number of years in terms of treating hair loss,” she told this news organization. “It should hopefully make it more commonplace for dermatologists to consider using nutritional supplements as an adjuvant to treating hair loss,” added Dr. Simmons-O’Brien.

The review “is very helpful,” agreed Lynne J. Goldberg, MD, professor of dermatology and pathology and laboratory medicine at Boston University. Dr. Goldberg noted that many patients are already taking supplements and want to know whether they are safe and effective. The review “points out what the problems are; it talks about what the individual ingredients are and what they do, what the problems are; and it concluded that some people may find these helpful. Which is exactly what I tell my patients,” said Dr. Goldberg, who is also director of the Hair Clinic at Boston Medical Center.

“For patients who are highly motivated and eager to try this, we’re hoping that this systematic review serves as a foundation to have a conversation,” study coauthor Arash Mostaghimi, MD, MPA, MPH, of the department of dermatology at Harvard Medical School, told this news organization. “When there’s medical uncertainty and the question is how much risk is one willing to take, the most important thing to do is to present the data and engage in shared decision-making with the patient,” noted Dr. Mostaghimi, who is also director of the inpatient dermatology consult service at Brigham and Women’s Hospital, Boston.
 

Surprising effectiveness

Going into the study, “we felt it would be likely that majority of nutritional supplements would either not be effective or not studied,” he said.

Dr. Mostaghimi and his coauthors conducted the study because so many patients take nutritional supplements to address hair loss, he said. An initial literature survey yielded more than 6,300 citations, but after screening and reviews, the authors included 30 articles for evaluation.

The review begins with a look at studies of saw palmetto (Serenoa repens), a botanical compound thought to inhibit the enzyme 5-alpha reductase (5AR), which converts testosterone to dihydroxytestosterone (DHT). DHT is a mediator of androgenic alopecia (AGA). The studies suggest that the compound might stabilize hair loss, “although its effect is likely less than that of finasteride,” write the authors. They also note that side effects associated with finasteride, such as sexual dysfunction, were also observed with saw palmetto “but to a lesser extent.”

For AGA, pumpkin seed oil may also be effective and a “potential alternative” to finasteride for AGA, and Forti5, a nutritional supplement that includes botanical 5AR inhibitors and other ingredients, had favorable effects in one study, the authors write. But neither has been compared to finasteride, and the Forti5 study lacked a control group.

The review also examines the micronutrients vitamin D, zinc, B vitamins, and antioxidants. Low levels of vitamin D have been associated with alopecia areata (AA), AGA, and telogen effluvium (TE) in some studies, and zinc deficiencies have been associated with TE, hair breakage, and thinning, according to the review. A single-arm vitamin D study showed improved results at 6 months for women with TE, but there was no control group and TE is self-resolving, the authors add. Studies in patients with normal zinc levels at baseline who had AA or hair loss showed significant hair regrowth and increased hair thickness and density, but the trials were a mishmash of controls and no controls and relied on self-perceived hair-loss data.

Larger more rigorous studies should be done to evaluate zinc’s effectiveness with AA, the authors comment.

Many patients take vitamin B7 (biotin) for hair loss. It has not been studied on its own but was an ingredient in some supplements in the review. Dr. Simmons-O’Brien said that biotin won’t result in new hair growth but that it can help strengthen the new hairs that grow as a result of other therapies. Both she and the study authors note that the Food and Drug Administration has warned against biotin supplementation because it can interfere with troponin and other test results.

The review also finds that immunomodulators –such as Chinese herbal extracts from paeony and glycyrrhizin – were effective in severe AA. Growth hormone modulators targeting deficiencies in insulin growth factor 1 or growth hormone are also promising. Studies of the modulators capsaicin and isoflavones – used topically – spurred hair growth, the authors write.

Products containing marine protein supplements, including Viviscal and Nourkrin, appeared effective in increasing hair counts in men and women, but the studies were funded by the manufacturer and were not well controlled. Side effects with Viviscal included bloating, according to the review.

