Editor’s Picks

Richard S. Irwin, MD, Master FCCP



Giants in Chest Medicine

David C. Zavala, MD, FCCP



Original Research

Accuracy of Algorithms to Identify Pulmonary Arterial Hypertension in Administrative Data:

A Systematic Review. By K. R. Gillmeyer, et al.

Editor’s Picks

Richard S. Irwin, MD, Master FCCP



Giants in Chest Medicine

David C. Zavala, MD, FCCP



Original Research

Accuracy of Algorithms to Identify Pulmonary Arterial Hypertension in Administrative Data:

A Systematic Review. By K. R. Gillmeyer, et al.

Editor’s Picks

Richard S. Irwin, MD, Master FCCP



Giants in Chest Medicine

David C. Zavala, MD, FCCP



Original Research

Accuracy of Algorithms to Identify Pulmonary Arterial Hypertension in Administrative Data:

A Systematic Review. By K. R. Gillmeyer, et al.

In late January, your Board of Regents met for its first face-to-face quarterly meeting under the leadership of new President Clayton Cowl, MD, MS, FCCP. One of the most valuable aspects of serving on the Board is an opportunity to take an overall look at the direction of the organization. The Board makes a concerted effort not to get too deep into the weeds planning out specific tactics for achieving goals; we have a great many outstanding volunteers serving on dozens of our committees who do an incredible job of making things happen. The Board tries to focus on overall organizational strategy. Are we going in the right direction? Are there opportunities of which we should be taking better advantage? Are there efforts in which we are currently engaged that may not be yielding outcomes as we expected? To better answer these questions, Dr. Cowl and his team asked all members of the Board of Regents and the Strategic Planning Subcommittee members of the Foundation Board of Trustees, as well as senior CHEST staff, to engage in an environmental scan to take an aggressive look at where we are and where we are headed. The output from our first environmental scan is currently being curated into a list of highest priority items that will be shared with the general membership in the coming months.

A review of our accomplishments over the last 6 months came next. Our new Executive Vice President and Chief Operating Officer, Dr. Robert Musacchio, has superseded all expectations in his first few months in the role. In addition to continuing to push the organization toward the “One CHEST” model by better integrating the Foundation with the College, as well as refining our operating principles in working with industry, Bob is further developing our international reach—exploring collaborations with a number of large international societies and planning meetings abroad later this year (CHEST Congress Thailand and CHEST Regional Congress Athens) and into the next (in Italy, with the regional meeting location to be determined). We are also in the process of recruiting for a new position, Chief Learning Officer, a role that will serve not only to better organize the educational activities of CHEST, but to also serve as a visionary to better imagine what future projects we should be pursuing to be of better service and value to our members.

We took a few moments to recognize the new, incoming Editor in Chief of the journal CHEST®; Peter Mazzone, MD, FCCP, will have some huge shoes to fill in taking the editor’s chair from Richard Irwin, MD, Master FCCP, who has served the journal in this role for more than a decade. Under Dr. Irwin’s leadership, CHEST has been the most-read publication amongst practicing pulmonary specialists; he is also responsible for having launched CHEST’s social media presence, including both video series that integrated directly with the journal (such as Ultrasound Corner) and podcasts. Richard also spoke beautifully about his passion for patient-centered care as a keynote speaker at CHEST 2018. Peter has outlined a number of different areas of focus for the journal in the next year, including putting a high priority on improving the reader experience and crafting an even better web and multimedia presence. We look forward to great things from the journal!

Chris Carroll, MD, FCCP, who chairs CHEST’s Digital Strategy Task Force, presented to the Board on their progress to date. The goal of this group is to evaluate the user experience for CHEST’s content delivery platforms, including the website, apps, and our social media platforms to identify opportunities for improvements that will enable us to better provide our members with on demand, high quality information to improve patient care through a personalized, seamless digital user experience. The team is being co-led by Nicki Augustyn, Senior Vice President for Marketing, Communications, and Publishing, and Ron Moen, Chief Information Officer. We look forward to further updates on this important project.

As I stated in my opening, many of the good things that CHEST does can only happen with the participation of our great members, and so I want to take the time to recognize the NetWorks and everything that they do for the College. In the past year, under the leadership of Council of NetWorks Chairs Hassan Bencheqroun, MD, FCCP, and David Zielinski, MD, FCCP, the NetWorks produced more than 60% of the content at the 2018 CHEST meeting and are actively working on projects ranging from creating educational videos for public consumption to CHEST guidelines proposals and crafting a donor registry for lung transplantation. Our volunteer leaders are our most valuable resource; if you are not currently engaged in the NetWorks, please consider getting involved this spring during the nomination process!

