Clinician Reviews

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

Two widely used rotavirus vaccines performed comparably in a meta-analysis, reducing risk of rotavirus gastroenteritis (RVGE) by more than 60% in young children. While the findings evidence a high protection level and low-risk safety profile, investigators of the study called for additional head-to-head comparisons to assess risks and benefits.

RVGE, which accounts for 28.8% of all deaths from diarrhea worldwide, is the leading cause of diarrhea in children under age 5. More than 100 countries include rotavirus vaccines in their immunization programs. Among six types of vaccines currently in use, two live-attenuated oral vaccines: the two-dose monovalent Rotarix (RV1) and three-dose pentavalent RotaTeq (RV5]) are in use worldwide.

Not much is known about their interchangeability, although a previous meta-analysis reported similarities in effectiveness of Rotarix (83%), RotaTeq (85%), and Rotarix and RotaTeq mixed series (86%) in low-mortality countries. RVGE morbidity and mortality have declined since the introduction of these vaccines, but concerns persist about their safety, Zi-Wei Sun, MSc, of Nanjing (China) Medical University and colleagues wrote in JAMA Pediatrics.

Their systematic review and meta-analysis of randomized clinical trials, case-control, and cohort studies compared benefit, risk, and immunogenicity of these vaccines and their effectiveness in reducing RVGE. Combing through databases Embase, PubMed, the Cochrane Library, and Web of Science using search terms “rotavirus” and “vaccine,” they chose 121 randomized clinical trials and cohort and case-control studies that included more than 100 children younger than 5 years. Thirty-eight of the randomized clinical trials had related data that examined the vaccines’ protection against RVGE hospitalization, study coauthor Hemant Goyal, MD, FACP, explained in an interview.

All of the studies reported on the safety and effectiveness or immunogenicity of rotavirus vaccines. The investigators used a random-effects model to calculate relative risks, odds ratios, risk differences, and 95% confidence intervals. They also stratified studies by economic development of countries, given that vaccine efficacy is often higher in middle- and high-income countries, compared with low-income countries. An adjusted indirect treatment comparison evaluated differences in vaccine protection among different subgroups, adopting P < .05 as the level of statistical significance.

Primary outcomes included RVGE, severe RVGE, and RVGE hospitalization and safety-associated outcomes such as serious adverse events, intussusception, and mortality.

Rotarix and RotaTeq reduced RVGE in children younger than 5 years by 68.4% and 63.6%, respectively. Dr. Goyal and colleagues confirmed these results in case-control studies (65.3% and 72.8%, respectively). Both vaccines significantly reduced RVGE and RVGE hospitalization risk and demonstrated higher protection against severe RVGE. In adjusted indirect comparisons, the two vaccines showed no significant differences in protection. They also found a positive correlation between immunogenicity and vaccine protection.

“RotaTeq seems to show lower protection in low-income countries, compared with Rotarix, but these estimates should be interpreted with caution as there was only one study for low-income countries and indirect comparison," said Dr. Goyal, a second-year gastroenterology fellow at the Wright Center for Graduate Medical Education, Scranton, Penn.

None of the vaccines demonstrated risk of serious adverse events. However, an Australian study in 2013 did report a small increased risk of intussusception after RV1 and RV5 vaccination. “Therefore, continuous surveillance of the benefits and adverse effects of rotavirus vaccines is required after vaccination,” the investigators noted.

Analyzing newer, less widely distributed vaccines, Rotavac, Rotasiil, and Lanzhou lamb rotavirus vaccine also showed moderate effectiveness in reducing RVGE risk.
 

Immunity wanes over time

Protection against rotavirus diseases seems to wane over time after vaccination. “Although our results indicated that rotavirus vaccines can provide substantial protection against RVGE during the first 2 years of life, more studies following up the vaccine efficacy for more than 2 years are required,” the investigators recommended.

Declining vaccine-induced antibodies, RVGE-acquired protection from the vaccine’s indirect effects, or exposure to unvaccinated populations may explain gradual loss of immunity.

Monitoring of rotavirus strains following vaccination should take place “to avoid population-based selection of so-called escape strains, especially fully heterotypic strains and new strains, because of the long-term pressure of vaccine immunity,” they recommended.

The findings emphasize the importance of introducing vaccines worldwide to reduce infection, summarized Dr. Goyal and colleagues. Given how challenging it is to treat the wide varieties of rotavirus, “It encouraging that RV1 and RV5 work well against heterotypic strains,” they added. Similar performance between Rotarix and RotaTeq also makes it easier for clinicians to choose a vaccine.

Increasing the availability and efficacy of these vaccines in low-income countries with high mortality rates is a high priority,

David I. Bernstein, MD, MA, wrote in a related editorial: “A clear gradient in vaccine protections was noted by country income level in the analysis presented, and much effort has been spent to understand this discrepancy.”

Overall, the study confirmed the efficacy of these two vaccines and their equivalence, noted Dr. Bernstein.

The study’s literature search process had some limitations. “Especially in stratified analyses, sparse data in some subgroups limit generalizability. ... The most accurate method, head-to-head comparisons, to evaluate the comparative efficacy of different vaccines is required in further studies,” the study investigators wrote.

Such studies would directly compare Rotarix and RotaTeq from multiple perspectives: efficacy, cost-effectiveness, strain-specific protection, the duration of protection, safety, and immunogenicity, said Dr. Goyal.

*This story was updated on May 24, 2021.

Two widely used rotavirus vaccines performed comparably in a meta-analysis, reducing risk of rotavirus gastroenteritis (RVGE) by more than 60% in young children. While the findings evidence a high protection level and low-risk safety profile, investigators of the study called for additional head-to-head comparisons to assess risks and benefits.

RVGE, which accounts for 28.8% of all deaths from diarrhea worldwide, is the leading cause of diarrhea in children under age 5. More than 100 countries include rotavirus vaccines in their immunization programs. Among six types of vaccines currently in use, two live-attenuated oral vaccines: the two-dose monovalent Rotarix (RV1) and three-dose pentavalent RotaTeq (RV5]) are in use worldwide.