The multi-ingredient supplements Nutrafol, Omni-Three, Apple Nutraceutical, and Lambdapil were also included in the review. Only Omni-Three showed no effectiveness, but studies of the other supplements had various limitations, including lack of controls and small sample sizes.
 

Complicated problem, multiple solutions

Given the many reasons for hair loss, multiple solutions are needed, the dermatologists note.

Dr. Mostaghimi said that he’s still a bit skeptical that supplements work as consistently as described or as well as described, given that he and his coauthors were unable to find any negative studies. In talking with patients who are taking supplements, he said that his first aim is to make sure they are safe. At least the supplements in the review have been studied for safety, he added.

He will encourage replacement of vitamin D or zinc or other vitamins or minerals if patients are deficient but said that he does not “actively encourage supplementation.”

Dr. Simmons-O’Brien said that, when evaluating patients with hair loss, she orders lab tests to determine whether the patient has anemia or a thyroid issue or deficiencies in vitamins or minerals or other nutritional deficiencies, asks about diet and styling practices, and takes a scalp biopsy. It is not uncommon to recommend supplementation on the basis of those findings, she added.

“As a hair-loss specialist, my job is to treat the patient at their level, in their framework, in their comfort zone,” said Dr. Goldberg. Some patients don’t want to take medications for hair loss, so she might recommend supplements in those cases but tells patients that they aren’t well studied.

She added that it can be hard to tell whether a supplement is working, particularly if it has multiple ingredients.

Dr. Mostaghimi reported consulting fees from Pfizer, Concert, Lilly, Hims and Hers, Equillium, AbbVie, Digital Diagnostics, and Bioniz and grants from Pfizer, all outside the submitted work. In addition, Dr. Mostaghimi disclosed that he is an associate editor of JAMA Dermatology but was not involved in any of the decisions regarding the review of the manuscript or its acceptance. No other disclosures were reported by the other study authors. Dr. Goldberg reported no disclosures. Dr. Simmons-O›Brien is a medical consultant for Isdin, but not for hair products.

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

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

The study is published in the Journal of the American College of Cardiology and was also published online.

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

The study is published in the Journal of the American College of Cardiology and was also published online.

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

The study is published in the Journal of the American College of Cardiology and was also published online.

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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

The Diagnosis: Hybrid Schwannoma-Perineurioma

Hybrid nerve sheath tumors are rare entities that display features of more than one nerve sheath tumor such as neurofibromas, schwannomas, and perineuriomas.¹ These tumors often are found in the dermis or subcutaneous tissue of the extremities and abdomen²; however, cases of hybrid peripheral nerve sheath tumors have been reported in many anatomical locations without a gender predilection.³ The most common type of hybrid nerve sheath tumor is a schwannoma-perineurioma.^3,4 Histologically, they are well-circumscribed lesions composed of both spindled Schwann cells with plump nuclei and spindled perineural cells with more elongated thin nuclei.⁵ Although the Schwann cell component tends to predominate, the 2 cell populations interdigitate, making it challenging to definitively distinguish them by hematoxylin and eosin staining alone.4 However, immunohistochemical (IHC) staining can be used to help distinguish the 2 separate cell populations. Staining for S-100 and SRY-box transcription factor 10 (SOX-10) will be positive in the Schwann cell component, and staining for epithelial membrane antigen, Claudin-1, or glucose transporter-1 (Figure 1) will be positive in the perineural component. Other hybrid forms of benign nerve sheath tumors include neurofibroma-schwannoma and neurofibromaperineurioma.⁴ Neurofibroma-schwannomas usually have a schwannoma component containing Antoni A areas with palisading Verocay bodies. The neurofibroma cells typically have wavy elongated nuclei, fibroblasts, and mucinous myxoid material.³ Neurofibroma-perineurioma is the least common hybrid tumor. These hybrid tumors have a plexiform neurofibroma appearance with areas of perineural differentiation, which can be difficult to identify on routine histology and typically will require IHC staining to appreciate. The neurofibroma component will stain positive for S-100 and negative for markers of perineural differentiation, including epithelial membrane antigen, glucose transporter-1, and Claudin-1.³ Although schwannoma-perineuriomas are benign sporadic tumors not associated with neurofibromatosis, neurofibromaschwannomas are associated with neurofibromatosis types 1 and 2 (NF1 and NF2). Neurofibroma-perineurioma tumors usually are associated with only NF1.^3,6

