NEW ORLEANS – It wasn’t until her teenage daughter wanted to get her belly button pierced that Cora Breuner, MD, became interested in the safety of tattoos and piercings for adolescents.

“You’re a pediatrician,” her daughter said. “Where should I go? Should I get this done?” Although Dr. Breuner didn’t want her daughter to get the piercing, she knew saying “no” wasn’t likely to stop her teenager any more than it would another adolescent, so she looked to the medical literature … and didn’t find much.

“I couldn’t find an article summarizing complication rates or just about the legality of it or other issues around tattooing and piercing,” said Dr. Breuner a professor of pediatrics at Seattle Children’s Hospital and the University of Washington, also in Seattle. So she and the American Academy of Pediatrics’ Committee on Adolescent Health did the work themselves and wrote one.

Now she recommends that all health care workers treating children ask their adolescent patients about tattoos and piercings at every health care visit. “I want to make sure that you are talking to your teenagers about this,” she told attendees at the annual meeting of the American Academy of Pediatrics. In her presentation, she focused on knowing the legal age of consent for body modifications and what to watch for in terms of complications.
 

Tattoos growing in popularity

More than a third (38%) of people aged 18-29 years have at least one tattoo, according to a Pew Research Center report Dr. Breuner cited, and 23% had piercings somewhere on their body besides their ears. In fact, Americans spend about $1.65 billion on tattoos each year.

Most of the people with tattoos (72%), however, had them in places that were covered and not visible, reinforcing the need to ask about them. The popularity of tattoos has been increasing in general, Dr. Breuner noted. In just the 4 years from 2012 to 2016, the prevalence of U.S. adults with at least one tattoo increased 20%.

And people don’t appear to be sorry to have them. According to a Harris Poll that Dr. Breuner cited, 86% of respondents in 2012 did not regret getting their tattoo, and respondents listed a number of feelings they associated with their tattoos: feeling sexy, rebellious, attractive, strong, spiritual, healthier, intelligent, and athletic.

Although the techniques for tattooing have changed over the years since the first documented ones in 4,000 B.C., the basic concept of injecting ink into the dermis hasn’t changed much. By injecting the ink below the epidermis, the ink remains visible for the rest of a person’s life.

Courtesy Annie Fulton

The laws for tattoos vary by state, so you need to check the laws where they live. Not much data exist on infections and complaints, but data from the Michigan Department of Health & Human Services suggests the infection rate – at least those infections reported – is low while the rate of illegally operating facilities is a bigger risk. Local health districts in Michigan have received reports of only 18 infections since 2010, but they’ve received 85 reports of illegal operations and 69 reports of social media parties centered on all attendees getting a tattoo.
 

Risks of tattoos

The biggest concern for adolescents is ensuring they understand the risks of tattoos and piercings and what to look for. One risk for tattoos is hepatitis C. However, the studies on the risk of contracting hepatitis C from tattooing are confounded by the fact that many people getting tattoos also may be engaging in other risky behaviors, such as intravenous drug use or risky sexual behaviors. Still, some research suggests that “commercially acquired tattoos accounted for more than twice as many infections as injection-drug use,” Dr. Breuner said.

Another risk is tattoo-associated bacterial skin infections (Clin Infect Dis. 2019 Aug 30;69[6]:949-55; MMWR Morb Mortal Wkly Rep. 2012 Aug 24;61[33]:653-6).
 

Risks of body piercing

Although body piercing doesn’t date back quite as far as tattoos – about 700 A.D. – its history remains long. Research suggests the top reason people get body piercings is simply liking the way it looks, as 77% of respondents reported in one study (J Am Osteopath Assoc. 2007 Oct;107[10]:432-8). Other reasons including looking fashionable, catching attention, feeling different, making a personal statement, being daring, fitting in, pressuring from peers, and defying parents.

The most serious potential complication from piercings is gangrene, but the most common is infection. Other possible complications include an allergic reaction to the metal used, a bleeding complication (estimated in 1 of 10), a scar or site reaction (estimated in 1 of 15), or, much less commonly, toxic shock syndrome. In some areas, there’s a risk of nerve damage if the nerve is pierced, such as in the eyebrow or in the bridge of the nose.

Teens particularly should be aware of the average time it takes for a piercing to heal, depending on where they get it. A navel piercing, for example, can take up to 9 months to heal. Others with long healing times include the penis (3-9 months), labia majora (2-4 months), nipple (2-4 months), and scrotum (2-3 months). Other non-ear regions range from 2 to 8 weeks.

Bleeding definitely is a risk for piercings, Dr. Breuner said, especially now that so many teens are piercing body parts besides their ears. “The one I found most disturbing was that of the uvula,” she said. Bleeding risks tend to be low with ear and nose piercings, but the risk increases with the tongue, uvula, navel, nipples, and genitalia.

Another risk of mouth piercings, particularly tongue piercing, is damage to the teeth and gums, Dr. Breuner said. Barbells, the most popular type of mouth piercing, can lead to receding gums and chipped teeth with extended wear, especially because people wearing them have a tendency to frequently bite down on them.

One study found that half the participants who wore a long barbell piercing (1.59 cm or longer) for at least 2 years had lingual recession on their mandibular central incisors (J Periodontol. 2002 Mar;73[3]:289-97). Among those with a tongue piercing of at least 4 years, 47% had tooth chipping on their molars and premolars.

Another study found gingival recession was 11 times more likely among people with tongue piercings than without (J Clin Periodontol. 2010 Aug 1;37(8):712-8). Gingival recession also is a risk with lip piercings, but the risk is greater with tongue piercing, and only tongue piercings have been associated with tooth injuries (Aust Dent J. 2012 Mar;57[1]:71-8; Int J Dent Hyg. 2016 Feb;14[1]:62-73).

Hepatitis C also is a concern with body piercing. According to a systematic review of 12 studies, body piercing was a risk factor for hepatitis C infection in the majority of them (Am J Infect Control. 2001 Aug;29[4]:271-4).
 

Counseling adolescents on body modifications

You should ask teens about any tattoos or piercings they have at each visit and ask whether they have any plans to get any. Then you can answer questions about them and ensure the teens are aware of risks, particularly viral and bacterial infections and, with piercing, bleeding.

Beyond the medical risks, it’s important for teens to understand that tattoos have the potential to limit their employment in the future, depending on the job and how visible their tattoo is.

Social acceptance of tattoos and piercings have been increasing, but a survey of nearly 2,700 people conducted by Salary.com in 2013 found that 76% of respondents believed tattoos and piercings could reduce a job applicant’s chances of being hired.

If you want to learn more specifically about the safest places in your community for tattoos and piercings, Dr. Breuner recommended going out and visiting the shops. Tattoo artists generally are the most knowledgeable people in the community about the risks of their industry and often welcome local physicians who want to learn and see their equipment, she said.

NEW ORLEANS – It wasn’t until her teenage daughter wanted to get her belly button pierced that Cora Breuner, MD, became interested in the safety of tattoos and piercings for adolescents.

“You’re a pediatrician,” her daughter said. “Where should I go? Should I get this done?” Although Dr. Breuner didn’t want her daughter to get the piercing, she knew saying “no” wasn’t likely to stop her teenager any more than it would another adolescent, so she looked to the medical literature … and didn’t find much.

“I couldn’t find an article summarizing complication rates or just about the legality of it or other issues around tattooing and piercing,” said Dr. Breuner a professor of pediatrics at Seattle Children’s Hospital and the University of Washington, also in Seattle. So she and the American Academy of Pediatrics’ Committee on Adolescent Health did the work themselves and wrote one.

Now she recommends that all health care workers treating children ask their adolescent patients about tattoos and piercings at every health care visit. “I want to make sure that you are talking to your teenagers about this,” she told attendees at the annual meeting of the American Academy of Pediatrics. In her presentation, she focused on knowing the legal age of consent for body modifications and what to watch for in terms of complications.
 

Tattoos growing in popularity

More than a third (38%) of people aged 18-29 years have at least one tattoo, according to a Pew Research Center report Dr. Breuner cited, and 23% had piercings somewhere on their body besides their ears. In fact, Americans spend about $1.65 billion on tattoos each year.