Not much is known about their interchangeability, although a previous meta-analysis reported similarities in effectiveness of Rotarix (83%), RotaTeq (85%), and Rotarix and RotaTeq mixed series (86%) in low-mortality countries. RVGE morbidity and mortality have declined since the introduction of these vaccines, but concerns persist about their safety, Zi-Wei Sun, MSc, of Nanjing (China) Medical University and colleagues wrote in JAMA Pediatrics.

Their systematic review and meta-analysis of randomized clinical trials, case-control, and cohort studies compared benefit, risk, and immunogenicity of these vaccines and their effectiveness in reducing RVGE. Combing through databases Embase, PubMed, the Cochrane Library, and Web of Science using search terms “rotavirus” and “vaccine,” they chose 121 randomized clinical trials and cohort and case-control studies that included more than 100 children younger than 5 years. Thirty-eight of the randomized clinical trials had related data that examined the vaccines’ protection against RVGE hospitalization, study coauthor Hemant Goyal, MD, FACP, explained in an interview.

All of the studies reported on the safety and effectiveness or immunogenicity of rotavirus vaccines. The investigators used a random-effects model to calculate relative risks, odds ratios, risk differences, and 95% confidence intervals. They also stratified studies by economic development of countries, given that vaccine efficacy is often higher in middle- and high-income countries, compared with low-income countries. An adjusted indirect treatment comparison evaluated differences in vaccine protection among different subgroups, adopting P < .05 as the level of statistical significance.

Primary outcomes included RVGE, severe RVGE, and RVGE hospitalization and safety-associated outcomes such as serious adverse events, intussusception, and mortality.

Rotarix and RotaTeq reduced RVGE in children younger than 5 years by 68.4% and 63.6%, respectively. Dr. Goyal and colleagues confirmed these results in case-control studies (65.3% and 72.8%, respectively). Both vaccines significantly reduced RVGE and RVGE hospitalization risk and demonstrated higher protection against severe RVGE. In adjusted indirect comparisons, the two vaccines showed no significant differences in protection. They also found a positive correlation between immunogenicity and vaccine protection.

“RotaTeq seems to show lower protection in low-income countries, compared with Rotarix, but these estimates should be interpreted with caution as there was only one study for low-income countries and indirect comparison," said Dr. Goyal, a second-year gastroenterology fellow at the Wright Center for Graduate Medical Education, Scranton, Penn.

None of the vaccines demonstrated risk of serious adverse events. However, an Australian study in 2013 did report a small increased risk of intussusception after RV1 and RV5 vaccination. “Therefore, continuous surveillance of the benefits and adverse effects of rotavirus vaccines is required after vaccination,” the investigators noted.

Analyzing newer, less widely distributed vaccines, Rotavac, Rotasiil, and Lanzhou lamb rotavirus vaccine also showed moderate effectiveness in reducing RVGE risk.
 

Immunity wanes over time

Protection against rotavirus diseases seems to wane over time after vaccination. “Although our results indicated that rotavirus vaccines can provide substantial protection against RVGE during the first 2 years of life, more studies following up the vaccine efficacy for more than 2 years are required,” the investigators recommended.

Declining vaccine-induced antibodies, RVGE-acquired protection from the vaccine’s indirect effects, or exposure to unvaccinated populations may explain gradual loss of immunity.

Monitoring of rotavirus strains following vaccination should take place “to avoid population-based selection of so-called escape strains, especially fully heterotypic strains and new strains, because of the long-term pressure of vaccine immunity,” they recommended.

The findings emphasize the importance of introducing vaccines worldwide to reduce infection, summarized Dr. Goyal and colleagues. Given how challenging it is to treat the wide varieties of rotavirus, “It encouraging that RV1 and RV5 work well against heterotypic strains,” they added. Similar performance between Rotarix and RotaTeq also makes it easier for clinicians to choose a vaccine.

Increasing the availability and efficacy of these vaccines in low-income countries with high mortality rates is a high priority,

David I. Bernstein, MD, MA, wrote in a related editorial: “A clear gradient in vaccine protections was noted by country income level in the analysis presented, and much effort has been spent to understand this discrepancy.”

Overall, the study confirmed the efficacy of these two vaccines and their equivalence, noted Dr. Bernstein.

The study’s literature search process had some limitations. “Especially in stratified analyses, sparse data in some subgroups limit generalizability. ... The most accurate method, head-to-head comparisons, to evaluate the comparative efficacy of different vaccines is required in further studies,” the study investigators wrote.

Such studies would directly compare Rotarix and RotaTeq from multiple perspectives: efficacy, cost-effectiveness, strain-specific protection, the duration of protection, safety, and immunogenicity, said Dr. Goyal.

*This story was updated on May 24, 2021.

Two widely used rotavirus vaccines performed comparably in a meta-analysis, reducing risk of rotavirus gastroenteritis (RVGE) by more than 60% in young children. While the findings evidence a high protection level and low-risk safety profile, investigators of the study called for additional head-to-head comparisons to assess risks and benefits.

RVGE, which accounts for 28.8% of all deaths from diarrhea worldwide, is the leading cause of diarrhea in children under age 5. More than 100 countries include rotavirus vaccines in their immunization programs. Among six types of vaccines currently in use, two live-attenuated oral vaccines: the two-dose monovalent Rotarix (RV1) and three-dose pentavalent RotaTeq (RV5]) are in use worldwide.

Not much is known about their interchangeability, although a previous meta-analysis reported similarities in effectiveness of Rotarix (83%), RotaTeq (85%), and Rotarix and RotaTeq mixed series (86%) in low-mortality countries. RVGE morbidity and mortality have declined since the introduction of these vaccines, but concerns persist about their safety, Zi-Wei Sun, MSc, of Nanjing (China) Medical University and colleagues wrote in JAMA Pediatrics.