Schwannomas typically present in middle-aged patients as tumors located on flexor surfaces.⁷ Although perineural cells can be seen at the periphery of a schwannoma forming a capsule, they do not interdigitate between the Schwann cells. Schwannomas are composed almost entirely of well-differentiated Schwann cells.^1,4,8 Schwannomas classically are well-circumscribed, encapsulated, biphasic lesions with alternating compact areas (Antoni A) and loosely arranged areas (Antoni B). The spindled cells occasionally may display nuclear palisading within the Antoni A areas, known as Verocay bodies (Figure 2). Antoni B areas are more disorganized and hypocellular with variable macrophage infiltrate.^1,4,8 The Schwann cells predominantly will have bland cytologic features, but scattered areas of degenerative nuclear atypia (also known as ancient change) may be present.⁴ Multiple schwannomas are associated with NF2 gene mutations and loss of merlin protein.8 There are different subtypes of schwannomas, including cellular and plexiform schwannomas.⁴ Because schwannomas are benign nerve sheath lesions, treatment typically consists of excision with careful dissection around the involved nerve.⁹

Neurofibromas are the most common peripheral nerve sheath tumors of the skin with no notable anatomic prediction, though one study found them to be more prevalent in the upper extremities.¹⁰ They typically present as sporadic solitary lesions, but multiple lesions may appear as superficial pedunculated growths that present in those aged 20 to 30 years.¹¹ Microscopically, neurofibromas typically are not well circumscribed and have an infiltrative growth pattern. Neurofibromas are composed of cytologically bland spindled Schwann cells with thin wavy nuclei in a variable myxoid stroma (Figure 3). In addition to Schwann cells, neurofibromas contain other cell components, including fibroblasts, mast cells, perineurial-like cells, and residual axons.⁴ Neurofibromas typically are located in the dermis but may extend into the subcutaneous tissue. Clinically, the overlying skin may show hyperpigmentation.8 Neurofibromas can be localized, diffuse, or plexiform, with the majority being localized. Diffuse neurofibromas clinically have a raised plaque appearance. Treatment is unnecessary because these lesions are benign.⁷

Desmoplastic melanoma (DM) is another diagnosis in the differential for this case. Patients with DM are older compared to non-DM melanoma patients, with a male predilection.¹² Desmoplastic melanomas are more likely to be located on the head and neck. In approximately one-third of cases, no in situ component will be identified, leading to confusion of the dermal lesion as a neural lesion or an area of scar formation. Microscopically, DM presents as a variable cellular infiltrative tumor composed of spindle cells with varying degrees of nuclear atypia. The spindled melanocytes are within a collagenous (desmoplastic) stroma (Figure 4).¹³ Desmoplastic melanoma has been described with a low mitotic index, leading to misdiagnosis with benign spindle cell neoplasms.¹⁴ The spindle cells should be positive for S-100 and SOX-10 with IHC staining. Unlike other melanomas, human melanoma black 45 and Melan-A often are negative or only focally positive. Treatment of DM is similar to non-DM in that wide local excision usually is employed. A systematic review evaluating sentinel lymph node biopsy (SLNB) recommended consideration of SLNB in mixed DM but not for pure DM, as rates of positive SLNB were much lower in the latter.¹⁵

