For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

SAN FRANCISCO – For years, 50 years old has been the age at which screening for colorectal cancer (CRC) began in the United States, but recently, one group lowered the starting age to 45 years.

pixologicstudio/Thinkstock

This move by the American Cancer Society in 2018 was made in reaction to reports of an increase in the incidence of CRC in younger adults.

However, other groups have stayed with the benchmark 50 years. This includes the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network.

Should the age be lowered in view of the mounting reports of an increase in CRC in younger adults? Experts argued both for and against the move here at the 2020 Gastrointestinal Cancers Symposium.

“We’re having this debate because the health of more than 20 million Americans is in the balance,” commented David Weinberg, MD, MSc, chairman of the department of medicine at Fox Chase Cancer Center in Philadelphia. “This is not just an academic discussion.” If the screening age shifts to 5 years earlier, the impact nationally would be about 30,000 colorectal cancers and 11,000 deaths averted.

“It will take about 11 million additional colonoscopies ... and the overall bill would be $10 billion. That’s not a small number, but if the country has the resources and we want to do this, I would say we can,” argued Uri Ladabaum, MD, director of the gastrointestinal cancer prevention program and the clinical chief of the division of gastroenterology and hepatology at Stanford (Calif.) University.

Lower the age

Dr. Ladabaum argued in favor of lowering the age to 45 years to start screening. “In life, 60 may be the new 40, but for colorectal cancer screening, 45 is definitely the new 50,” he said. Anticipating arguments against such a move, he focused on several points.

First, the magnitude of the problem is certainly not small, he noted, pointing to a 2017 study showing that colorectal cancer rates have increased by 1%-2.4% annually since the mid-1980s in persons aged 20-39 years and by 0.5%-1.3% since the mid-1990s in adults aged 40-54 years (J Natl Cancer Inst. 2017;109:djw322). Rectal cancer incidence has been increasing even more rapidly, at a rate of about 3.2% annually during 1974-2013 in adults aged 20-29 years.

Overall, people who were born around 1990 and later have double the risk of colon cancer (incidence rate ratio, 2.40) and quadruple the risk of rectal cancer (IRR, 4.32) as compared with those born circa 1950.

“Thus, 45- to 49-year-olds are beginning to look like yesterday’s 50- to 54-year-olds used to be,” said Dr. Ladabaum.

One issue that has been raised is lead-time bias, with the burning question: Are the cancers found in adults in their 40s simply the same ones that would have eventually been detected in their 50s? Dr. Ladabaum argued that they are not, referencing a 2019 study showing that among persons aged 40 through 49 years, the disease was diagnosed at later stages (JAMA. 2019;321:1933-4).

For those aged 40- 49 years, there was a significant increase in incidence during 1995-2015. The proportion of distant cancers increased significantly (from 21.7% to 26.6%; P less than .001), and the authors of the study had noted that this increase of 4.9% could not be explained by a decrease in unstaged cases. “In the early ’90s and mid-’90s, we began to see an increase in all stages,” Dr. Ladabaum noted. “And the most important thing here is the distant cancers over time. They’ve gone up.” If the only explanation was lead time bias in people aged 40- 49 years, then a person screened and diagnosed with cancer at age 48 would have earlier-stage disease than if it had been found at age 51. “So is this all lead-time bias?” he said. “I think the answer is no.”

Next, Dr. Ladabaum tackled the issue of whether benefit/risk ratio of CRC screening is different among younger vs. older adults. This is difficult to tease out, he suggested, as the data are sparse and there were no controlled studies to date to address that. One study from Taiwan, which looked at the outcomes of fecal immunochemical testing (FIT), showed that in different age groups, the hazard ratio for detecting cancer in those with positive results is higher in younger people vs. older ones (J Clin Gastroenterol. 2016 Oct;50[9]:761-8).

“Indirect evidence shows that if we do a FIT test and it’s positive, it probably means something,” he said. “But is there something magical that at age 50 and older – that it becomes a screenable disease, and through age 49 it’s not screenable? I would say no. Biology is not like this.”

Finally, is it cost effective to start earlier? In a modeling projection published last summer by Dr. Ladabaum and colleagues, starting at 45 years would avert about four colorectal cancers and two colorectal cancer deaths per 1,000 people, and the cohort would gain approximately 14 quality-adjusted life years (Gastroenterology. 2019;157:137-48).

“The incremental cost per quality-adjusted life year gained is highly acceptable,” said Dr. Ladabaum. “This is well within the range of what’s considered cost-effective in the United States – under $35,000 for colonoscopy, and under $8,000 for fecal immunochemical tests.”