It remains a privilege for the Board to serve this great organization. If you are interested in hearing more, or getting more engaged, please send me an email at [email protected].

David A. Schulman, MD, FCCP

In late January, your Board of Regents met for its first face-to-face quarterly meeting under the leadership of new President Clayton Cowl, MD, MS, FCCP. One of the most valuable aspects of serving on the Board is an opportunity to take an overall look at the direction of the organization. The Board makes a concerted effort not to get too deep into the weeds planning out specific tactics for achieving goals; we have a great many outstanding volunteers serving on dozens of our committees who do an incredible job of making things happen. The Board tries to focus on overall organizational strategy. Are we going in the right direction? Are there opportunities of which we should be taking better advantage? Are there efforts in which we are currently engaged that may not be yielding outcomes as we expected? To better answer these questions, Dr. Cowl and his team asked all members of the Board of Regents and the Strategic Planning Subcommittee members of the Foundation Board of Trustees, as well as senior CHEST staff, to engage in an environmental scan to take an aggressive look at where we are and where we are headed. The output from our first environmental scan is currently being curated into a list of highest priority items that will be shared with the general membership in the coming months.

A review of our accomplishments over the last 6 months came next. Our new Executive Vice President and Chief Operating Officer, Dr. Robert Musacchio, has superseded all expectations in his first few months in the role. In addition to continuing to push the organization toward the “One CHEST” model by better integrating the Foundation with the College, as well as refining our operating principles in working with industry, Bob is further developing our international reach—exploring collaborations with a number of large international societies and planning meetings abroad later this year (CHEST Congress Thailand and CHEST Regional Congress Athens) and into the next (in Italy, with the regional meeting location to be determined). We are also in the process of recruiting for a new position, Chief Learning Officer, a role that will serve not only to better organize the educational activities of CHEST, but to also serve as a visionary to better imagine what future projects we should be pursuing to be of better service and value to our members.

We took a few moments to recognize the new, incoming Editor in Chief of the journal CHEST®; Peter Mazzone, MD, FCCP, will have some huge shoes to fill in taking the editor’s chair from Richard Irwin, MD, Master FCCP, who has served the journal in this role for more than a decade. Under Dr. Irwin’s leadership, CHEST has been the most-read publication amongst practicing pulmonary specialists; he is also responsible for having launched CHEST’s social media presence, including both video series that integrated directly with the journal (such as Ultrasound Corner) and podcasts. Richard also spoke beautifully about his passion for patient-centered care as a keynote speaker at CHEST 2018. Peter has outlined a number of different areas of focus for the journal in the next year, including putting a high priority on improving the reader experience and crafting an even better web and multimedia presence. We look forward to great things from the journal!

Chris Carroll, MD, FCCP, who chairs CHEST’s Digital Strategy Task Force, presented to the Board on their progress to date. The goal of this group is to evaluate the user experience for CHEST’s content delivery platforms, including the website, apps, and our social media platforms to identify opportunities for improvements that will enable us to better provide our members with on demand, high quality information to improve patient care through a personalized, seamless digital user experience. The team is being co-led by Nicki Augustyn, Senior Vice President for Marketing, Communications, and Publishing, and Ron Moen, Chief Information Officer. We look forward to further updates on this important project.

As I stated in my opening, many of the good things that CHEST does can only happen with the participation of our great members, and so I want to take the time to recognize the NetWorks and everything that they do for the College. In the past year, under the leadership of Council of NetWorks Chairs Hassan Bencheqroun, MD, FCCP, and David Zielinski, MD, FCCP, the NetWorks produced more than 60% of the content at the 2018 CHEST meeting and are actively working on projects ranging from creating educational videos for public consumption to CHEST guidelines proposals and crafting a donor registry for lung transplantation. Our volunteer leaders are our most valuable resource; if you are not currently engaged in the NetWorks, please consider getting involved this spring during the nomination process!

It remains a privilege for the Board to serve this great organization. If you are interested in hearing more, or getting more engaged, please send me an email at [email protected].