Most of the people with tattoos (72%), however, had them in places that were covered and not visible, reinforcing the need to ask about them. The popularity of tattoos has been increasing in general, Dr. Breuner noted. In just the 4 years from 2012 to 2016, the prevalence of U.S. adults with at least one tattoo increased 20%.

And people don’t appear to be sorry to have them. According to a Harris Poll that Dr. Breuner cited, 86% of respondents in 2012 did not regret getting their tattoo, and respondents listed a number of feelings they associated with their tattoos: feeling sexy, rebellious, attractive, strong, spiritual, healthier, intelligent, and athletic.

Although the techniques for tattooing have changed over the years since the first documented ones in 4,000 B.C., the basic concept of injecting ink into the dermis hasn’t changed much. By injecting the ink below the epidermis, the ink remains visible for the rest of a person’s life.

Courtesy Annie Fulton

The laws for tattoos vary by state, so you need to check the laws where they live. Not much data exist on infections and complaints, but data from the Michigan Department of Health & Human Services suggests the infection rate – at least those infections reported – is low while the rate of illegally operating facilities is a bigger risk. Local health districts in Michigan have received reports of only 18 infections since 2010, but they’ve received 85 reports of illegal operations and 69 reports of social media parties centered on all attendees getting a tattoo.
 

Risks of tattoos

The biggest concern for adolescents is ensuring they understand the risks of tattoos and piercings and what to look for. One risk for tattoos is hepatitis C. However, the studies on the risk of contracting hepatitis C from tattooing are confounded by the fact that many people getting tattoos also may be engaging in other risky behaviors, such as intravenous drug use or risky sexual behaviors. Still, some research suggests that “commercially acquired tattoos accounted for more than twice as many infections as injection-drug use,” Dr. Breuner said.

Another risk is tattoo-associated bacterial skin infections (Clin Infect Dis. 2019 Aug 30;69[6]:949-55; MMWR Morb Mortal Wkly Rep. 2012 Aug 24;61[33]:653-6).
 

Risks of body piercing

Although body piercing doesn’t date back quite as far as tattoos – about 700 A.D. – its history remains long. Research suggests the top reason people get body piercings is simply liking the way it looks, as 77% of respondents reported in one study (J Am Osteopath Assoc. 2007 Oct;107[10]:432-8). Other reasons including looking fashionable, catching attention, feeling different, making a personal statement, being daring, fitting in, pressuring from peers, and defying parents.

The most serious potential complication from piercings is gangrene, but the most common is infection. Other possible complications include an allergic reaction to the metal used, a bleeding complication (estimated in 1 of 10), a scar or site reaction (estimated in 1 of 15), or, much less commonly, toxic shock syndrome. In some areas, there’s a risk of nerve damage if the nerve is pierced, such as in the eyebrow or in the bridge of the nose.

Teens particularly should be aware of the average time it takes for a piercing to heal, depending on where they get it. A navel piercing, for example, can take up to 9 months to heal. Others with long healing times include the penis (3-9 months), labia majora (2-4 months), nipple (2-4 months), and scrotum (2-3 months). Other non-ear regions range from 2 to 8 weeks.

Bleeding definitely is a risk for piercings, Dr. Breuner said, especially now that so many teens are piercing body parts besides their ears. “The one I found most disturbing was that of the uvula,” she said. Bleeding risks tend to be low with ear and nose piercings, but the risk increases with the tongue, uvula, navel, nipples, and genitalia.

Another risk of mouth piercings, particularly tongue piercing, is damage to the teeth and gums, Dr. Breuner said. Barbells, the most popular type of mouth piercing, can lead to receding gums and chipped teeth with extended wear, especially because people wearing them have a tendency to frequently bite down on them.

One study found that half the participants who wore a long barbell piercing (1.59 cm or longer) for at least 2 years had lingual recession on their mandibular central incisors (J Periodontol. 2002 Mar;73[3]:289-97). Among those with a tongue piercing of at least 4 years, 47% had tooth chipping on their molars and premolars.

Another study found gingival recession was 11 times more likely among people with tongue piercings than without (J Clin Periodontol. 2010 Aug 1;37(8):712-8). Gingival recession also is a risk with lip piercings, but the risk is greater with tongue piercing, and only tongue piercings have been associated with tooth injuries (Aust Dent J. 2012 Mar;57[1]:71-8; Int J Dent Hyg. 2016 Feb;14[1]:62-73).

Hepatitis C also is a concern with body piercing. According to a systematic review of 12 studies, body piercing was a risk factor for hepatitis C infection in the majority of them (Am J Infect Control. 2001 Aug;29[4]:271-4).
 

Counseling adolescents on body modifications

You should ask teens about any tattoos or piercings they have at each visit and ask whether they have any plans to get any. Then you can answer questions about them and ensure the teens are aware of risks, particularly viral and bacterial infections and, with piercing, bleeding.

Beyond the medical risks, it’s important for teens to understand that tattoos have the potential to limit their employment in the future, depending on the job and how visible their tattoo is.

Social acceptance of tattoos and piercings have been increasing, but a survey of nearly 2,700 people conducted by Salary.com in 2013 found that 76% of respondents believed tattoos and piercings could reduce a job applicant’s chances of being hired.

If you want to learn more specifically about the safest places in your community for tattoos and piercings, Dr. Breuner recommended going out and visiting the shops. Tattoo artists generally are the most knowledgeable people in the community about the risks of their industry and often welcome local physicians who want to learn and see their equipment, she said.

NEW ORLEANS – It wasn’t until her teenage daughter wanted to get her belly button pierced that Cora Breuner, MD, became interested in the safety of tattoos and piercings for adolescents.

“You’re a pediatrician,” her daughter said. “Where should I go? Should I get this done?” Although Dr. Breuner didn’t want her daughter to get the piercing, she knew saying “no” wasn’t likely to stop her teenager any more than it would another adolescent, so she looked to the medical literature … and didn’t find much.

“I couldn’t find an article summarizing complication rates or just about the legality of it or other issues around tattooing and piercing,” said Dr. Breuner a professor of pediatrics at Seattle Children’s Hospital and the University of Washington, also in Seattle. So she and the American Academy of Pediatrics’ Committee on Adolescent Health did the work themselves and wrote one.

Now she recommends that all health care workers treating children ask their adolescent patients about tattoos and piercings at every health care visit. “I want to make sure that you are talking to your teenagers about this,” she told attendees at the annual meeting of the American Academy of Pediatrics. In her presentation, she focused on knowing the legal age of consent for body modifications and what to watch for in terms of complications.
 

Tattoos growing in popularity

More than a third (38%) of people aged 18-29 years have at least one tattoo, according to a Pew Research Center report Dr. Breuner cited, and 23% had piercings somewhere on their body besides their ears. In fact, Americans spend about $1.65 billion on tattoos each year.

Most of the people with tattoos (72%), however, had them in places that were covered and not visible, reinforcing the need to ask about them. The popularity of tattoos has been increasing in general, Dr. Breuner noted. In just the 4 years from 2012 to 2016, the prevalence of U.S. adults with at least one tattoo increased 20%.

And people don’t appear to be sorry to have them. According to a Harris Poll that Dr. Breuner cited, 86% of respondents in 2012 did not regret getting their tattoo, and respondents listed a number of feelings they associated with their tattoos: feeling sexy, rebellious, attractive, strong, spiritual, healthier, intelligent, and athletic.

Although the techniques for tattooing have changed over the years since the first documented ones in 4,000 B.C., the basic concept of injecting ink into the dermis hasn’t changed much. By injecting the ink below the epidermis, the ink remains visible for the rest of a person’s life.

Courtesy Annie Fulton

The laws for tattoos vary by state, so you need to check the laws where they live. Not much data exist on infections and complaints, but data from the Michigan Department of Health & Human Services suggests the infection rate – at least those infections reported – is low while the rate of illegally operating facilities is a bigger risk. Local health districts in Michigan have received reports of only 18 infections since 2010, but they’ve received 85 reports of illegal operations and 69 reports of social media parties centered on all attendees getting a tattoo.
 

Risks of tattoos

The biggest concern for adolescents is ensuring they understand the risks of tattoos and piercings and what to look for. One risk for tattoos is hepatitis C. However, the studies on the risk of contracting hepatitis C from tattooing are confounded by the fact that many people getting tattoos also may be engaging in other risky behaviors, such as intravenous drug use or risky sexual behaviors. Still, some research suggests that “commercially acquired tattoos accounted for more than twice as many infections as injection-drug use,” Dr. Breuner said.