Their systematic review and meta-analysis of randomized clinical trials, case-control, and cohort studies compared benefit, risk, and immunogenicity of these vaccines and their effectiveness in reducing RVGE. Combing through databases Embase, PubMed, the Cochrane Library, and Web of Science using search terms “rotavirus” and “vaccine,” they chose 121 randomized clinical trials and cohort and case-control studies that included more than 100 children younger than 5 years. Thirty-eight of the randomized clinical trials had related data that examined the vaccines’ protection against RVGE hospitalization, study coauthor Hemant Goyal, MD, FACP, explained in an interview.

All of the studies reported on the safety and effectiveness or immunogenicity of rotavirus vaccines. The investigators used a random-effects model to calculate relative risks, odds ratios, risk differences, and 95% confidence intervals. They also stratified studies by economic development of countries, given that vaccine efficacy is often higher in middle- and high-income countries, compared with low-income countries. An adjusted indirect treatment comparison evaluated differences in vaccine protection among different subgroups, adopting P < .05 as the level of statistical significance.

Primary outcomes included RVGE, severe RVGE, and RVGE hospitalization and safety-associated outcomes such as serious adverse events, intussusception, and mortality.

Rotarix and RotaTeq reduced RVGE in children younger than 5 years by 68.4% and 63.6%, respectively. Dr. Goyal and colleagues confirmed these results in case-control studies (65.3% and 72.8%, respectively). Both vaccines significantly reduced RVGE and RVGE hospitalization risk and demonstrated higher protection against severe RVGE. In adjusted indirect comparisons, the two vaccines showed no significant differences in protection. They also found a positive correlation between immunogenicity and vaccine protection.

“RotaTeq seems to show lower protection in low-income countries, compared with Rotarix, but these estimates should be interpreted with caution as there was only one study for low-income countries and indirect comparison," said Dr. Goyal, a second-year gastroenterology fellow at the Wright Center for Graduate Medical Education, Scranton, Penn.

None of the vaccines demonstrated risk of serious adverse events. However, an Australian study in 2013 did report a small increased risk of intussusception after RV1 and RV5 vaccination. “Therefore, continuous surveillance of the benefits and adverse effects of rotavirus vaccines is required after vaccination,” the investigators noted.

Analyzing newer, less widely distributed vaccines, Rotavac, Rotasiil, and Lanzhou lamb rotavirus vaccine also showed moderate effectiveness in reducing RVGE risk.
 

Immunity wanes over time

Protection against rotavirus diseases seems to wane over time after vaccination. “Although our results indicated that rotavirus vaccines can provide substantial protection against RVGE during the first 2 years of life, more studies following up the vaccine efficacy for more than 2 years are required,” the investigators recommended.

Declining vaccine-induced antibodies, RVGE-acquired protection from the vaccine’s indirect effects, or exposure to unvaccinated populations may explain gradual loss of immunity.

Monitoring of rotavirus strains following vaccination should take place “to avoid population-based selection of so-called escape strains, especially fully heterotypic strains and new strains, because of the long-term pressure of vaccine immunity,” they recommended.

The findings emphasize the importance of introducing vaccines worldwide to reduce infection, summarized Dr. Goyal and colleagues. Given how challenging it is to treat the wide varieties of rotavirus, “It encouraging that RV1 and RV5 work well against heterotypic strains,” they added. Similar performance between Rotarix and RotaTeq also makes it easier for clinicians to choose a vaccine.

Increasing the availability and efficacy of these vaccines in low-income countries with high mortality rates is a high priority,

David I. Bernstein, MD, MA, wrote in a related editorial: “A clear gradient in vaccine protections was noted by country income level in the analysis presented, and much effort has been spent to understand this discrepancy.”

Overall, the study confirmed the efficacy of these two vaccines and their equivalence, noted Dr. Bernstein.

The study’s literature search process had some limitations. “Especially in stratified analyses, sparse data in some subgroups limit generalizability. ... The most accurate method, head-to-head comparisons, to evaluate the comparative efficacy of different vaccines is required in further studies,” the study investigators wrote.

Such studies would directly compare Rotarix and RotaTeq from multiple perspectives: efficacy, cost-effectiveness, strain-specific protection, the duration of protection, safety, and immunogenicity, said Dr. Goyal.

*This story was updated on May 24, 2021.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

A new online survey of inflammatory bowel disease (IBD) patients found that individuals seeking information on social media are generally satisfied with the care that they get from their health care providers. However, the online activity suggested a desire for more information, especially with respect to supportive needs like diet and complementary/alternative medicine (CAM).

SonerCdem/Thinkstock

The study was led by Idan Goren, MD, and Henit Yanai, MD, of Rabin Medical Center, Petah Tikva, Israel.

The researchers suspected that social media users with IBD were looking for information they weren’t getting from their provider, so the researchers set out to identify those specific unmet needs. In a pilot exploratory phase of their investigation, they conducted an initial survey followed by an analysis of social media posts, then they conducted a second phase with a survey based on the findings in the pilot exploration.

The initial survey was conducted within a social media platform in Israel called Camoni, where patients can interact with each other and with health care providers who have experience treating IBD, including gastroenterologists, dietitians, and psychologists. The survey included 10 items about disease characteristics, information needs, information search habits, and other factors. The subsequent analysis step included individual posts on the network between January 2014 and January 2019; the investigators categorized posts by the topics of interest brought up in the initial survey and determined the frequency of posts related to each category.

Out of the 255 respondents to this initial survey, 72% reported satisfaction with the information they received in person. In addition, 67% said that search engines like Google were their most important source of disease-related information, 58% reported relying heavily on websites, and 53% reported relying on health care providers. The most common topics of interest were diet (65%), medications and their potential adverse effects (58%), disease management (48%), and CAM (43%).

After this pilot exploratory phase, the researchers developed a structured survey that they used in IBD-based forums on Facebook and other social networks. Data were collected from this survey during a 4-week period in November 2019.