Therefore, the answer is yes, it is cost effective, he concluded.

Not so fast ...

Arguing the case against a lowering of the starting age, Dr. Weinberg agreed with Dr. Ladabaum that colon cancer risk for younger people is rising.

That risk has increased from 5.9/100,000 to 7.2/100,000, which is a relative increase of 22%, he noted.

“That is what newspapers will want to put on their headlines to sensationalize it – that the risk of colon cancer for young people is up by over 20%,” said Dr. Weinberg. “But that represents an absolute risk of just 1.3 more people/100,000. Put in some context, 99.9% of people in their 40s will not develop colon cancer.”

This observation was not to “make light of the remainder,” he emphasized, but “the overwhelming majority are not going to get this disease at this age,” he noted.

“It’s also not entirely clear that starting screening at 45 is the right answer,” he added.

“Taken to a somewhat ridiculous extreme,” he continued, “why not start at 40? You’ll catch more people that way, but no one is advocating that.”

A better understanding of the factors contributing to the increased CRC incidence seen in younger adults is very important, he argued, and he suggested that some of it may occur because of screening, along with factors such as obesity, diabetes, and childhood exposures.

Modeling has been done to calculate the risk and benefit of early screening, but while useful for decision making, models are “usually wrong and sit near the bottom of the evidence hierarchy.”

“Models help inform decisions, but they don’t define the standard of care,” Dr. Weinberg said. “No one would vaccinate a population based on a model.”

Dr. Weinberg also emphasized that the new recommendation from the American Cancer Society to start screening at age 45 years is qualified. This means that while “clear evidence of benefit exists,” so does uncertainty about whether “the benefits really outweigh the harms.”

The current evidence for reducing the screening age is not yet clear, he believes, and he questioned the premise that age should be the only criteria for cancer stratification.

Dr. Weinberg cited one study that looked at early-onset colon cancer (ages 18-49 years) and compared it with two groups: patients diagnosed at 50 years and older and matched controls (Clin Gastroenterol Hepatol. 2019;S1542-3565[19]31108-5). Besides age, the study authors identified several nonmodifiable risk factors that were associated with early-onset disease, including sex, race, history of inflammatory bowel disease (IBD), and family history of colorectal cancer.

“Being male was a risk factor and having a family history increased your risk by three times,” said Dr. Weinberg. “And I would note that this study had removed people, at least as best one can, who were known to have syndromic risks of early-onset colon cancer (such as familial adenomatous polyposis.”

Earlier screening (by age 40 years) should already be taking place in people with such syndromes, he commented, as well as those with a known family history and IBD. “Those recommendations were there before the ACS, and we don’t necessarily need another one,” he added.

To make things a little more confusing, a second recent study, using National Cancer Data Base data from 2004 to 2015, identified another set of factors associated with colon cancer in younger adults (Cancer. 2019 Nov 1;125:3828-35). This study showed diagnosis younger than 50 years rose only in non-Hispanic white men, in Hispanic and non-Hispanic white women, and in those living in urban vs. rural areas.

“But it gets more interesting,” Dr. Weinberg pointed out. “Risk increased over time for people in the highest zip code income quartile and those with private insurance, and risk was lower for people with Medicaid and no insurance at all,” he noted. “Well, that smacks of access to me,” he commented.

Another issue is the possibility of lead-time bias. During 1975-2015, incidence rose over time, according to Surveillance, Epidemiology, and End Results data (J Natl Cancer Inst. 2017 Aug;109:djw322). Screening of persons younger than age 49 years also more than doubled, from a low level in 2000 of about 6% to more than 15% by 2010. As screening increases, the incidence increases, Dr. Weinberg pointed out. “But mortality doesn’t change. And despite what Dr. Ladabaum said a moment ago about lead-time bias, that is textbook lead-time bias in any epidemiology study.”

Finally, it is essential to carefully weigh the benefit against the risk, Dr. Weinberg said.

A core principle of population screening is to create more future health benefits than harms, and if the screening age is lowered, several million additional colonoscopies will be performed.

Colonoscopy reduces the colorectal cancer mortality risk by about 75%, and the incidence of the disease is 7.2/100,000 in the younger age group. But colonoscopy-specific mortality – just having the test – is associated with a death rate of 7/100,000,” Dr. Weinberg pointed out. “Let’s not forget that there is a risk associated with this procedure.” (Gastrointest Endosc. 2011 Oct;74:745-52).

Dr. Weinberg emphasized that everyone wants to reduce the burden of cancer, and models are helpful for that purpose. “They’re obviously thought provoking, but they’re not adequate to drive change without additional evidence of clinical and cost-effectiveness,” he said. “These are important questions that need better data.”