Another risk is tattoo-associated bacterial skin infections (Clin Infect Dis. 2019 Aug 30;69[6]:949-55; MMWR Morb Mortal Wkly Rep. 2012 Aug 24;61[33]:653-6).
 

Risks of body piercing

Although body piercing doesn’t date back quite as far as tattoos – about 700 A.D. – its history remains long. Research suggests the top reason people get body piercings is simply liking the way it looks, as 77% of respondents reported in one study (J Am Osteopath Assoc. 2007 Oct;107[10]:432-8). Other reasons including looking fashionable, catching attention, feeling different, making a personal statement, being daring, fitting in, pressuring from peers, and defying parents.

The most serious potential complication from piercings is gangrene, but the most common is infection. Other possible complications include an allergic reaction to the metal used, a bleeding complication (estimated in 1 of 10), a scar or site reaction (estimated in 1 of 15), or, much less commonly, toxic shock syndrome. In some areas, there’s a risk of nerve damage if the nerve is pierced, such as in the eyebrow or in the bridge of the nose.

Teens particularly should be aware of the average time it takes for a piercing to heal, depending on where they get it. A navel piercing, for example, can take up to 9 months to heal. Others with long healing times include the penis (3-9 months), labia majora (2-4 months), nipple (2-4 months), and scrotum (2-3 months). Other non-ear regions range from 2 to 8 weeks.

Bleeding definitely is a risk for piercings, Dr. Breuner said, especially now that so many teens are piercing body parts besides their ears. “The one I found most disturbing was that of the uvula,” she said. Bleeding risks tend to be low with ear and nose piercings, but the risk increases with the tongue, uvula, navel, nipples, and genitalia.

Another risk of mouth piercings, particularly tongue piercing, is damage to the teeth and gums, Dr. Breuner said. Barbells, the most popular type of mouth piercing, can lead to receding gums and chipped teeth with extended wear, especially because people wearing them have a tendency to frequently bite down on them.

One study found that half the participants who wore a long barbell piercing (1.59 cm or longer) for at least 2 years had lingual recession on their mandibular central incisors (J Periodontol. 2002 Mar;73[3]:289-97). Among those with a tongue piercing of at least 4 years, 47% had tooth chipping on their molars and premolars.

Another study found gingival recession was 11 times more likely among people with tongue piercings than without (J Clin Periodontol. 2010 Aug 1;37(8):712-8). Gingival recession also is a risk with lip piercings, but the risk is greater with tongue piercing, and only tongue piercings have been associated with tooth injuries (Aust Dent J. 2012 Mar;57[1]:71-8; Int J Dent Hyg. 2016 Feb;14[1]:62-73).

Hepatitis C also is a concern with body piercing. According to a systematic review of 12 studies, body piercing was a risk factor for hepatitis C infection in the majority of them (Am J Infect Control. 2001 Aug;29[4]:271-4).
 

Counseling adolescents on body modifications

You should ask teens about any tattoos or piercings they have at each visit and ask whether they have any plans to get any. Then you can answer questions about them and ensure the teens are aware of risks, particularly viral and bacterial infections and, with piercing, bleeding.

Beyond the medical risks, it’s important for teens to understand that tattoos have the potential to limit their employment in the future, depending on the job and how visible their tattoo is.

Social acceptance of tattoos and piercings have been increasing, but a survey of nearly 2,700 people conducted by Salary.com in 2013 found that 76% of respondents believed tattoos and piercings could reduce a job applicant’s chances of being hired.

If you want to learn more specifically about the safest places in your community for tattoos and piercings, Dr. Breuner recommended going out and visiting the shops. Tattoo artists generally are the most knowledgeable people in the community about the risks of their industry and often welcome local physicians who want to learn and see their equipment, she said.

SAN ANTONIO – Oral supplementation with a proprietary blend of human milk oligosaccharides improved all of the core symptoms of irritable bowel syndrome in a large open-label study, Magnus Simren, MD, PhD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The human milk oligosaccharides (HMOs) were well tolerated, too. Only 2.5% of 317 study participants at 17 U.S. sites discontinued the 12-week study because of side effects, which consisted of flatulence and other mild gastrointestinal symptoms, noted Dr. Simren, a gastroenterologist and professor of medicine at the University of Gothenburg (Sweden).

These positive study results are consistent with the notion that an altered gut microbiota plays a pathophysiological role in irritable bowel syndrome (IBS).

“The challenge is to identify suitable interventions that restore intestinal microbiota composition and functioning,” Dr. Simren observed.

Oral HMOs show promise as one such intervention. In prior small proof-of-concept studies, Dr. Simren and his coworkers demonstrated that HMOs increased gut levels of Bifidobacteria, which are microorganisms important to a healthy gut and are depleted in IBS. The investigators also established that HMOs increased levels of metabolites essential for the gut’s barrier and immune functions.

HMOs are the third-largest constituent in human breast milk. Interest in their potential therapeutic application in IBS grew out of earlier pediatric work demonstrating that HMOs are of great importance in infant health: They bind pathogens and promote gut barrier maturation and immune function.

Dr. Simren reported on 317 patients who met Rome IV criteria for IBS. Nearly two-thirds of them had severe IBS based upon an IBS–Symptom Severity Score above 300. Another third had moderate IBS. Subjects were instructed to take 5 g/day of a 4:1 mix of the HMOs 2’-fucosyllactose and lacto-N-neotetraose, a proprietary nutritional support product available over the counter as Holigos. Participants remained on stable background medications throughout the 12-week study, during which they were evaluated every 4 weeks.

The primary outcome was the effect of daily oral consumption of HMOs on stool consistency as assessed using the Bristol Stool Form Scale. At baseline, 50.3% of subjects had IBS constipation as defined by Bristol type 1-2 stools. By week 4, the proportion of patients with constipation dropped to 32.9%, and at weeks 8 and 12, just under 31%. Similarly, the proportion of patients with diarrhea as reflected in Bristol type 6-7 stools quickly improved from 40.4% at baseline to 27.5% at week 4 and 26% thereafter. Meanwhile, the proportion of patients with normal stools on the Bristol scale jumped from 9.3% at baseline to 39.6% at week 4 and nearly 43% thereafter.

About 77% of patients reported a significant reduction in symptom severity within 4 weeks, and 87% did so by 12 weeks. Bloating decreased by 59%, as did abdominal pain severity. In addition, scores on the IBS Quality of Life Scale improved by 48%.

The observed improvements in symptoms and quality of life were consistent across all IBS subtypes.

“Of course, the next step now is to perform a randomized, placebo-controlled, double-blind study to see if these encouraging results can be confirmed in that setting,” Dr. Simren commented.

Session comoderator Brooks D. Cash, MD, of the University of Texas, Houston, called the HMO study “very provocative” and declared he is looking forward to the randomized, controlled trial, which he hopes will assess the long-term durability of the treatment benefits. That trial is still in the planning stages.

Dr. Simren reported serving on an advisory board for Glycom, the Danish company which markets Holigos and sponsored the open-label U.S. study.

[email protected]

SAN ANTONIO – Oral supplementation with a proprietary blend of human milk oligosaccharides improved all of the core symptoms of irritable bowel syndrome in a large open-label study, Magnus Simren, MD, PhD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The human milk oligosaccharides (HMOs) were well tolerated, too. Only 2.5% of 317 study participants at 17 U.S. sites discontinued the 12-week study because of side effects, which consisted of flatulence and other mild gastrointestinal symptoms, noted Dr. Simren, a gastroenterologist and professor of medicine at the University of Gothenburg (Sweden).

These positive study results are consistent with the notion that an altered gut microbiota plays a pathophysiological role in irritable bowel syndrome (IBS).

“The challenge is to identify suitable interventions that restore intestinal microbiota composition and functioning,” Dr. Simren observed.

Oral HMOs show promise as one such intervention. In prior small proof-of-concept studies, Dr. Simren and his coworkers demonstrated that HMOs increased gut levels of Bifidobacteria, which are microorganisms important to a healthy gut and are depleted in IBS. The investigators also established that HMOs increased levels of metabolites essential for the gut’s barrier and immune functions.