About half of the 534 respondents to the more widely distributed follow-up survey were in Israel. Overall, 83% reported using IBD-related medications, 45% of which were biologics. Out of the 534 respondents, 70% primarily received treatment from IBD referral centers. Interestingly, 77% said that they would prefer to rely on social media that is guided by health care providers, but only 22% reported that they actually used such a network. Responding along a visual analog scale, they reported general satisfaction with their routine IBD care (mean score, 79 ± 27 out of 100), their providers’ effectiveness of communication (82 ± 24), and the providers’ ability to understand patient concerns (73 ± 28). Those who were active in social media rated accessibility of IBD service as 68 ± 30. Exploration of topical interest found the most common to be diet (46%), lifestyle (45%), CAM (43%), diagnostic test interpretation (34%), and specialist referrals and reviews (31%).

The general satisfaction with information from health care providers contrasted with some previous studies that had shown that patients seeking information online often felt the opposite: For example, a 2019 Canadian survey found that only 10%-36% of IBD patients believed they received adequate information on IBD issues during clinical visits. The authors of the current study speculated that the incongruence might be explained by the fact that the current survey included patients with greater disease burden, who might get more attention during clinic visits than might patients with milder illness.

“In conclusion, our results indicate that patients’ activity on [social media] appears to be independent of their satisfaction with formal IBD care and rather reflects the contemporary need for ongoing information, particularly focused on supportive needs, such as diet and CAM,” the investigators wrote.
 

“Try not to Google everything”

The findings weren’t surprising, but the researchers found that patients seeking information online often have a high level of disease burden, as evidenced by biologics use and a majority being seen by specialists. That’s worrisome, said Jason Reich, MD, a gastroenterologist in Fall River, Mass., who has also studied social media use among IBD patients but was not involved in this study. “The last person you want getting poor-quality information is someone with pretty active disease,” said Dr. Reich in an interview.

Dr. Reich agreed with the authors that IBD specialists should consider having a dietitian in their clinic, or at least refer patients to dietitians early on. He also advocated for gastroenterologists (and all physicians, really) to have an online presence, if possible. “At least make themselves and their office accessible. I always tell my patients, if you have questions, try not to Google everything online and just shoot me a message through the portal instead,” said Dr. Reich. He added that nurses can handle such duties, especially those trained in IBD. “Personally, I don’t mind sending my short messages back and forth. Especially if it’s just a question. That’s easy enough to do when it takes maybe a minute or 2.”

The authors disclosed no funding sources. Dr. Reich has no relevant financial disclosures.
 

A new online survey of inflammatory bowel disease (IBD) patients found that individuals seeking information on social media are generally satisfied with the care that they get from their health care providers. However, the online activity suggested a desire for more information, especially with respect to supportive needs like diet and complementary/alternative medicine (CAM).

SonerCdem/Thinkstock

The study was led by Idan Goren, MD, and Henit Yanai, MD, of Rabin Medical Center, Petah Tikva, Israel.

The researchers suspected that social media users with IBD were looking for information they weren’t getting from their provider, so the researchers set out to identify those specific unmet needs. In a pilot exploratory phase of their investigation, they conducted an initial survey followed by an analysis of social media posts, then they conducted a second phase with a survey based on the findings in the pilot exploration.

The initial survey was conducted within a social media platform in Israel called Camoni, where patients can interact with each other and with health care providers who have experience treating IBD, including gastroenterologists, dietitians, and psychologists. The survey included 10 items about disease characteristics, information needs, information search habits, and other factors. The subsequent analysis step included individual posts on the network between January 2014 and January 2019; the investigators categorized posts by the topics of interest brought up in the initial survey and determined the frequency of posts related to each category.

Out of the 255 respondents to this initial survey, 72% reported satisfaction with the information they received in person. In addition, 67% said that search engines like Google were their most important source of disease-related information, 58% reported relying heavily on websites, and 53% reported relying on health care providers. The most common topics of interest were diet (65%), medications and their potential adverse effects (58%), disease management (48%), and CAM (43%).

After this pilot exploratory phase, the researchers developed a structured survey that they used in IBD-based forums on Facebook and other social networks. Data were collected from this survey during a 4-week period in November 2019.

About half of the 534 respondents to the more widely distributed follow-up survey were in Israel. Overall, 83% reported using IBD-related medications, 45% of which were biologics. Out of the 534 respondents, 70% primarily received treatment from IBD referral centers. Interestingly, 77% said that they would prefer to rely on social media that is guided by health care providers, but only 22% reported that they actually used such a network. Responding along a visual analog scale, they reported general satisfaction with their routine IBD care (mean score, 79 ± 27 out of 100), their providers’ effectiveness of communication (82 ± 24), and the providers’ ability to understand patient concerns (73 ± 28). Those who were active in social media rated accessibility of IBD service as 68 ± 30. Exploration of topical interest found the most common to be diet (46%), lifestyle (45%), CAM (43%), diagnostic test interpretation (34%), and specialist referrals and reviews (31%).

The general satisfaction with information from health care providers contrasted with some previous studies that had shown that patients seeking information online often felt the opposite: For example, a 2019 Canadian survey found that only 10%-36% of IBD patients believed they received adequate information on IBD issues during clinical visits. The authors of the current study speculated that the incongruence might be explained by the fact that the current survey included patients with greater disease burden, who might get more attention during clinic visits than might patients with milder illness.

“In conclusion, our results indicate that patients’ activity on [social media] appears to be independent of their satisfaction with formal IBD care and rather reflects the contemporary need for ongoing information, particularly focused on supportive needs, such as diet and CAM,” the investigators wrote.
 

“Try not to Google everything”

The findings weren’t surprising, but the researchers found that patients seeking information online often have a high level of disease burden, as evidenced by biologics use and a majority being seen by specialists. That’s worrisome, said Jason Reich, MD, a gastroenterologist in Fall River, Mass., who has also studied social media use among IBD patients but was not involved in this study. “The last person you want getting poor-quality information is someone with pretty active disease,” said Dr. Reich in an interview.