Patients with malignant peripheral nerve sheath tumor (MPNST) usually present with an enlarging mass, pain, or neurologic symptoms. Most cases of MPNST are located on the trunk or extremities.¹⁶ Plexiform neurofibromas, especially in adults with NF1, have the potential to transform into an MPNST.⁴ In fact, MPNST is the most common malignancy in patients with NF1.¹⁷ Pediatric cancer survivors also are predisposed to MPNST, with a 40-fold increase in incidence compared to the general population.¹⁸ Transformation from schwannoma to MPNST is rare but has been reported.⁸ Histologically, spindle cells easily can be appreciated with a fasciculated growth pattern (Figure 5). Mitotic activity and tumor necrosis may be present. Diagnosis of these tumors historically has been challenging, though recent research has identified inactivation of polycomb repressive complex 2 in 70% to 90% of MPNSTs. Because of polycomb repressive complex 2 inactivation, there is loss of stone H3K27 trimethylation that can be capitalized on for MPNST diagnosis.¹⁹ Negative IHC staining for H3K27 trimethylation has been found to be highly specific for MPNST. Negative staining for different cytokeratin and melanoma markers can be helpful in differentiating it from carcinomas and melanoma. The only curative treatment for MPNST is complete excision, leaving patients with recurrent, refractory, and metastatic cases to be encouraged for enrollment in clinical trials. The 5-year survival rates for patients with MPNST reported in the literature range from 20% to 50%.²⁰

The Diagnosis: Hybrid Schwannoma-Perineurioma

Hybrid nerve sheath tumors are rare entities that display features of more than one nerve sheath tumor such as neurofibromas, schwannomas, and perineuriomas.¹ These tumors often are found in the dermis or subcutaneous tissue of the extremities and abdomen²; however, cases of hybrid peripheral nerve sheath tumors have been reported in many anatomical locations without a gender predilection.³ The most common type of hybrid nerve sheath tumor is a schwannoma-perineurioma.^3,4 Histologically, they are well-circumscribed lesions composed of both spindled Schwann cells with plump nuclei and spindled perineural cells with more elongated thin nuclei.⁵ Although the Schwann cell component tends to predominate, the 2 cell populations interdigitate, making it challenging to definitively distinguish them by hematoxylin and eosin staining alone.4 However, immunohistochemical (IHC) staining can be used to help distinguish the 2 separate cell populations. Staining for S-100 and SRY-box transcription factor 10 (SOX-10) will be positive in the Schwann cell component, and staining for epithelial membrane antigen, Claudin-1, or glucose transporter-1 (Figure 1) will be positive in the perineural component. Other hybrid forms of benign nerve sheath tumors include neurofibroma-schwannoma and neurofibromaperineurioma.⁴ Neurofibroma-schwannomas usually have a schwannoma component containing Antoni A areas with palisading Verocay bodies. The neurofibroma cells typically have wavy elongated nuclei, fibroblasts, and mucinous myxoid material.³ Neurofibroma-perineurioma is the least common hybrid tumor. These hybrid tumors have a plexiform neurofibroma appearance with areas of perineural differentiation, which can be difficult to identify on routine histology and typically will require IHC staining to appreciate. The neurofibroma component will stain positive for S-100 and negative for markers of perineural differentiation, including epithelial membrane antigen, glucose transporter-1, and Claudin-1.³ Although schwannoma-perineuriomas are benign sporadic tumors not associated with neurofibromatosis, neurofibromaschwannomas are associated with neurofibromatosis types 1 and 2 (NF1 and NF2). Neurofibroma-perineurioma tumors usually are associated with only NF1.^3,6

Schwannomas typically present in middle-aged patients as tumors located on flexor surfaces.⁷ Although perineural cells can be seen at the periphery of a schwannoma forming a capsule, they do not interdigitate between the Schwann cells. Schwannomas are composed almost entirely of well-differentiated Schwann cells.^1,4,8 Schwannomas classically are well-circumscribed, encapsulated, biphasic lesions with alternating compact areas (Antoni A) and loosely arranged areas (Antoni B). The spindled cells occasionally may display nuclear palisading within the Antoni A areas, known as Verocay bodies (Figure 2). Antoni B areas are more disorganized and hypocellular with variable macrophage infiltrate.^1,4,8 The Schwann cells predominantly will have bland cytologic features, but scattered areas of degenerative nuclear atypia (also known as ancient change) may be present.⁴ Multiple schwannomas are associated with NF2 gene mutations and loss of merlin protein.8 There are different subtypes of schwannomas, including cellular and plexiform schwannomas.⁴ Because schwannomas are benign nerve sheath lesions, treatment typically consists of excision with careful dissection around the involved nerve.⁹