David A. Schulman, MD, FCCP

In late January, your Board of Regents met for its first face-to-face quarterly meeting under the leadership of new President Clayton Cowl, MD, MS, FCCP. One of the most valuable aspects of serving on the Board is an opportunity to take an overall look at the direction of the organization. The Board makes a concerted effort not to get too deep into the weeds planning out specific tactics for achieving goals; we have a great many outstanding volunteers serving on dozens of our committees who do an incredible job of making things happen. The Board tries to focus on overall organizational strategy. Are we going in the right direction? Are there opportunities of which we should be taking better advantage? Are there efforts in which we are currently engaged that may not be yielding outcomes as we expected? To better answer these questions, Dr. Cowl and his team asked all members of the Board of Regents and the Strategic Planning Subcommittee members of the Foundation Board of Trustees, as well as senior CHEST staff, to engage in an environmental scan to take an aggressive look at where we are and where we are headed. The output from our first environmental scan is currently being curated into a list of highest priority items that will be shared with the general membership in the coming months.

A review of our accomplishments over the last 6 months came next. Our new Executive Vice President and Chief Operating Officer, Dr. Robert Musacchio, has superseded all expectations in his first few months in the role. In addition to continuing to push the organization toward the “One CHEST” model by better integrating the Foundation with the College, as well as refining our operating principles in working with industry, Bob is further developing our international reach—exploring collaborations with a number of large international societies and planning meetings abroad later this year (CHEST Congress Thailand and CHEST Regional Congress Athens) and into the next (in Italy, with the regional meeting location to be determined). We are also in the process of recruiting for a new position, Chief Learning Officer, a role that will serve not only to better organize the educational activities of CHEST, but to also serve as a visionary to better imagine what future projects we should be pursuing to be of better service and value to our members.

We took a few moments to recognize the new, incoming Editor in Chief of the journal CHEST®; Peter Mazzone, MD, FCCP, will have some huge shoes to fill in taking the editor’s chair from Richard Irwin, MD, Master FCCP, who has served the journal in this role for more than a decade. Under Dr. Irwin’s leadership, CHEST has been the most-read publication amongst practicing pulmonary specialists; he is also responsible for having launched CHEST’s social media presence, including both video series that integrated directly with the journal (such as Ultrasound Corner) and podcasts. Richard also spoke beautifully about his passion for patient-centered care as a keynote speaker at CHEST 2018. Peter has outlined a number of different areas of focus for the journal in the next year, including putting a high priority on improving the reader experience and crafting an even better web and multimedia presence. We look forward to great things from the journal!

Chris Carroll, MD, FCCP, who chairs CHEST’s Digital Strategy Task Force, presented to the Board on their progress to date. The goal of this group is to evaluate the user experience for CHEST’s content delivery platforms, including the website, apps, and our social media platforms to identify opportunities for improvements that will enable us to better provide our members with on demand, high quality information to improve patient care through a personalized, seamless digital user experience. The team is being co-led by Nicki Augustyn, Senior Vice President for Marketing, Communications, and Publishing, and Ron Moen, Chief Information Officer. We look forward to further updates on this important project.

As I stated in my opening, many of the good things that CHEST does can only happen with the participation of our great members, and so I want to take the time to recognize the NetWorks and everything that they do for the College. In the past year, under the leadership of Council of NetWorks Chairs Hassan Bencheqroun, MD, FCCP, and David Zielinski, MD, FCCP, the NetWorks produced more than 60% of the content at the 2018 CHEST meeting and are actively working on projects ranging from creating educational videos for public consumption to CHEST guidelines proposals and crafting a donor registry for lung transplantation. Our volunteer leaders are our most valuable resource; if you are not currently engaged in the NetWorks, please consider getting involved this spring during the nomination process!

It remains a privilege for the Board to serve this great organization. If you are interested in hearing more, or getting more engaged, please send me an email at [email protected].

David A. Schulman, MD, FCCP

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

[email protected]

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

[email protected]

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

[email protected]

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

Patients with celiac disease often do not receive a biopsy or nutritional recommendations at diagnosis, according to the findings of a large survey study.

Strikingly, 21% of respondents did not have a confirmatory duodenal biopsy, reported Andrew M. Joelson, MD, of Columbia University Medical Center, New York, and his associates. Gastroenterologists diagnosed 66% of biopsied patients but only 31% of nonbiopsied patients (P less than .001). “Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation,” the researchers wrote in the May issue of Clinical Gastroenterology and Hepatology.