Dr. Reich agreed with the authors that IBD specialists should consider having a dietitian in their clinic, or at least refer patients to dietitians early on. He also advocated for gastroenterologists (and all physicians, really) to have an online presence, if possible. “At least make themselves and their office accessible. I always tell my patients, if you have questions, try not to Google everything online and just shoot me a message through the portal instead,” said Dr. Reich. He added that nurses can handle such duties, especially those trained in IBD. “Personally, I don’t mind sending my short messages back and forth. Especially if it’s just a question. That’s easy enough to do when it takes maybe a minute or 2.”

The authors disclosed no funding sources. Dr. Reich has no relevant financial disclosures.
 

A new online survey of inflammatory bowel disease (IBD) patients found that individuals seeking information on social media are generally satisfied with the care that they get from their health care providers. However, the online activity suggested a desire for more information, especially with respect to supportive needs like diet and complementary/alternative medicine (CAM).

SonerCdem/Thinkstock

The study was led by Idan Goren, MD, and Henit Yanai, MD, of Rabin Medical Center, Petah Tikva, Israel.

The researchers suspected that social media users with IBD were looking for information they weren’t getting from their provider, so the researchers set out to identify those specific unmet needs. In a pilot exploratory phase of their investigation, they conducted an initial survey followed by an analysis of social media posts, then they conducted a second phase with a survey based on the findings in the pilot exploration.

The initial survey was conducted within a social media platform in Israel called Camoni, where patients can interact with each other and with health care providers who have experience treating IBD, including gastroenterologists, dietitians, and psychologists. The survey included 10 items about disease characteristics, information needs, information search habits, and other factors. The subsequent analysis step included individual posts on the network between January 2014 and January 2019; the investigators categorized posts by the topics of interest brought up in the initial survey and determined the frequency of posts related to each category.

Out of the 255 respondents to this initial survey, 72% reported satisfaction with the information they received in person. In addition, 67% said that search engines like Google were their most important source of disease-related information, 58% reported relying heavily on websites, and 53% reported relying on health care providers. The most common topics of interest were diet (65%), medications and their potential adverse effects (58%), disease management (48%), and CAM (43%).

After this pilot exploratory phase, the researchers developed a structured survey that they used in IBD-based forums on Facebook and other social networks. Data were collected from this survey during a 4-week period in November 2019.

About half of the 534 respondents to the more widely distributed follow-up survey were in Israel. Overall, 83% reported using IBD-related medications, 45% of which were biologics. Out of the 534 respondents, 70% primarily received treatment from IBD referral centers. Interestingly, 77% said that they would prefer to rely on social media that is guided by health care providers, but only 22% reported that they actually used such a network. Responding along a visual analog scale, they reported general satisfaction with their routine IBD care (mean score, 79 ± 27 out of 100), their providers’ effectiveness of communication (82 ± 24), and the providers’ ability to understand patient concerns (73 ± 28). Those who were active in social media rated accessibility of IBD service as 68 ± 30. Exploration of topical interest found the most common to be diet (46%), lifestyle (45%), CAM (43%), diagnostic test interpretation (34%), and specialist referrals and reviews (31%).

The general satisfaction with information from health care providers contrasted with some previous studies that had shown that patients seeking information online often felt the opposite: For example, a 2019 Canadian survey found that only 10%-36% of IBD patients believed they received adequate information on IBD issues during clinical visits. The authors of the current study speculated that the incongruence might be explained by the fact that the current survey included patients with greater disease burden, who might get more attention during clinic visits than might patients with milder illness.

“In conclusion, our results indicate that patients’ activity on [social media] appears to be independent of their satisfaction with formal IBD care and rather reflects the contemporary need for ongoing information, particularly focused on supportive needs, such as diet and CAM,” the investigators wrote.
 

“Try not to Google everything”

The findings weren’t surprising, but the researchers found that patients seeking information online often have a high level of disease burden, as evidenced by biologics use and a majority being seen by specialists. That’s worrisome, said Jason Reich, MD, a gastroenterologist in Fall River, Mass., who has also studied social media use among IBD patients but was not involved in this study. “The last person you want getting poor-quality information is someone with pretty active disease,” said Dr. Reich in an interview.

Dr. Reich agreed with the authors that IBD specialists should consider having a dietitian in their clinic, or at least refer patients to dietitians early on. He also advocated for gastroenterologists (and all physicians, really) to have an online presence, if possible. “At least make themselves and their office accessible. I always tell my patients, if you have questions, try not to Google everything online and just shoot me a message through the portal instead,” said Dr. Reich. He added that nurses can handle such duties, especially those trained in IBD. “Personally, I don’t mind sending my short messages back and forth. Especially if it’s just a question. That’s easy enough to do when it takes maybe a minute or 2.”

The authors disclosed no funding sources. Dr. Reich has no relevant financial disclosures.
 

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

A 31-year-old Hispanic man presented for evaluation of numerous disfiguring growths on his scalp. They first appeared when he was 19 years old. A review of his family history revealed that his father had 2 “cysts” on his body.

The patient had 10 nodules on his scalp and upper back (Figures 1A and 1B). The ones on his scalp lacked puncta and appeared in a “turban tumor” configuration. The lesions were pink, smooth, and semisoft, and ranged in size from 1 to 6 cm.

Six years earlier, the patient had been seen for evaluation of 20 protuberant nodules. At the time, he had been referred to plastic surgery, where 15 lesions were excised. No other treatment was reported by the patient during the 6-year gap between exams.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Pilar cysts (PC), also known as trichilemma cysts, wen, or isthmus-catagen cysts, are benign cysts that manifest as smooth, firm, well-­circumscribed, pink nodules. PCs originate from the follicular isthmus of the hair’s external root sheath¹ and are found in 5% to 10% of the US population.² Possible sites of appearance include the face, neck, trunk, and extremities, although 90% of PCs develop on the scalp.¹ They tend to have an autosomal dominant pattern of inheritance with linkages to the short arm of chromosome 3.³ PCs can occasionally become inflamed following infection or trauma.

Characteristic histology of PCs demonstrates semisolid, keratin-filled, subepidermal cysts lined by stratified epithelium without a granular layer (trichilemmal keratinization). Lesions excised from this patient’s scalp showed 2 subtypes of PCs: nonproliferating (FIGURE 2A) and proliferating (FIGURE 2B). Subtypes appear similar on exam but can be differentiated on histology.