Neurofibromas are the most common peripheral nerve sheath tumors of the skin with no notable anatomic prediction, though one study found them to be more prevalent in the upper extremities.¹⁰ They typically present as sporadic solitary lesions, but multiple lesions may appear as superficial pedunculated growths that present in those aged 20 to 30 years.¹¹ Microscopically, neurofibromas typically are not well circumscribed and have an infiltrative growth pattern. Neurofibromas are composed of cytologically bland spindled Schwann cells with thin wavy nuclei in a variable myxoid stroma (Figure 3). In addition to Schwann cells, neurofibromas contain other cell components, including fibroblasts, mast cells, perineurial-like cells, and residual axons.⁴ Neurofibromas typically are located in the dermis but may extend into the subcutaneous tissue. Clinically, the overlying skin may show hyperpigmentation.8 Neurofibromas can be localized, diffuse, or plexiform, with the majority being localized. Diffuse neurofibromas clinically have a raised plaque appearance. Treatment is unnecessary because these lesions are benign.⁷

Desmoplastic melanoma (DM) is another diagnosis in the differential for this case. Patients with DM are older compared to non-DM melanoma patients, with a male predilection.¹² Desmoplastic melanomas are more likely to be located on the head and neck. In approximately one-third of cases, no in situ component will be identified, leading to confusion of the dermal lesion as a neural lesion or an area of scar formation. Microscopically, DM presents as a variable cellular infiltrative tumor composed of spindle cells with varying degrees of nuclear atypia. The spindled melanocytes are within a collagenous (desmoplastic) stroma (Figure 4).¹³ Desmoplastic melanoma has been described with a low mitotic index, leading to misdiagnosis with benign spindle cell neoplasms.¹⁴ The spindle cells should be positive for S-100 and SOX-10 with IHC staining. Unlike other melanomas, human melanoma black 45 and Melan-A often are negative or only focally positive. Treatment of DM is similar to non-DM in that wide local excision usually is employed. A systematic review evaluating sentinel lymph node biopsy (SLNB) recommended consideration of SLNB in mixed DM but not for pure DM, as rates of positive SLNB were much lower in the latter.¹⁵

Patients with malignant peripheral nerve sheath tumor (MPNST) usually present with an enlarging mass, pain, or neurologic symptoms. Most cases of MPNST are located on the trunk or extremities.¹⁶ Plexiform neurofibromas, especially in adults with NF1, have the potential to transform into an MPNST.⁴ In fact, MPNST is the most common malignancy in patients with NF1.¹⁷ Pediatric cancer survivors also are predisposed to MPNST, with a 40-fold increase in incidence compared to the general population.¹⁸ Transformation from schwannoma to MPNST is rare but has been reported.⁸ Histologically, spindle cells easily can be appreciated with a fasciculated growth pattern (Figure 5). Mitotic activity and tumor necrosis may be present. Diagnosis of these tumors historically has been challenging, though recent research has identified inactivation of polycomb repressive complex 2 in 70% to 90% of MPNSTs. Because of polycomb repressive complex 2 inactivation, there is loss of stone H3K27 trimethylation that can be capitalized on for MPNST diagnosis.¹⁹ Negative IHC staining for H3K27 trimethylation has been found to be highly specific for MPNST. Negative staining for different cytokeratin and melanoma markers can be helpful in differentiating it from carcinomas and melanoma. The only curative treatment for MPNST is complete excision, leaving patients with recurrent, refractory, and metastatic cases to be encouraged for enrollment in clinical trials. The 5-year survival rates for patients with MPNST reported in the literature range from 20% to 50%.²⁰