Classic small-bowel findings in celiac disease (intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy) are not pathognomonic, making serology important for diagnosis. European guidelines discuss forgoing biopsy in children whose antitissue transglutaminase antibody titers are at least 10-fold above the upper limit of normal. However, the American College of Gastroenterology and the American Gastroenterological Association continue to recommend combining serology with confirmatory small bowel biopsy. The extent to which physicians follow this advice is unclear, the researchers noted.

Therefore, they analyzed data from a questionnaire posted on the Celiac Disease Foundation website during a 7-month period in 2016. Among 982 adults with self-reported celiac disease, 780 said their diagnosis included both serology and biopsy and 202 said they received serology only. Only 40% of these nonbiopsied respondents said they sought nutritional counseling at diagnosis, compared with 59% of biopsied patients (P less than .001). Patients diagnosed by serology alone also were more likely to report using dietary supplements to aid gluten digestion (20% vs. 9% of biopsied respondents; P less than .001).

These associations remained statistically significant after adjustment for age and sex, said the researchers. Nonbiopsied patients had a significantly lower odds of having been diagnosed by a gastroenterologist (odds ratio, 0.16; 95% confidence interval, 0.07-0.37) and seeking nutritional counseling (OR, 0.45; 95% CI, 0.33-0.63) and were significantly more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19).

Fully 87% of respondents always followed a strict gluten-free diet, but symptoms persisted in 65% of those who were not biopsied, compared with only 51% of those who were biopsied. There were too few responses to this question for the difference between groups to reach statistical significance, but the finding might reflect the greater diagnostic accuracy of biopsy, the researchers said. However, they cautioned that none of the associations in this study were necessarily causal, diagnoses were not independently validated, and the reliability of self-reported celiac diagnosis remains unclear.

Survey respondents also were self-selected – for example, 91% self-identified as white and 60% reported having a bachelor’s degree, compared with only about 77% and one-third of adults captured by U.S. Census Bureau data from 2017.

“Although these characteristics may limit the generalizability of our findings, this study nevertheless reflects a population of celiac disease that is not typically studied, such as those not attending large academic celiac disease centers, and those diagnosed without the involvement of a gastroenterologist,” the researchers wrote. “Future studies are warranted to further characterize this population regarding the long-term consequences of forgoing the duodenal biopsy, and to develop educational interventions to promote evidence-based diagnosis and management of celiac disease.”

SOURCE: Joelson AM et al. Clin Gastroenterol Hepatol. 2018 Sep 10. doi: 10.1016/j.cgh.2018.09.006.

Patients with celiac disease often do not receive a biopsy or nutritional recommendations at diagnosis, according to the findings of a large survey study.

Strikingly, 21% of respondents did not have a confirmatory duodenal biopsy, reported Andrew M. Joelson, MD, of Columbia University Medical Center, New York, and his associates. Gastroenterologists diagnosed 66% of biopsied patients but only 31% of nonbiopsied patients (P less than .001). “Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation,” the researchers wrote in the May issue of Clinical Gastroenterology and Hepatology.

Classic small-bowel findings in celiac disease (intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy) are not pathognomonic, making serology important for diagnosis. European guidelines discuss forgoing biopsy in children whose antitissue transglutaminase antibody titers are at least 10-fold above the upper limit of normal. However, the American College of Gastroenterology and the American Gastroenterological Association continue to recommend combining serology with confirmatory small bowel biopsy. The extent to which physicians follow this advice is unclear, the researchers noted.

Therefore, they analyzed data from a questionnaire posted on the Celiac Disease Foundation website during a 7-month period in 2016. Among 982 adults with self-reported celiac disease, 780 said their diagnosis included both serology and biopsy and 202 said they received serology only. Only 40% of these nonbiopsied respondents said they sought nutritional counseling at diagnosis, compared with 59% of biopsied patients (P less than .001). Patients diagnosed by serology alone also were more likely to report using dietary supplements to aid gluten digestion (20% vs. 9% of biopsied respondents; P less than .001).

These associations remained statistically significant after adjustment for age and sex, said the researchers. Nonbiopsied patients had a significantly lower odds of having been diagnosed by a gastroenterologist (odds ratio, 0.16; 95% confidence interval, 0.07-0.37) and seeking nutritional counseling (OR, 0.45; 95% CI, 0.33-0.63) and were significantly more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19).