With gradual growth, proliferating PCs can reach up to 25 cm in diameter.¹ Rapid growth, size > 5 cm, infiltration, or a non-scalp location may indicate malignancy.⁴

Differential diagnosis includes lipomas

The differential diagnosis for a lesion such as this includes epidermal inclusion cysts, dermoid cysts, and lipomas. Epidermal inclusion cysts have a punctum, whereas PCs do not. Dermoid cysts are single congenital lesions that manifest much earlier than PCs. Lipomas are easily movable rubbery bulges that appear more frequently in lipid-dense areas of the body.

For this patient, the striking turban ­tumor–like presentation, with numerous large cysts on the scalp, initially inspired a differential diagnosis including several genetic tumor syndromes. However, unlike the association between Gardner syndrome and numerous epidermoid cysts or Brooke-Spiegler syndrome and spiradenomas, no syndromes have been linked to numerous trichilemmal cysts.

Continue to: Excision is effective

Excision is the treatment of choice for both proliferating and nonproliferating PCs.⁵ The local recurrence rate of proliferating PCs is 3.7% with a rare likelihood of transformation to trichilemmal carcinoma.⁶

Our patient continues to be followed in clinic for monitoring and periodic excision of bothersome cysts.

A 31-year-old Hispanic man presented for evaluation of numerous disfiguring growths on his scalp. They first appeared when he was 19 years old. A review of his family history revealed that his father had 2 “cysts” on his body.

The patient had 10 nodules on his scalp and upper back (Figures 1A and 1B). The ones on his scalp lacked puncta and appeared in a “turban tumor” configuration. The lesions were pink, smooth, and semisoft, and ranged in size from 1 to 6 cm.

Six years earlier, the patient had been seen for evaluation of 20 protuberant nodules. At the time, he had been referred to plastic surgery, where 15 lesions were excised. No other treatment was reported by the patient during the 6-year gap between exams.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Pilar cysts (PC), also known as trichilemma cysts, wen, or isthmus-catagen cysts, are benign cysts that manifest as smooth, firm, well-­circumscribed, pink nodules. PCs originate from the follicular isthmus of the hair’s external root sheath¹ and are found in 5% to 10% of the US population.² Possible sites of appearance include the face, neck, trunk, and extremities, although 90% of PCs develop on the scalp.¹ They tend to have an autosomal dominant pattern of inheritance with linkages to the short arm of chromosome 3.³ PCs can occasionally become inflamed following infection or trauma.

Characteristic histology of PCs demonstrates semisolid, keratin-filled, subepidermal cysts lined by stratified epithelium without a granular layer (trichilemmal keratinization). Lesions excised from this patient’s scalp showed 2 subtypes of PCs: nonproliferating (FIGURE 2A) and proliferating (FIGURE 2B). Subtypes appear similar on exam but can be differentiated on histology.

With gradual growth, proliferating PCs can reach up to 25 cm in diameter.¹ Rapid growth, size > 5 cm, infiltration, or a non-scalp location may indicate malignancy.⁴

Differential diagnosis includes lipomas

The differential diagnosis for a lesion such as this includes epidermal inclusion cysts, dermoid cysts, and lipomas. Epidermal inclusion cysts have a punctum, whereas PCs do not. Dermoid cysts are single congenital lesions that manifest much earlier than PCs. Lipomas are easily movable rubbery bulges that appear more frequently in lipid-dense areas of the body.

For this patient, the striking turban ­tumor–like presentation, with numerous large cysts on the scalp, initially inspired a differential diagnosis including several genetic tumor syndromes. However, unlike the association between Gardner syndrome and numerous epidermoid cysts or Brooke-Spiegler syndrome and spiradenomas, no syndromes have been linked to numerous trichilemmal cysts.

Continue to: Excision is effective

Excision is the treatment of choice for both proliferating and nonproliferating PCs.⁵ The local recurrence rate of proliferating PCs is 3.7% with a rare likelihood of transformation to trichilemmal carcinoma.⁶

Our patient continues to be followed in clinic for monitoring and periodic excision of bothersome cysts.

A 31-year-old Hispanic man presented for evaluation of numerous disfiguring growths on his scalp. They first appeared when he was 19 years old. A review of his family history revealed that his father had 2 “cysts” on his body.

The patient had 10 nodules on his scalp and upper back (Figures 1A and 1B). The ones on his scalp lacked puncta and appeared in a “turban tumor” configuration. The lesions were pink, smooth, and semisoft, and ranged in size from 1 to 6 cm.

Six years earlier, the patient had been seen for evaluation of 20 protuberant nodules. At the time, he had been referred to plastic surgery, where 15 lesions were excised. No other treatment was reported by the patient during the 6-year gap between exams.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Pilar cysts (PC), also known as trichilemma cysts, wen, or isthmus-catagen cysts, are benign cysts that manifest as smooth, firm, well-­circumscribed, pink nodules. PCs originate from the follicular isthmus of the hair’s external root sheath¹ and are found in 5% to 10% of the US population.² Possible sites of appearance include the face, neck, trunk, and extremities, although 90% of PCs develop on the scalp.¹ They tend to have an autosomal dominant pattern of inheritance with linkages to the short arm of chromosome 3.³ PCs can occasionally become inflamed following infection or trauma.

Characteristic histology of PCs demonstrates semisolid, keratin-filled, subepidermal cysts lined by stratified epithelium without a granular layer (trichilemmal keratinization). Lesions excised from this patient’s scalp showed 2 subtypes of PCs: nonproliferating (FIGURE 2A) and proliferating (FIGURE 2B). Subtypes appear similar on exam but can be differentiated on histology.

With gradual growth, proliferating PCs can reach up to 25 cm in diameter.¹ Rapid growth, size > 5 cm, infiltration, or a non-scalp location may indicate malignancy.⁴

Differential diagnosis includes lipomas

The differential diagnosis for a lesion such as this includes epidermal inclusion cysts, dermoid cysts, and lipomas. Epidermal inclusion cysts have a punctum, whereas PCs do not. Dermoid cysts are single congenital lesions that manifest much earlier than PCs. Lipomas are easily movable rubbery bulges that appear more frequently in lipid-dense areas of the body.