The Diagnosis: Hybrid Schwannoma-Perineurioma

Hybrid nerve sheath tumors are rare entities that display features of more than one nerve sheath tumor such as neurofibromas, schwannomas, and perineuriomas.¹ These tumors often are found in the dermis or subcutaneous tissue of the extremities and abdomen²; however, cases of hybrid peripheral nerve sheath tumors have been reported in many anatomical locations without a gender predilection.³ The most common type of hybrid nerve sheath tumor is a schwannoma-perineurioma.^3,4 Histologically, they are well-circumscribed lesions composed of both spindled Schwann cells with plump nuclei and spindled perineural cells with more elongated thin nuclei.⁵ Although the Schwann cell component tends to predominate, the 2 cell populations interdigitate, making it challenging to definitively distinguish them by hematoxylin and eosin staining alone.4 However, immunohistochemical (IHC) staining can be used to help distinguish the 2 separate cell populations. Staining for S-100 and SRY-box transcription factor 10 (SOX-10) will be positive in the Schwann cell component, and staining for epithelial membrane antigen, Claudin-1, or glucose transporter-1 (Figure 1) will be positive in the perineural component. Other hybrid forms of benign nerve sheath tumors include neurofibroma-schwannoma and neurofibromaperineurioma.⁴ Neurofibroma-schwannomas usually have a schwannoma component containing Antoni A areas with palisading Verocay bodies. The neurofibroma cells typically have wavy elongated nuclei, fibroblasts, and mucinous myxoid material.³ Neurofibroma-perineurioma is the least common hybrid tumor. These hybrid tumors have a plexiform neurofibroma appearance with areas of perineural differentiation, which can be difficult to identify on routine histology and typically will require IHC staining to appreciate. The neurofibroma component will stain positive for S-100 and negative for markers of perineural differentiation, including epithelial membrane antigen, glucose transporter-1, and Claudin-1.³ Although schwannoma-perineuriomas are benign sporadic tumors not associated with neurofibromatosis, neurofibromaschwannomas are associated with neurofibromatosis types 1 and 2 (NF1 and NF2). Neurofibroma-perineurioma tumors usually are associated with only NF1.^3,6

Schwannomas typically present in middle-aged patients as tumors located on flexor surfaces.⁷ Although perineural cells can be seen at the periphery of a schwannoma forming a capsule, they do not interdigitate between the Schwann cells. Schwannomas are composed almost entirely of well-differentiated Schwann cells.^1,4,8 Schwannomas classically are well-circumscribed, encapsulated, biphasic lesions with alternating compact areas (Antoni A) and loosely arranged areas (Antoni B). The spindled cells occasionally may display nuclear palisading within the Antoni A areas, known as Verocay bodies (Figure 2). Antoni B areas are more disorganized and hypocellular with variable macrophage infiltrate.^1,4,8 The Schwann cells predominantly will have bland cytologic features, but scattered areas of degenerative nuclear atypia (also known as ancient change) may be present.⁴ Multiple schwannomas are associated with NF2 gene mutations and loss of merlin protein.8 There are different subtypes of schwannomas, including cellular and plexiform schwannomas.⁴ Because schwannomas are benign nerve sheath lesions, treatment typically consists of excision with careful dissection around the involved nerve.⁹

Neurofibromas are the most common peripheral nerve sheath tumors of the skin with no notable anatomic prediction, though one study found them to be more prevalent in the upper extremities.¹⁰ They typically present as sporadic solitary lesions, but multiple lesions may appear as superficial pedunculated growths that present in those aged 20 to 30 years.¹¹ Microscopically, neurofibromas typically are not well circumscribed and have an infiltrative growth pattern. Neurofibromas are composed of cytologically bland spindled Schwann cells with thin wavy nuclei in a variable myxoid stroma (Figure 3). In addition to Schwann cells, neurofibromas contain other cell components, including fibroblasts, mast cells, perineurial-like cells, and residual axons.⁴ Neurofibromas typically are located in the dermis but may extend into the subcutaneous tissue. Clinically, the overlying skin may show hyperpigmentation.8 Neurofibromas can be localized, diffuse, or plexiform, with the majority being localized. Diffuse neurofibromas clinically have a raised plaque appearance. Treatment is unnecessary because these lesions are benign.⁷