Fully 87% of respondents always followed a strict gluten-free diet, but symptoms persisted in 65% of those who were not biopsied, compared with only 51% of those who were biopsied. There were too few responses to this question for the difference between groups to reach statistical significance, but the finding might reflect the greater diagnostic accuracy of biopsy, the researchers said. However, they cautioned that none of the associations in this study were necessarily causal, diagnoses were not independently validated, and the reliability of self-reported celiac diagnosis remains unclear.

Survey respondents also were self-selected – for example, 91% self-identified as white and 60% reported having a bachelor’s degree, compared with only about 77% and one-third of adults captured by U.S. Census Bureau data from 2017.

“Although these characteristics may limit the generalizability of our findings, this study nevertheless reflects a population of celiac disease that is not typically studied, such as those not attending large academic celiac disease centers, and those diagnosed without the involvement of a gastroenterologist,” the researchers wrote. “Future studies are warranted to further characterize this population regarding the long-term consequences of forgoing the duodenal biopsy, and to develop educational interventions to promote evidence-based diagnosis and management of celiac disease.”

SOURCE: Joelson AM et al. Clin Gastroenterol Hepatol. 2018 Sep 10. doi: 10.1016/j.cgh.2018.09.006.

Patients with celiac disease often do not receive a biopsy or nutritional recommendations at diagnosis, according to the findings of a large survey study.

Strikingly, 21% of respondents did not have a confirmatory duodenal biopsy, reported Andrew M. Joelson, MD, of Columbia University Medical Center, New York, and his associates. Gastroenterologists diagnosed 66% of biopsied patients but only 31% of nonbiopsied patients (P less than .001). “Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation,” the researchers wrote in the May issue of Clinical Gastroenterology and Hepatology.

Classic small-bowel findings in celiac disease (intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy) are not pathognomonic, making serology important for diagnosis. European guidelines discuss forgoing biopsy in children whose antitissue transglutaminase antibody titers are at least 10-fold above the upper limit of normal. However, the American College of Gastroenterology and the American Gastroenterological Association continue to recommend combining serology with confirmatory small bowel biopsy. The extent to which physicians follow this advice is unclear, the researchers noted.

Therefore, they analyzed data from a questionnaire posted on the Celiac Disease Foundation website during a 7-month period in 2016. Among 982 adults with self-reported celiac disease, 780 said their diagnosis included both serology and biopsy and 202 said they received serology only. Only 40% of these nonbiopsied respondents said they sought nutritional counseling at diagnosis, compared with 59% of biopsied patients (P less than .001). Patients diagnosed by serology alone also were more likely to report using dietary supplements to aid gluten digestion (20% vs. 9% of biopsied respondents; P less than .001).

These associations remained statistically significant after adjustment for age and sex, said the researchers. Nonbiopsied patients had a significantly lower odds of having been diagnosed by a gastroenterologist (odds ratio, 0.16; 95% confidence interval, 0.07-0.37) and seeking nutritional counseling (OR, 0.45; 95% CI, 0.33-0.63) and were significantly more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19).

Fully 87% of respondents always followed a strict gluten-free diet, but symptoms persisted in 65% of those who were not biopsied, compared with only 51% of those who were biopsied. There were too few responses to this question for the difference between groups to reach statistical significance, but the finding might reflect the greater diagnostic accuracy of biopsy, the researchers said. However, they cautioned that none of the associations in this study were necessarily causal, diagnoses were not independently validated, and the reliability of self-reported celiac diagnosis remains unclear.

Survey respondents also were self-selected – for example, 91% self-identified as white and 60% reported having a bachelor’s degree, compared with only about 77% and one-third of adults captured by U.S. Census Bureau data from 2017.

“Although these characteristics may limit the generalizability of our findings, this study nevertheless reflects a population of celiac disease that is not typically studied, such as those not attending large academic celiac disease centers, and those diagnosed without the involvement of a gastroenterologist,” the researchers wrote. “Future studies are warranted to further characterize this population regarding the long-term consequences of forgoing the duodenal biopsy, and to develop educational interventions to promote evidence-based diagnosis and management of celiac disease.”

SOURCE: Joelson AM et al. Clin Gastroenterol Hepatol. 2018 Sep 10. doi: 10.1016/j.cgh.2018.09.006.

In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.

When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.

In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.

Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.

The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.

“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.

Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.

SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.

In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.

When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.

In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.

Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.

The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.

“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.

Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.

SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.

In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.

When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.

In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.

Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.

The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.

“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.

Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.

SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.

SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.