For this patient, the striking turban ­tumor–like presentation, with numerous large cysts on the scalp, initially inspired a differential diagnosis including several genetic tumor syndromes. However, unlike the association between Gardner syndrome and numerous epidermoid cysts or Brooke-Spiegler syndrome and spiradenomas, no syndromes have been linked to numerous trichilemmal cysts.

Continue to: Excision is effective

Excision is the treatment of choice for both proliferating and nonproliferating PCs.⁵ The local recurrence rate of proliferating PCs is 3.7% with a rare likelihood of transformation to trichilemmal carcinoma.⁶

Our patient continues to be followed in clinic for monitoring and periodic excision of bothersome cysts.

State health officials have shared plans to distribute Pfizer’s COVID-19 vaccine to 12- to 15-year-olds after the Food and Drug Administration authorized its use in this age group May 10.

Some states hope to start the vaccinations as early as May 13, officials said at an Association of State and Territorial Health Officials news conference.

There are, however, two more steps before shots can reach younger arms. On May 12, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is expected to recommend use of the vaccine in this age group. Then CDC Director Rochelle Walensky, MD, must make a final decision to begin vaccinating 12- to 15-year-olds.

Some hoping to start this week

Both the CDC panel and Dr. Walensky are expected to sign off on the vaccine’s use. States have been making plans on how to tailor the vaccination message not just to the patient this time, but to parents and guardians as well, some of whom are hesitant to consent.

Some schools, assuming approval May 12, are ready to start vaccinating in cafeterias and gyms.

Anne Zink, MD, president-elect of the Association of State and Territorial Health Officials and Alaska chief medical officer, told reporters that many of her state’s boroughs and districts have booked in-person vaccines for their schools May 12 as the state has dismissal for summer as early as this week.

Maine is readying four types of distribution sites for the vaccines: primary care offices, Walgreen’s and CVS pharmacies, mass vaccination sites, and schools, said Nirav Shah, MD, current ASTHO president and director of the Maine Center for Disease Control and Prevention.

Starting later this week, he said, the state hopes to host large vaccination clinics for people age 12 and over.

Eliminating barriers

States are working to break down barriers through education and improving access.

In Alaska, many of the drive-through evening vaccination sites are being changed to Pfizer sites so parents just getting off work can take their kids.

It’s also important to get young people to speak to their peers about the importance of vaccines, she said. Some teen groups in Alaska are hosting Zoom calls where they share with children and families why they chose to get vaccinated.

In Maine, Dr. Shah said, “the notion of informed consent applies with equal force to adults as it does with adolescents.” But at least in Maine, it is not required that a parent be on site and present during the vaccination itself.

A parent could sign a form allowing the child to be vaccinated in a school-based clinic. Maine also allows verbal consent so a parent can give consent over the phone, Dr. Shah said.

Dividing vaccine trays

Vaccines going to pediatrician and family medicine offices presents a challenge in that smaller numbers of doses are needed for those venues than at large vaccination sites that get trays of 1,170 Pfizer doses each.

Dr. Shah says states have been talking with federal authorities on the need for smaller packaging.

“Breaking the trays up into smaller lot sizes takes a fair amount of effort,” Dr. Shah said. “We understand that later this month the lot size will be going down to 450.”

But even that will be too much for small offices, he said.

Similarly, an effort is being made in Maine to make sure doctors’ offices are not limited by their refrigeration capabilities. The Pfizer vaccine must be kept at ultra-cold temperatures that many primary care doctors’ offices may not have.

“If they need a cool cube with dry ice, we can furnish that to them,” Dr. Shah said.

Should they be mandated?

Dr. Zink said Alaska generally has high acceptance for recommendations around COVID-19 and has no plans to mandate the COVID-19 vaccines for children.

Umair A. Shah, MD, secretary of health at the Washington State Department of Health, said, “Our number one ability to get people vaccinated is for them to be encouraged to do so, to be incentivized to do so, to do everything we can to make the vaccine choice the easy choice,” including eliminating language, cultural and access barriers.

However, he said, “in higher education, University of Washington and Washington State University have indicated they are going to require COVID vaccines for kids to come back to school. I do think that is something that is increasingly being looked at.”

Though the messages will be tailored differently across the states the bottom line will be the same, Dr. Shah said: The vaccines work and they are safe.

But most critically, “Vaccines are our pathway to moving forward and once and for all ending this pandemic,” he said.

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

State health officials have shared plans to distribute Pfizer’s COVID-19 vaccine to 12- to 15-year-olds after the Food and Drug Administration authorized its use in this age group May 10.

Some states hope to start the vaccinations as early as May 13, officials said at an Association of State and Territorial Health Officials news conference.

There are, however, two more steps before shots can reach younger arms. On May 12, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is expected to recommend use of the vaccine in this age group. Then CDC Director Rochelle Walensky, MD, must make a final decision to begin vaccinating 12- to 15-year-olds.

Some hoping to start this week

Both the CDC panel and Dr. Walensky are expected to sign off on the vaccine’s use. States have been making plans on how to tailor the vaccination message not just to the patient this time, but to parents and guardians as well, some of whom are hesitant to consent.

Some schools, assuming approval May 12, are ready to start vaccinating in cafeterias and gyms.

Anne Zink, MD, president-elect of the Association of State and Territorial Health Officials and Alaska chief medical officer, told reporters that many of her state’s boroughs and districts have booked in-person vaccines for their schools May 12 as the state has dismissal for summer as early as this week.

Maine is readying four types of distribution sites for the vaccines: primary care offices, Walgreen’s and CVS pharmacies, mass vaccination sites, and schools, said Nirav Shah, MD, current ASTHO president and director of the Maine Center for Disease Control and Prevention.

Starting later this week, he said, the state hopes to host large vaccination clinics for people age 12 and over.