HMOs are the third-largest constituent in human breast milk. Interest in their potential therapeutic application in IBS grew out of earlier pediatric work demonstrating that HMOs are of great importance in infant health: They bind pathogens and promote gut barrier maturation and immune function.

Dr. Simren reported on 317 patients who met Rome IV criteria for IBS. Nearly two-thirds of them had severe IBS based upon an IBS–Symptom Severity Score above 300. Another third had moderate IBS. Subjects were instructed to take 5 g/day of a 4:1 mix of the HMOs 2’-fucosyllactose and lacto-N-neotetraose, a proprietary nutritional support product available over the counter as Holigos. Participants remained on stable background medications throughout the 12-week study, during which they were evaluated every 4 weeks.

The primary outcome was the effect of daily oral consumption of HMOs on stool consistency as assessed using the Bristol Stool Form Scale. At baseline, 50.3% of subjects had IBS constipation as defined by Bristol type 1-2 stools. By week 4, the proportion of patients with constipation dropped to 32.9%, and at weeks 8 and 12, just under 31%. Similarly, the proportion of patients with diarrhea as reflected in Bristol type 6-7 stools quickly improved from 40.4% at baseline to 27.5% at week 4 and 26% thereafter. Meanwhile, the proportion of patients with normal stools on the Bristol scale jumped from 9.3% at baseline to 39.6% at week 4 and nearly 43% thereafter.

About 77% of patients reported a significant reduction in symptom severity within 4 weeks, and 87% did so by 12 weeks. Bloating decreased by 59%, as did abdominal pain severity. In addition, scores on the IBS Quality of Life Scale improved by 48%.

The observed improvements in symptoms and quality of life were consistent across all IBS subtypes.

“Of course, the next step now is to perform a randomized, placebo-controlled, double-blind study to see if these encouraging results can be confirmed in that setting,” Dr. Simren commented.

Session comoderator Brooks D. Cash, MD, of the University of Texas, Houston, called the HMO study “very provocative” and declared he is looking forward to the randomized, controlled trial, which he hopes will assess the long-term durability of the treatment benefits. That trial is still in the planning stages.

Dr. Simren reported serving on an advisory board for Glycom, the Danish company which markets Holigos and sponsored the open-label U.S. study.

[email protected]

SAN ANTONIO – Oral supplementation with a proprietary blend of human milk oligosaccharides improved all of the core symptoms of irritable bowel syndrome in a large open-label study, Magnus Simren, MD, PhD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The human milk oligosaccharides (HMOs) were well tolerated, too. Only 2.5% of 317 study participants at 17 U.S. sites discontinued the 12-week study because of side effects, which consisted of flatulence and other mild gastrointestinal symptoms, noted Dr. Simren, a gastroenterologist and professor of medicine at the University of Gothenburg (Sweden).

These positive study results are consistent with the notion that an altered gut microbiota plays a pathophysiological role in irritable bowel syndrome (IBS).

“The challenge is to identify suitable interventions that restore intestinal microbiota composition and functioning,” Dr. Simren observed.

Oral HMOs show promise as one such intervention. In prior small proof-of-concept studies, Dr. Simren and his coworkers demonstrated that HMOs increased gut levels of Bifidobacteria, which are microorganisms important to a healthy gut and are depleted in IBS. The investigators also established that HMOs increased levels of metabolites essential for the gut’s barrier and immune functions.

HMOs are the third-largest constituent in human breast milk. Interest in their potential therapeutic application in IBS grew out of earlier pediatric work demonstrating that HMOs are of great importance in infant health: They bind pathogens and promote gut barrier maturation and immune function.

Dr. Simren reported on 317 patients who met Rome IV criteria for IBS. Nearly two-thirds of them had severe IBS based upon an IBS–Symptom Severity Score above 300. Another third had moderate IBS. Subjects were instructed to take 5 g/day of a 4:1 mix of the HMOs 2’-fucosyllactose and lacto-N-neotetraose, a proprietary nutritional support product available over the counter as Holigos. Participants remained on stable background medications throughout the 12-week study, during which they were evaluated every 4 weeks.

The primary outcome was the effect of daily oral consumption of HMOs on stool consistency as assessed using the Bristol Stool Form Scale. At baseline, 50.3% of subjects had IBS constipation as defined by Bristol type 1-2 stools. By week 4, the proportion of patients with constipation dropped to 32.9%, and at weeks 8 and 12, just under 31%. Similarly, the proportion of patients with diarrhea as reflected in Bristol type 6-7 stools quickly improved from 40.4% at baseline to 27.5% at week 4 and 26% thereafter. Meanwhile, the proportion of patients with normal stools on the Bristol scale jumped from 9.3% at baseline to 39.6% at week 4 and nearly 43% thereafter.

About 77% of patients reported a significant reduction in symptom severity within 4 weeks, and 87% did so by 12 weeks. Bloating decreased by 59%, as did abdominal pain severity. In addition, scores on the IBS Quality of Life Scale improved by 48%.

The observed improvements in symptoms and quality of life were consistent across all IBS subtypes.

“Of course, the next step now is to perform a randomized, placebo-controlled, double-blind study to see if these encouraging results can be confirmed in that setting,” Dr. Simren commented.

Session comoderator Brooks D. Cash, MD, of the University of Texas, Houston, called the HMO study “very provocative” and declared he is looking forward to the randomized, controlled trial, which he hopes will assess the long-term durability of the treatment benefits. That trial is still in the planning stages.

Dr. Simren reported serving on an advisory board for Glycom, the Danish company which markets Holigos and sponsored the open-label U.S. study.

[email protected]

SAN ANTONIO – Maintenance therapy with the immune checkpoint inhibitor durvalumab (Imfinzi) did not improve outcomes compared with chemotherapy for patients with metastatic breast cancer, although there was a trend toward benefit for patients with triple-negative breast cancer and those whose tumors were positive for programmed death ligand 1 (PD-L1), a substudy of SAFIR-02 Breast.

Neil Osterweil/MDedge News

Median progression-free survival for 131 patients with metastatic or locally advanced, HER2-negative, hormone receptor–negative or endocrine-resistant breast cancer who received durvalumab maintenance following chemotherapy in the study was 2.7 months, compared with 4.4 months for 68 patients who received maintenance chemotherapy, reported Florence Dalenc, MD, of Institut Claudius Regaud, Toulouse, France.

“For hormone receptor–positive metastatic breast cancer, exploratory analyses suggest that anti-PD-L1 as a single agent is less effective than chemotherapy as maintenance,” she said at the San Antonio Breast Cancer Symposium.

The rationale for investigating an anti-PD-L1 agent for maintenance in patients with metastatic breast cancer is that the tumor is (presumably) not growing when immunotherapy is introduced and disease burden, a mechanism of immune suppression, has been reduced by chemotherapy. In addition, chemotherapy attracts tumor infiltrating lymphocytes (TILs) to the tumor bed, and response to chemotherapy may be a marker for immunogenic tumors, she said.

Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of the programmed death protein 1 with PD-L1. In the GeparNuevo trial, the addition of durvalumab to anthracycline-/taxane-based neoadjuvant chemotherapy increased the pathologic complete response (pCR) rate particularly in patients treated with durvalumab alone before the start of chemotherapy.

To see whether durvalumab could offer a benefit over chemotherapy in the maintenance setting, Dr. Dalenc and colleagues studied patients who were enrolled in SAFIR-02 Breast, which was designed to assess the efficacy of genomic analysis as a therapeutic decision tool in patients with metastatic breast cancer.

In the trial, patients with HER2-negative metastatic breast cancer who have a complete or partial response or stable disease following six to eight chemotherapy cycles (or 4 cycles if chemotherapy was stopped for toxicities) are randomized based on the presence or absence of targetable molecular alterations. Patients with identified alteration are then randomized to either targeted therapy matched to genomics, or to maintenance chemotherapy.

Patients without molecular alterations – the population included in the SAFIR02-IMMUNO substudy reported by Dr. Dalenc and colleagues – are stratified by one or two prior lines of chemotherapy and by response type, and then stratified on a 2:1 basis to maintenance with either durvalumab 10 mg/kg every 14 days or standard maintenance chemotherapy for up to 2 years.