Desmoplastic melanoma (DM) is another diagnosis in the differential for this case. Patients with DM are older compared to non-DM melanoma patients, with a male predilection.¹² Desmoplastic melanomas are more likely to be located on the head and neck. In approximately one-third of cases, no in situ component will be identified, leading to confusion of the dermal lesion as a neural lesion or an area of scar formation. Microscopically, DM presents as a variable cellular infiltrative tumor composed of spindle cells with varying degrees of nuclear atypia. The spindled melanocytes are within a collagenous (desmoplastic) stroma (Figure 4).¹³ Desmoplastic melanoma has been described with a low mitotic index, leading to misdiagnosis with benign spindle cell neoplasms.¹⁴ The spindle cells should be positive for S-100 and SOX-10 with IHC staining. Unlike other melanomas, human melanoma black 45 and Melan-A often are negative or only focally positive. Treatment of DM is similar to non-DM in that wide local excision usually is employed. A systematic review evaluating sentinel lymph node biopsy (SLNB) recommended consideration of SLNB in mixed DM but not for pure DM, as rates of positive SLNB were much lower in the latter.¹⁵

Patients with malignant peripheral nerve sheath tumor (MPNST) usually present with an enlarging mass, pain, or neurologic symptoms. Most cases of MPNST are located on the trunk or extremities.¹⁶ Plexiform neurofibromas, especially in adults with NF1, have the potential to transform into an MPNST.⁴ In fact, MPNST is the most common malignancy in patients with NF1.¹⁷ Pediatric cancer survivors also are predisposed to MPNST, with a 40-fold increase in incidence compared to the general population.¹⁸ Transformation from schwannoma to MPNST is rare but has been reported.⁸ Histologically, spindle cells easily can be appreciated with a fasciculated growth pattern (Figure 5). Mitotic activity and tumor necrosis may be present. Diagnosis of these tumors historically has been challenging, though recent research has identified inactivation of polycomb repressive complex 2 in 70% to 90% of MPNSTs. Because of polycomb repressive complex 2 inactivation, there is loss of stone H3K27 trimethylation that can be capitalized on for MPNST diagnosis.¹⁹ Negative IHC staining for H3K27 trimethylation has been found to be highly specific for MPNST. Negative staining for different cytokeratin and melanoma markers can be helpful in differentiating it from carcinomas and melanoma. The only curative treatment for MPNST is complete excision, leaving patients with recurrent, refractory, and metastatic cases to be encouraged for enrollment in clinical trials. The 5-year survival rates for patients with MPNST reported in the literature range from 20% to 50%.²⁰

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

A new type of wound dressing might change burn care for the better with one amazing property: dissolvability. Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.

“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”

Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
 

A better bandage

Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.

Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.

“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.

The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.

“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.

The solution dissolves the hydrogel in 4-6 minutes.
 

Hybrid gels

Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.

“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.

The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.

The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.

And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.

When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.

“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.

The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.

This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.

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

A new type of wound dressing might change burn care for the better with one amazing property: dissolvability. Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.

“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”

Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
 

A better bandage

Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.

Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.

“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.

The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.

“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.

The solution dissolves the hydrogel in 4-6 minutes.
 

Hybrid gels

Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.

“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.

The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.

The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.

And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.

When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.

“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.

The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.

This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.

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

A new type of wound dressing might change burn care for the better with one amazing property: dissolvability. Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.

“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”

Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
 

A better bandage

Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.

Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.

“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.

The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.

“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.

The solution dissolves the hydrogel in 4-6 minutes.
 

Hybrid gels

Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.

“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.

The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.

The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.

And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.

When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.

“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.

The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.

This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.

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

Dr Anca Askanase, director of the Lupus Center at Columbia University Medical Center, highlights the latest research on systemic lupus erythematosus (SLE) and lupus nephritis from the American College of Rheumatology (ACR) 2022.  

Dr Askanase first discusses a small study using autologous chimeric antigen receptor T-cell (CAR-T) therapy, which is approved for use in several blood cancers, as an alternative for patients with refractory SLE. Five patients received CAR-T cells, and all achieved sustained, drug-free remission. 

Next, Dr Askanase highlights a phase 2B study evaluating the tyrosine kinase 2 inhibitor deucravacitinib in patients with SLE. In early results, patients taking deucravacitinib showed a statistically meaningful response in disease activity compared with placebo.   

She then summarizes her presentation on oral cenerimod. The phase 2, 12-week study demonstrated that cenerimod reduced total lymphocyte count compared with placebo in SLE patients.  