Eliminating barriers

States are working to break down barriers through education and improving access.

In Alaska, many of the drive-through evening vaccination sites are being changed to Pfizer sites so parents just getting off work can take their kids.

It’s also important to get young people to speak to their peers about the importance of vaccines, she said. Some teen groups in Alaska are hosting Zoom calls where they share with children and families why they chose to get vaccinated.

In Maine, Dr. Shah said, “the notion of informed consent applies with equal force to adults as it does with adolescents.” But at least in Maine, it is not required that a parent be on site and present during the vaccination itself.

A parent could sign a form allowing the child to be vaccinated in a school-based clinic. Maine also allows verbal consent so a parent can give consent over the phone, Dr. Shah said.

Dividing vaccine trays

Vaccines going to pediatrician and family medicine offices presents a challenge in that smaller numbers of doses are needed for those venues than at large vaccination sites that get trays of 1,170 Pfizer doses each.

Dr. Shah says states have been talking with federal authorities on the need for smaller packaging.

“Breaking the trays up into smaller lot sizes takes a fair amount of effort,” Dr. Shah said. “We understand that later this month the lot size will be going down to 450.”

But even that will be too much for small offices, he said.

Similarly, an effort is being made in Maine to make sure doctors’ offices are not limited by their refrigeration capabilities. The Pfizer vaccine must be kept at ultra-cold temperatures that many primary care doctors’ offices may not have.

“If they need a cool cube with dry ice, we can furnish that to them,” Dr. Shah said.

Should they be mandated?

Dr. Zink said Alaska generally has high acceptance for recommendations around COVID-19 and has no plans to mandate the COVID-19 vaccines for children.

Umair A. Shah, MD, secretary of health at the Washington State Department of Health, said, “Our number one ability to get people vaccinated is for them to be encouraged to do so, to be incentivized to do so, to do everything we can to make the vaccine choice the easy choice,” including eliminating language, cultural and access barriers.

However, he said, “in higher education, University of Washington and Washington State University have indicated they are going to require COVID vaccines for kids to come back to school. I do think that is something that is increasingly being looked at.”

Though the messages will be tailored differently across the states the bottom line will be the same, Dr. Shah said: The vaccines work and they are safe.

But most critically, “Vaccines are our pathway to moving forward and once and for all ending this pandemic,” he said.

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

State health officials have shared plans to distribute Pfizer’s COVID-19 vaccine to 12- to 15-year-olds after the Food and Drug Administration authorized its use in this age group May 10.

Some states hope to start the vaccinations as early as May 13, officials said at an Association of State and Territorial Health Officials news conference.

There are, however, two more steps before shots can reach younger arms. On May 12, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is expected to recommend use of the vaccine in this age group. Then CDC Director Rochelle Walensky, MD, must make a final decision to begin vaccinating 12- to 15-year-olds.

Some hoping to start this week

Both the CDC panel and Dr. Walensky are expected to sign off on the vaccine’s use. States have been making plans on how to tailor the vaccination message not just to the patient this time, but to parents and guardians as well, some of whom are hesitant to consent.

Some schools, assuming approval May 12, are ready to start vaccinating in cafeterias and gyms.

Anne Zink, MD, president-elect of the Association of State and Territorial Health Officials and Alaska chief medical officer, told reporters that many of her state’s boroughs and districts have booked in-person vaccines for their schools May 12 as the state has dismissal for summer as early as this week.

Maine is readying four types of distribution sites for the vaccines: primary care offices, Walgreen’s and CVS pharmacies, mass vaccination sites, and schools, said Nirav Shah, MD, current ASTHO president and director of the Maine Center for Disease Control and Prevention.

Starting later this week, he said, the state hopes to host large vaccination clinics for people age 12 and over.

Eliminating barriers

States are working to break down barriers through education and improving access.

In Alaska, many of the drive-through evening vaccination sites are being changed to Pfizer sites so parents just getting off work can take their kids.

It’s also important to get young people to speak to their peers about the importance of vaccines, she said. Some teen groups in Alaska are hosting Zoom calls where they share with children and families why they chose to get vaccinated.

In Maine, Dr. Shah said, “the notion of informed consent applies with equal force to adults as it does with adolescents.” But at least in Maine, it is not required that a parent be on site and present during the vaccination itself.

A parent could sign a form allowing the child to be vaccinated in a school-based clinic. Maine also allows verbal consent so a parent can give consent over the phone, Dr. Shah said.

Dividing vaccine trays

Vaccines going to pediatrician and family medicine offices presents a challenge in that smaller numbers of doses are needed for those venues than at large vaccination sites that get trays of 1,170 Pfizer doses each.

Dr. Shah says states have been talking with federal authorities on the need for smaller packaging.

“Breaking the trays up into smaller lot sizes takes a fair amount of effort,” Dr. Shah said. “We understand that later this month the lot size will be going down to 450.”

But even that will be too much for small offices, he said.

Similarly, an effort is being made in Maine to make sure doctors’ offices are not limited by their refrigeration capabilities. The Pfizer vaccine must be kept at ultra-cold temperatures that many primary care doctors’ offices may not have.

“If they need a cool cube with dry ice, we can furnish that to them,” Dr. Shah said.

Should they be mandated?

Dr. Zink said Alaska generally has high acceptance for recommendations around COVID-19 and has no plans to mandate the COVID-19 vaccines for children.

Umair A. Shah, MD, secretary of health at the Washington State Department of Health, said, “Our number one ability to get people vaccinated is for them to be encouraged to do so, to be incentivized to do so, to do everything we can to make the vaccine choice the easy choice,” including eliminating language, cultural and access barriers.

However, he said, “in higher education, University of Washington and Washington State University have indicated they are going to require COVID vaccines for kids to come back to school. I do think that is something that is increasingly being looked at.”

Though the messages will be tailored differently across the states the bottom line will be the same, Dr. Shah said: The vaccines work and they are safe.

But most critically, “Vaccines are our pathway to moving forward and once and for all ending this pandemic,” he said.

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

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

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

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

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

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

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