In each arm, the median patient age was 56, and approximately 58% of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0. Approximately 43% of patients in each arm had three or more metastatic sites, and roughly half had liver metastases, while slightly more than one-fourth had metastases to lung.

As noted before, median PFS in the overall substudy population, the primary endpoint, was 4.6 months for patients on maintenance chemotherapy, compared with 2.7 months with durvalumab. This difference translated into an adjusted hazard ratio for progression with durvalumab of 1.40 (P = .047).

Also as noted, there were nonsignificant trends toward benefit with durvalumab among patients with triple-negative breast cancer or PD-L1-positive tumors. For all other subgroups, however, maintenance chemotherapy was favored, with significant benefit seen among patients with disease that progressed after second-line chemotherapy, patients with a clinical response at the time of re-randomization, those 50 years and older, patients with non-triple-negative disease, patients with liver metastases, and those whose tumors were negative for PD-L1.

Median overall survival (OS) was numerically longer with durvalumab (21.7 vs. 17.9 months), but this difference was not statistically significant.

In exploratory analyses, median OS for patients with triple-negative disease was 21 vs. 14 months, respectively, with an unadjusted hazard ratio favoring durvalumab of 0.54 (P = .0377). Among patients with PD-L1 positive tumors, the median OS was 26 months with durvalumab vs. 12 months with chemotherapy, with an unadjusted hazard ratio of 0.42, which just missed statistical significance (P = .0552).

Dr. Dalenc said that the study generates the hypothesis that single-agent durvalumab could improve outcomes in metastatic triple-negative breast cancer, but also raises questions about which disease parameters limit the response to anti-PD-L1 therapy.

The study was sponsored by UNICANCER with support from Fondation ARC and AstraZeneca. Dr. Dalenc reported research grants, travel, and/or advisory board activity for AstraZeneca and others.

SOURCE: Dalenc F et al. SABCS 2019. Abstract GS3-02.

SAN ANTONIO – Maintenance therapy with the immune checkpoint inhibitor durvalumab (Imfinzi) did not improve outcomes compared with chemotherapy for patients with metastatic breast cancer, although there was a trend toward benefit for patients with triple-negative breast cancer and those whose tumors were positive for programmed death ligand 1 (PD-L1), a substudy of SAFIR-02 Breast.

Neil Osterweil/MDedge News

Median progression-free survival for 131 patients with metastatic or locally advanced, HER2-negative, hormone receptor–negative or endocrine-resistant breast cancer who received durvalumab maintenance following chemotherapy in the study was 2.7 months, compared with 4.4 months for 68 patients who received maintenance chemotherapy, reported Florence Dalenc, MD, of Institut Claudius Regaud, Toulouse, France.

“For hormone receptor–positive metastatic breast cancer, exploratory analyses suggest that anti-PD-L1 as a single agent is less effective than chemotherapy as maintenance,” she said at the San Antonio Breast Cancer Symposium.

The rationale for investigating an anti-PD-L1 agent for maintenance in patients with metastatic breast cancer is that the tumor is (presumably) not growing when immunotherapy is introduced and disease burden, a mechanism of immune suppression, has been reduced by chemotherapy. In addition, chemotherapy attracts tumor infiltrating lymphocytes (TILs) to the tumor bed, and response to chemotherapy may be a marker for immunogenic tumors, she said.

Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of the programmed death protein 1 with PD-L1. In the GeparNuevo trial, the addition of durvalumab to anthracycline-/taxane-based neoadjuvant chemotherapy increased the pathologic complete response (pCR) rate particularly in patients treated with durvalumab alone before the start of chemotherapy.

To see whether durvalumab could offer a benefit over chemotherapy in the maintenance setting, Dr. Dalenc and colleagues studied patients who were enrolled in SAFIR-02 Breast, which was designed to assess the efficacy of genomic analysis as a therapeutic decision tool in patients with metastatic breast cancer.

In the trial, patients with HER2-negative metastatic breast cancer who have a complete or partial response or stable disease following six to eight chemotherapy cycles (or 4 cycles if chemotherapy was stopped for toxicities) are randomized based on the presence or absence of targetable molecular alterations. Patients with identified alteration are then randomized to either targeted therapy matched to genomics, or to maintenance chemotherapy.

Patients without molecular alterations – the population included in the SAFIR02-IMMUNO substudy reported by Dr. Dalenc and colleagues – are stratified by one or two prior lines of chemotherapy and by response type, and then stratified on a 2:1 basis to maintenance with either durvalumab 10 mg/kg every 14 days or standard maintenance chemotherapy for up to 2 years.

In each arm, the median patient age was 56, and approximately 58% of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0. Approximately 43% of patients in each arm had three or more metastatic sites, and roughly half had liver metastases, while slightly more than one-fourth had metastases to lung.

As noted before, median PFS in the overall substudy population, the primary endpoint, was 4.6 months for patients on maintenance chemotherapy, compared with 2.7 months with durvalumab. This difference translated into an adjusted hazard ratio for progression with durvalumab of 1.40 (P = .047).

Also as noted, there were nonsignificant trends toward benefit with durvalumab among patients with triple-negative breast cancer or PD-L1-positive tumors. For all other subgroups, however, maintenance chemotherapy was favored, with significant benefit seen among patients with disease that progressed after second-line chemotherapy, patients with a clinical response at the time of re-randomization, those 50 years and older, patients with non-triple-negative disease, patients with liver metastases, and those whose tumors were negative for PD-L1.

Median overall survival (OS) was numerically longer with durvalumab (21.7 vs. 17.9 months), but this difference was not statistically significant.

In exploratory analyses, median OS for patients with triple-negative disease was 21 vs. 14 months, respectively, with an unadjusted hazard ratio favoring durvalumab of 0.54 (P = .0377). Among patients with PD-L1 positive tumors, the median OS was 26 months with durvalumab vs. 12 months with chemotherapy, with an unadjusted hazard ratio of 0.42, which just missed statistical significance (P = .0552).

Dr. Dalenc said that the study generates the hypothesis that single-agent durvalumab could improve outcomes in metastatic triple-negative breast cancer, but also raises questions about which disease parameters limit the response to anti-PD-L1 therapy.

The study was sponsored by UNICANCER with support from Fondation ARC and AstraZeneca. Dr. Dalenc reported research grants, travel, and/or advisory board activity for AstraZeneca and others.

SOURCE: Dalenc F et al. SABCS 2019. Abstract GS3-02.

SAN ANTONIO – Maintenance therapy with the immune checkpoint inhibitor durvalumab (Imfinzi) did not improve outcomes compared with chemotherapy for patients with metastatic breast cancer, although there was a trend toward benefit for patients with triple-negative breast cancer and those whose tumors were positive for programmed death ligand 1 (PD-L1), a substudy of SAFIR-02 Breast.

Neil Osterweil/MDedge News

Median progression-free survival for 131 patients with metastatic or locally advanced, HER2-negative, hormone receptor–negative or endocrine-resistant breast cancer who received durvalumab maintenance following chemotherapy in the study was 2.7 months, compared with 4.4 months for 68 patients who received maintenance chemotherapy, reported Florence Dalenc, MD, of Institut Claudius Regaud, Toulouse, France.

“For hormone receptor–positive metastatic breast cancer, exploratory analyses suggest that anti-PD-L1 as a single agent is less effective than chemotherapy as maintenance,” she said at the San Antonio Breast Cancer Symposium.

The rationale for investigating an anti-PD-L1 agent for maintenance in patients with metastatic breast cancer is that the tumor is (presumably) not growing when immunotherapy is introduced and disease burden, a mechanism of immune suppression, has been reduced by chemotherapy. In addition, chemotherapy attracts tumor infiltrating lymphocytes (TILs) to the tumor bed, and response to chemotherapy may be a marker for immunogenic tumors, she said.

Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of the programmed death protein 1 with PD-L1. In the GeparNuevo trial, the addition of durvalumab to anthracycline-/taxane-based neoadjuvant chemotherapy increased the pathologic complete response (pCR) rate particularly in patients treated with durvalumab alone before the start of chemotherapy.

To see whether durvalumab could offer a benefit over chemotherapy in the maintenance setting, Dr. Dalenc and colleagues studied patients who were enrolled in SAFIR-02 Breast, which was designed to assess the efficacy of genomic analysis as a therapeutic decision tool in patients with metastatic breast cancer.