Next, Dr Askanase details the long-term extension of the TULIP trials. Researchers found that anifrolumab has a favorable benefit-risk profile when compared with placebo and is therefore a possible long-term treatment option for patients with moderate to severe SLE.   

Finally, Dr Askanase discusses the positive findings from the phase 3 AURORA 1 and AURORA 2 studies, which sought to determine whether the addition of voclosporin to mycophenolate mofetil and low-dose steroids could maintain the reduction in proteinuria in patients with lupus nephritis. 

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Anca Askanase, MD, MPH, Professor of Medicine, Director, Lupus Center, Department of Rheumatology, Columbia University Medical Center, New York, New York 

Anca Askanase, MD, MPH, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer 

Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer 

Dr Anca Askanase, director of the Lupus Center at Columbia University Medical Center, highlights the latest research on systemic lupus erythematosus (SLE) and lupus nephritis from the American College of Rheumatology (ACR) 2022.  

Dr Askanase first discusses a small study using autologous chimeric antigen receptor T-cell (CAR-T) therapy, which is approved for use in several blood cancers, as an alternative for patients with refractory SLE. Five patients received CAR-T cells, and all achieved sustained, drug-free remission. 

Next, Dr Askanase highlights a phase 2B study evaluating the tyrosine kinase 2 inhibitor deucravacitinib in patients with SLE. In early results, patients taking deucravacitinib showed a statistically meaningful response in disease activity compared with placebo.   

She then summarizes her presentation on oral cenerimod. The phase 2, 12-week study demonstrated that cenerimod reduced total lymphocyte count compared with placebo in SLE patients.  

Next, Dr Askanase details the long-term extension of the TULIP trials. Researchers found that anifrolumab has a favorable benefit-risk profile when compared with placebo and is therefore a possible long-term treatment option for patients with moderate to severe SLE.   

Finally, Dr Askanase discusses the positive findings from the phase 3 AURORA 1 and AURORA 2 studies, which sought to determine whether the addition of voclosporin to mycophenolate mofetil and low-dose steroids could maintain the reduction in proteinuria in patients with lupus nephritis. 

--

Anca Askanase, MD, MPH, Professor of Medicine, Director, Lupus Center, Department of Rheumatology, Columbia University Medical Center, New York, New York 

Anca Askanase, MD, MPH, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer 

Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer 

Dr Anca Askanase, director of the Lupus Center at Columbia University Medical Center, highlights the latest research on systemic lupus erythematosus (SLE) and lupus nephritis from the American College of Rheumatology (ACR) 2022.  

Dr Askanase first discusses a small study using autologous chimeric antigen receptor T-cell (CAR-T) therapy, which is approved for use in several blood cancers, as an alternative for patients with refractory SLE. Five patients received CAR-T cells, and all achieved sustained, drug-free remission. 

Next, Dr Askanase highlights a phase 2B study evaluating the tyrosine kinase 2 inhibitor deucravacitinib in patients with SLE. In early results, patients taking deucravacitinib showed a statistically meaningful response in disease activity compared with placebo.   

She then summarizes her presentation on oral cenerimod. The phase 2, 12-week study demonstrated that cenerimod reduced total lymphocyte count compared with placebo in SLE patients.  

Next, Dr Askanase details the long-term extension of the TULIP trials. Researchers found that anifrolumab has a favorable benefit-risk profile when compared with placebo and is therefore a possible long-term treatment option for patients with moderate to severe SLE.   

Finally, Dr Askanase discusses the positive findings from the phase 3 AURORA 1 and AURORA 2 studies, which sought to determine whether the addition of voclosporin to mycophenolate mofetil and low-dose steroids could maintain the reduction in proteinuria in patients with lupus nephritis. 

--

Anca Askanase, MD, MPH, Professor of Medicine, Director, Lupus Center, Department of Rheumatology, Columbia University Medical Center, New York, New York 

Anca Askanase, MD, MPH, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer 

Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol Myers Squibb; Celgene; Eli Lilly; GSK; Idorsia; Janssen; Pfizer