In the trial, patients with HER2-negative metastatic breast cancer who have a complete or partial response or stable disease following six to eight chemotherapy cycles (or 4 cycles if chemotherapy was stopped for toxicities) are randomized based on the presence or absence of targetable molecular alterations. Patients with identified alteration are then randomized to either targeted therapy matched to genomics, or to maintenance chemotherapy.

Patients without molecular alterations – the population included in the SAFIR02-IMMUNO substudy reported by Dr. Dalenc and colleagues – are stratified by one or two prior lines of chemotherapy and by response type, and then stratified on a 2:1 basis to maintenance with either durvalumab 10 mg/kg every 14 days or standard maintenance chemotherapy for up to 2 years.

In each arm, the median patient age was 56, and approximately 58% of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0. Approximately 43% of patients in each arm had three or more metastatic sites, and roughly half had liver metastases, while slightly more than one-fourth had metastases to lung.

As noted before, median PFS in the overall substudy population, the primary endpoint, was 4.6 months for patients on maintenance chemotherapy, compared with 2.7 months with durvalumab. This difference translated into an adjusted hazard ratio for progression with durvalumab of 1.40 (P = .047).

Also as noted, there were nonsignificant trends toward benefit with durvalumab among patients with triple-negative breast cancer or PD-L1-positive tumors. For all other subgroups, however, maintenance chemotherapy was favored, with significant benefit seen among patients with disease that progressed after second-line chemotherapy, patients with a clinical response at the time of re-randomization, those 50 years and older, patients with non-triple-negative disease, patients with liver metastases, and those whose tumors were negative for PD-L1.

Median overall survival (OS) was numerically longer with durvalumab (21.7 vs. 17.9 months), but this difference was not statistically significant.

In exploratory analyses, median OS for patients with triple-negative disease was 21 vs. 14 months, respectively, with an unadjusted hazard ratio favoring durvalumab of 0.54 (P = .0377). Among patients with PD-L1 positive tumors, the median OS was 26 months with durvalumab vs. 12 months with chemotherapy, with an unadjusted hazard ratio of 0.42, which just missed statistical significance (P = .0552).

Dr. Dalenc said that the study generates the hypothesis that single-agent durvalumab could improve outcomes in metastatic triple-negative breast cancer, but also raises questions about which disease parameters limit the response to anti-PD-L1 therapy.

The study was sponsored by UNICANCER with support from Fondation ARC and AstraZeneca. Dr. Dalenc reported research grants, travel, and/or advisory board activity for AstraZeneca and others.

SOURCE: Dalenc F et al. SABCS 2019. Abstract GS3-02.

In this edition of “How I Will Treat My Next Patient,” I highlight two recent studies that reinforce prior diagnostic and treatment preferences among many oncologists and will certainly influence the discussions we all will have with our patients in the coming weeks and months.

Rituximab maintenance in follicular lymphoma

The largest trial addressing the role of maintenance CD20-targeted antibody therapy was the Primary Rituximab and Maintenance (PRIMA) phase 3, intergroup study in 1,018 advanced follicular lymphoma patients with an initial response to induction chemoimmunotherapy. The induction regimen could be either of three commonly used regimens plus rituximab. Importantly, none of the induction regimens included bendamustine.

Patients were randomized to 2 years of rituximab maintenance or observation. Prior interim analyses at 3 and 6 years showed improvements for the rituximab maintenance patients in progression-free survival and other secondary endpoints, but no improvement in overall survival. Emmanuel Bachy, MD, PhD, and colleagues published the final survival data after 9 years of follow-up, including a final safety analysis (J Clin Oncol. 2019 Nov 1;37[31]:2815-24).

Among the 607 patients consenting to extended follow-up, median progression-free survival was 10.5 years with rituximab maintenance, compared with 4.1 years for observation (hazard ratio, 0.61; P less than .001). There were more patients with progression-free survival at 3 years, complete response or unconfirmed complete response at 2 years, longer time to next antilymphoma treatment, and later time to next chemotherapy. But the 10-year overall survival was similar in the two groups, as were the quality of life ratings.

In all, 503 patients experienced disease progression. Overall survival after progression was shorter in the rituximab maintenance arm versus the observation arm. Among the approximately 4% of patients experiencing transformation from follicular lymphoma to a more aggressive histology, there was no difference observed in time to transformation. Results were independent of the induction regimen received, response to induction, Follicular Lymphoma International Prognostic Index score, and other clinical factors.

In the safety analysis, there were more grade 3-4 adverse events among the rituximab maintenance patients – primarily cytopenia and infections – more serious adverse events, and more adverse events overall. Fatal adverse events were low in both groups (1.6 vs. 0.6%).
 

How these results influence practice

Many years ago, a senior mentor of mine taught that “progression-free survival is an important endpoint since the quality of life for patients is generally superior before relapse than afterwards.”

With that mantra playing in my mind and with the reality that discussions about relapse and subsequent treatment are never easy, the results of PRIMA seem straightforward: Rituximab maintenance is beneficial, despite the absence of an overall survival benefit, in a disease with multiple options for subsequent therapy and a long natural history. In this 9-year, final analysis of PRIMA, rituximab maintenance seems to have achieved its goals of deepening responses with low (but not inconsequential) toxicity and delaying substantially those difficult conversations with patients about how to proceed after relapse.

The influence of the final analysis of PRIMA, however, may be more complicated that it would initially seem. Bendamustine-containing regimens were not employed, are commonly used now, and some studies with bendamustine have suggested higher nonrelapse mortality with rituximab maintenance.

Low-grade adverse events take on greater importance for patients on long-term therapy than they do for patients receiving abbreviated treatment, and with noncurative treatment, the higher adverse event profile with 2 years of rituximab maintenance needs to be taken seriously. Induction and maintenance regimens involving rituximab alone, lenalidomide, or obinutuzumab may be preferred for some patients. For all of those reasons, the discussion about rituximab with advanced follicular lymphoma patients remains a long one, demanding detailed descriptions of risks, benefits, limitations of the data, and multiple modern day alternatives to the treatments employed in PRIMA.
 

Supplemental MRI for dense breast tissue

In the DENSE trial, investigators assigned 40,373 women with extremely dense breast tissue and negative results on screening mammography to be offered either supplemental MRI or mammography screening every other year only. The women were 50-75 years old and were enrolled in the Dutch population-based digital mammography screening program. The primary outcome was the difference in the number of cancers that developed in the 2-year interval between mammograms (N Engl J Med 2019;381:2091-102).

The interval cancer rate was 2.5 per 1,000 screenings among 4,783 women in the “MRI-invitation” group (41% of whom did not actually agree to have an MRI), and 5 per 1,000 in the 32,312 women in the “mammography-only” group, a difference of 2.5 per 1,000 screenings (P less than .001).

Of the 20 interval cancers diagnosed in the MRI-invitation group, 4 were diagnosed in the 59% of women who had undergone MRI (0.8 per 1,000 screenings). The remaining 16 were diagnosed in those who had declined an MRI (4.9 per 1,000 screenings) – virtually identical to the rate of interval cancers in the group that was not invited to have an MRI. This speaks against nonrandom allocation of patients between the mammography-only and the supplemental MRI groups.

Although supplemental MRI was associated with a cancer-detection rate of 16.5 per 1,000 screenings, there was a false positive rate of 8.0% (79.8 per 1,000 screenings). Of the women who underwent a breast biopsy after MRI, 73.7% did not have cancer. Among the women who had MRI-detected cancers, in general, the malignancies diagnosed were smaller, more likely node negative, better differentiated, and more often hormone receptor–positive, compared with those in the mammography-only group.

At the next screening mammogram, the cancer detection rate was lower in the MRI-screened group (2 per 1,000 screenings) than in the MRI–“offered but declined” (7.1 per 1,000 screenings) or mammogram-only groups (6 per 1,000 screenings).
 

How these results influence practice

American physicians are obligated to inform women with dense breast tissue about the limitations (for them) of conventional mammography, an unquantified, but elevated, risk of breast cancer in women with dense breast tissue, and the fact that there are no universally accepted recommended subsequent steps those women should take.

One side benefit of the requirement to disclose information about breast density, however, is that disclosure can prompt discussions about breast cancer risk reduction – an important discussion with multiple possible health-maintaining interventions.

The DENSE trial is very important news, with potential for even more value in future years. It is finite (2 years of study, with only one MRI scan mandated), narrow (Vopara or BI-RADs breast density grade 4 only), and oligo-institutional (eight participating centers in the Netherlands). Still, it provides randomized, rigorously gathered and analyzed data where there were previously none. Importantly, it answers the question, “So what can I do now, doctor?”

I have some concerns about whether we, as a medical community, have the discipline to restrict application of supplemental MRI screening beyond the population that was studied in the Netherlands. Will we be able to restrain ourselves from ordering MRI scans in women with heterogeneously dense – but not extremely dense – breasts? Will we truly manage patients whose MRI scans had BI-RADs readings of less than 4 in the rigorous, but conservative, fashion employed in the trial? Would we miss fewer significant cancers and subject fewer patients to potential expense and harm with annual mammography, instead of the biennial screening performed in the Netherlands? Does tomo-synthesis improve the interpretation of screening mammograms so much that the interval cancer rate is a lot closer to the rate obtained with supplemental MRI scans? Is the expense of MRI scanning, with the resultant subsequent tests and procedures, justified by the reduction in detecting relatively favorable breast cancers that may not materially impact overall survival?

The DENSE study promises to be a “gift that keeps on giving” as the investigators continue to assess a number of factors including: the value of ongoing supplemental MRI scans (compared with the one-time-only screening reported here); whether there will be a reduction in the advanced cancers and subsequent mortality benefit; the extent of over diagnosis, costs, and impact on quality-of-life; and the applicability of artificial intelligence techniques to reduce false positive MRI results.

While the study may not be practice changing in the United States at the present time, it may be just that as subsequent analyses emerge.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight two recent studies that reinforce prior diagnostic and treatment preferences among many oncologists and will certainly influence the discussions we all will have with our patients in the coming weeks and months.

Rituximab maintenance in follicular lymphoma

The largest trial addressing the role of maintenance CD20-targeted antibody therapy was the Primary Rituximab and Maintenance (PRIMA) phase 3, intergroup study in 1,018 advanced follicular lymphoma patients with an initial response to induction chemoimmunotherapy. The induction regimen could be either of three commonly used regimens plus rituximab. Importantly, none of the induction regimens included bendamustine.

Patients were randomized to 2 years of rituximab maintenance or observation. Prior interim analyses at 3 and 6 years showed improvements for the rituximab maintenance patients in progression-free survival and other secondary endpoints, but no improvement in overall survival. Emmanuel Bachy, MD, PhD, and colleagues published the final survival data after 9 years of follow-up, including a final safety analysis (J Clin Oncol. 2019 Nov 1;37[31]:2815-24).

Among the 607 patients consenting to extended follow-up, median progression-free survival was 10.5 years with rituximab maintenance, compared with 4.1 years for observation (hazard ratio, 0.61; P less than .001). There were more patients with progression-free survival at 3 years, complete response or unconfirmed complete response at 2 years, longer time to next antilymphoma treatment, and later time to next chemotherapy. But the 10-year overall survival was similar in the two groups, as were the quality of life ratings.

In all, 503 patients experienced disease progression. Overall survival after progression was shorter in the rituximab maintenance arm versus the observation arm. Among the approximately 4% of patients experiencing transformation from follicular lymphoma to a more aggressive histology, there was no difference observed in time to transformation. Results were independent of the induction regimen received, response to induction, Follicular Lymphoma International Prognostic Index score, and other clinical factors.

In the safety analysis, there were more grade 3-4 adverse events among the rituximab maintenance patients – primarily cytopenia and infections – more serious adverse events, and more adverse events overall. Fatal adverse events were low in both groups (1.6 vs. 0.6%).
 

How these results influence practice

Many years ago, a senior mentor of mine taught that “progression-free survival is an important endpoint since the quality of life for patients is generally superior before relapse than afterwards.”

With that mantra playing in my mind and with the reality that discussions about relapse and subsequent treatment are never easy, the results of PRIMA seem straightforward: Rituximab maintenance is beneficial, despite the absence of an overall survival benefit, in a disease with multiple options for subsequent therapy and a long natural history. In this 9-year, final analysis of PRIMA, rituximab maintenance seems to have achieved its goals of deepening responses with low (but not inconsequential) toxicity and delaying substantially those difficult conversations with patients about how to proceed after relapse.

The influence of the final analysis of PRIMA, however, may be more complicated that it would initially seem. Bendamustine-containing regimens were not employed, are commonly used now, and some studies with bendamustine have suggested higher nonrelapse mortality with rituximab maintenance.

Low-grade adverse events take on greater importance for patients on long-term therapy than they do for patients receiving abbreviated treatment, and with noncurative treatment, the higher adverse event profile with 2 years of rituximab maintenance needs to be taken seriously. Induction and maintenance regimens involving rituximab alone, lenalidomide, or obinutuzumab may be preferred for some patients. For all of those reasons, the discussion about rituximab with advanced follicular lymphoma patients remains a long one, demanding detailed descriptions of risks, benefits, limitations of the data, and multiple modern day alternatives to the treatments employed in PRIMA.
 

Supplemental MRI for dense breast tissue

In the DENSE trial, investigators assigned 40,373 women with extremely dense breast tissue and negative results on screening mammography to be offered either supplemental MRI or mammography screening every other year only. The women were 50-75 years old and were enrolled in the Dutch population-based digital mammography screening program. The primary outcome was the difference in the number of cancers that developed in the 2-year interval between mammograms (N Engl J Med 2019;381:2091-102).

The interval cancer rate was 2.5 per 1,000 screenings among 4,783 women in the “MRI-invitation” group (41% of whom did not actually agree to have an MRI), and 5 per 1,000 in the 32,312 women in the “mammography-only” group, a difference of 2.5 per 1,000 screenings (P less than .001).

Of the 20 interval cancers diagnosed in the MRI-invitation group, 4 were diagnosed in the 59% of women who had undergone MRI (0.8 per 1,000 screenings). The remaining 16 were diagnosed in those who had declined an MRI (4.9 per 1,000 screenings) – virtually identical to the rate of interval cancers in the group that was not invited to have an MRI. This speaks against nonrandom allocation of patients between the mammography-only and the supplemental MRI groups.

Although supplemental MRI was associated with a cancer-detection rate of 16.5 per 1,000 screenings, there was a false positive rate of 8.0% (79.8 per 1,000 screenings). Of the women who underwent a breast biopsy after MRI, 73.7% did not have cancer. Among the women who had MRI-detected cancers, in general, the malignancies diagnosed were smaller, more likely node negative, better differentiated, and more often hormone receptor–positive, compared with those in the mammography-only group.

At the next screening mammogram, the cancer detection rate was lower in the MRI-screened group (2 per 1,000 screenings) than in the MRI–“offered but declined” (7.1 per 1,000 screenings) or mammogram-only groups (6 per 1,000 screenings).
 

How these results influence practice

American physicians are obligated to inform women with dense breast tissue about the limitations (for them) of conventional mammography, an unquantified, but elevated, risk of breast cancer in women with dense breast tissue, and the fact that there are no universally accepted recommended subsequent steps those women should take.

One side benefit of the requirement to disclose information about breast density, however, is that disclosure can prompt discussions about breast cancer risk reduction – an important discussion with multiple possible health-maintaining interventions.

The DENSE trial is very important news, with potential for even more value in future years. It is finite (2 years of study, with only one MRI scan mandated), narrow (Vopara or BI-RADs breast density grade 4 only), and oligo-institutional (eight participating centers in the Netherlands). Still, it provides randomized, rigorously gathered and analyzed data where there were previously none. Importantly, it answers the question, “So what can I do now, doctor?”

I have some concerns about whether we, as a medical community, have the discipline to restrict application of supplemental MRI screening beyond the population that was studied in the Netherlands. Will we be able to restrain ourselves from ordering MRI scans in women with heterogeneously dense – but not extremely dense – breasts? Will we truly manage patients whose MRI scans had BI-RADs readings of less than 4 in the rigorous, but conservative, fashion employed in the trial? Would we miss fewer significant cancers and subject fewer patients to potential expense and harm with annual mammography, instead of the biennial screening performed in the Netherlands? Does tomo-synthesis improve the interpretation of screening mammograms so much that the interval cancer rate is a lot closer to the rate obtained with supplemental MRI scans? Is the expense of MRI scanning, with the resultant subsequent tests and procedures, justified by the reduction in detecting relatively favorable breast cancers that may not materially impact overall survival?

The DENSE study promises to be a “gift that keeps on giving” as the investigators continue to assess a number of factors including: the value of ongoing supplemental MRI scans (compared with the one-time-only screening reported here); whether there will be a reduction in the advanced cancers and subsequent mortality benefit; the extent of over diagnosis, costs, and impact on quality-of-life; and the applicability of artificial intelligence techniques to reduce false positive MRI results.

While the study may not be practice changing in the United States at the present time, it may be just that as subsequent analyses emerge.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight two recent studies that reinforce prior diagnostic and treatment preferences among many oncologists and will certainly influence the discussions we all will have with our patients in the coming weeks and months.

Rituximab maintenance in follicular lymphoma

The largest trial addressing the role of maintenance CD20-targeted antibody therapy was the Primary Rituximab and Maintenance (PRIMA) phase 3, intergroup study in 1,018 advanced follicular lymphoma patients with an initial response to induction chemoimmunotherapy. The induction regimen could be either of three commonly used regimens plus rituximab. Importantly, none of the induction regimens included bendamustine.

Patients were randomized to 2 years of rituximab maintenance or observation. Prior interim analyses at 3 and 6 years showed improvements for the rituximab maintenance patients in progression-free survival and other secondary endpoints, but no improvement in overall survival. Emmanuel Bachy, MD, PhD, and colleagues published the final survival data after 9 years of follow-up, including a final safety analysis (J Clin Oncol. 2019 Nov 1;37[31]:2815-24).

Among the 607 patients consenting to extended follow-up, median progression-free survival was 10.5 years with rituximab maintenance, compared with 4.1 years for observation (hazard ratio, 0.61; P less than .001). There were more patients with progression-free survival at 3 years, complete response or unconfirmed complete response at 2 years, longer time to next antilymphoma treatment, and later time to next chemotherapy. But the 10-year overall survival was similar in the two groups, as were the quality of life ratings.

In all, 503 patients experienced disease progression. Overall survival after progression was shorter in the rituximab maintenance arm versus the observation arm. Among the approximately 4% of patients experiencing transformation from follicular lymphoma to a more aggressive histology, there was no difference observed in time to transformation. Results were independent of the induction regimen received, response to induction, Follicular Lymphoma International Prognostic Index score, and other clinical factors.

In the safety analysis, there were more grade 3-4 adverse events among the rituximab maintenance patients – primarily cytopenia and infections – more serious adverse events, and more adverse events overall. Fatal adverse events were low in both groups (1.6 vs. 0.6%).
 

How these results influence practice

Many years ago, a senior mentor of mine taught that “progression-free survival is an important endpoint since the quality of life for patients is generally superior before relapse than afterwards.”

With that mantra playing in my mind and with the reality that discussions about relapse and subsequent treatment are never easy, the results of PRIMA seem straightforward: Rituximab maintenance is beneficial, despite the absence of an overall survival benefit, in a disease with multiple options for subsequent therapy and a long natural history. In this 9-year, final analysis of PRIMA, rituximab maintenance seems to have achieved its goals of deepening responses with low (but not inconsequential) toxicity and delaying substantially those difficult conversations with patients about how to proceed after relapse.

The influence of the final analysis of PRIMA, however, may be more complicated that it would initially seem. Bendamustine-containing regimens were not employed, are commonly used now, and some studies with bendamustine have suggested higher nonrelapse mortality with rituximab maintenance.

Low-grade adverse events take on greater importance for patients on long-term therapy than they do for patients receiving abbreviated treatment, and with noncurative treatment, the higher adverse event profile with 2 years of rituximab maintenance needs to be taken seriously. Induction and maintenance regimens involving rituximab alone, lenalidomide, or obinutuzumab may be preferred for some patients. For all of those reasons, the discussion about rituximab with advanced follicular lymphoma patients remains a long one, demanding detailed descriptions of risks, benefits, limitations of the data, and multiple modern day alternatives to the treatments employed in PRIMA.
 

Supplemental MRI for dense breast tissue

In the DENSE trial, investigators assigned 40,373 women with extremely dense breast tissue and negative results on screening mammography to be offered either supplemental MRI or mammography screening every other year only. The women were 50-75 years old and were enrolled in the Dutch population-based digital mammography screening program. The primary outcome was the difference in the number of cancers that developed in the 2-year interval between mammograms (N Engl J Med 2019;381:2091-102).

The interval cancer rate was 2.5 per 1,000 screenings among 4,783 women in the “MRI-invitation” group (41% of whom did not actually agree to have an MRI), and 5 per 1,000 in the 32,312 women in the “mammography-only” group, a difference of 2.5 per 1,000 screenings (P less than .001).

Of the 20 interval cancers diagnosed in the MRI-invitation group, 4 were diagnosed in the 59% of women who had undergone MRI (0.8 per 1,000 screenings). The remaining 16 were diagnosed in those who had declined an MRI (4.9 per 1,000 screenings) – virtually identical to the rate of interval cancers in the group that was not invited to have an MRI. This speaks against nonrandom allocation of patients between the mammography-only and the supplemental MRI groups.

Although supplemental MRI was associated with a cancer-detection rate of 16.5 per 1,000 screenings, there was a false positive rate of 8.0% (79.8 per 1,000 screenings). Of the women who underwent a breast biopsy after MRI, 73.7% did not have cancer. Among the women who had MRI-detected cancers, in general, the malignancies diagnosed were smaller, more likely node negative, better differentiated, and more often hormone receptor–positive, compared with those in the mammography-only group.

At the next screening mammogram, the cancer detection rate was lower in the MRI-screened group (2 per 1,000 screenings) than in the MRI–“offered but declined” (7.1 per 1,000 screenings) or mammogram-only groups (6 per 1,000 screenings).
 

How these results influence practice

American physicians are obligated to inform women with dense breast tissue about the limitations (for them) of conventional mammography, an unquantified, but elevated, risk of breast cancer in women with dense breast tissue, and the fact that there are no universally accepted recommended subsequent steps those women should take.

One side benefit of the requirement to disclose information about breast density, however, is that disclosure can prompt discussions about breast cancer risk reduction – an important discussion with multiple possible health-maintaining interventions.

The DENSE trial is very important news, with potential for even more value in future years. It is finite (2 years of study, with only one MRI scan mandated), narrow (Vopara or BI-RADs breast density grade 4 only), and oligo-institutional (eight participating centers in the Netherlands). Still, it provides randomized, rigorously gathered and analyzed data where there were previously none. Importantly, it answers the question, “So what can I do now, doctor?”

I have some concerns about whether we, as a medical community, have the discipline to restrict application of supplemental MRI screening beyond the population that was studied in the Netherlands. Will we be able to restrain ourselves from ordering MRI scans in women with heterogeneously dense – but not extremely dense – breasts? Will we truly manage patients whose MRI scans had BI-RADs readings of less than 4 in the rigorous, but conservative, fashion employed in the trial? Would we miss fewer significant cancers and subject fewer patients to potential expense and harm with annual mammography, instead of the biennial screening performed in the Netherlands? Does tomo-synthesis improve the interpretation of screening mammograms so much that the interval cancer rate is a lot closer to the rate obtained with supplemental MRI scans? Is the expense of MRI scanning, with the resultant subsequent tests and procedures, justified by the reduction in detecting relatively favorable breast cancers that may not materially impact overall survival?

The DENSE study promises to be a “gift that keeps on giving” as the investigators continue to assess a number of factors including: the value of ongoing supplemental MRI scans (compared with the one-time-only screening reported here); whether there will be a reduction in the advanced cancers and subsequent mortality benefit; the extent of over diagnosis, costs, and impact on quality-of-life; and the applicability of artificial intelligence techniques to reduce false positive MRI results.

While the study may not be practice changing in the United States at the present time, it may be just that as subsequent analyses emerge.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

[email protected]

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

[email protected]

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

[email protected]

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.