He added that without changing the current screening protocol, “we could certainly emphasize more than ever the impact of family history and IBD on colon cancer risk and colon cancer prevention.”

“And certainly, there’s plenty of evidence that patients with a known family history of colon cancer are not getting screened at the right age or with the right frequency,” Dr. Weinberg concluded. “We can do better. All of us can do better.”

Dr. Weinberg has disclosed relationships with Fujifilm and Exact Sciences. Dr. Ladabaum has disclosed relationships with Lean Medical, Universal Dx, Clinical Genomics, Medtronic, Modus GI, and Quorum Consulting.
 

This article first appeared on Medscape.com.

SAN FRANCISCO – For years, 50 years old has been the age at which screening for colorectal cancer (CRC) began in the United States, but recently, one group lowered the starting age to 45 years.

pixologicstudio/Thinkstock

This move by the American Cancer Society in 2018 was made in reaction to reports of an increase in the incidence of CRC in younger adults.

However, other groups have stayed with the benchmark 50 years. This includes the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network.

Should the age be lowered in view of the mounting reports of an increase in CRC in younger adults? Experts argued both for and against the move here at the 2020 Gastrointestinal Cancers Symposium.

“We’re having this debate because the health of more than 20 million Americans is in the balance,” commented David Weinberg, MD, MSc, chairman of the department of medicine at Fox Chase Cancer Center in Philadelphia. “This is not just an academic discussion.” If the screening age shifts to 5 years earlier, the impact nationally would be about 30,000 colorectal cancers and 11,000 deaths averted.

“It will take about 11 million additional colonoscopies ... and the overall bill would be $10 billion. That’s not a small number, but if the country has the resources and we want to do this, I would say we can,” argued Uri Ladabaum, MD, director of the gastrointestinal cancer prevention program and the clinical chief of the division of gastroenterology and hepatology at Stanford (Calif.) University.

Lower the age

Dr. Ladabaum argued in favor of lowering the age to 45 years to start screening. “In life, 60 may be the new 40, but for colorectal cancer screening, 45 is definitely the new 50,” he said. Anticipating arguments against such a move, he focused on several points.

First, the magnitude of the problem is certainly not small, he noted, pointing to a 2017 study showing that colorectal cancer rates have increased by 1%-2.4% annually since the mid-1980s in persons aged 20-39 years and by 0.5%-1.3% since the mid-1990s in adults aged 40-54 years (J Natl Cancer Inst. 2017;109:djw322). Rectal cancer incidence has been increasing even more rapidly, at a rate of about 3.2% annually during 1974-2013 in adults aged 20-29 years.

Overall, people who were born around 1990 and later have double the risk of colon cancer (incidence rate ratio, 2.40) and quadruple the risk of rectal cancer (IRR, 4.32) as compared with those born circa 1950.

“Thus, 45- to 49-year-olds are beginning to look like yesterday’s 50- to 54-year-olds used to be,” said Dr. Ladabaum.

One issue that has been raised is lead-time bias, with the burning question: Are the cancers found in adults in their 40s simply the same ones that would have eventually been detected in their 50s? Dr. Ladabaum argued that they are not, referencing a 2019 study showing that among persons aged 40 through 49 years, the disease was diagnosed at later stages (JAMA. 2019;321:1933-4).

For those aged 40- 49 years, there was a significant increase in incidence during 1995-2015. The proportion of distant cancers increased significantly (from 21.7% to 26.6%; P less than .001), and the authors of the study had noted that this increase of 4.9% could not be explained by a decrease in unstaged cases. “In the early ’90s and mid-’90s, we began to see an increase in all stages,” Dr. Ladabaum noted. “And the most important thing here is the distant cancers over time. They’ve gone up.” If the only explanation was lead time bias in people aged 40- 49 years, then a person screened and diagnosed with cancer at age 48 would have earlier-stage disease than if it had been found at age 51. “So is this all lead-time bias?” he said. “I think the answer is no.”

Next, Dr. Ladabaum tackled the issue of whether benefit/risk ratio of CRC screening is different among younger vs. older adults. This is difficult to tease out, he suggested, as the data are sparse and there were no controlled studies to date to address that. One study from Taiwan, which looked at the outcomes of fecal immunochemical testing (FIT), showed that in different age groups, the hazard ratio for detecting cancer in those with positive results is higher in younger people vs. older ones (J Clin Gastroenterol. 2016 Oct;50[9]:761-8).

“Indirect evidence shows that if we do a FIT test and it’s positive, it probably means something,” he said. “But is there something magical that at age 50 and older – that it becomes a screenable disease, and through age 49 it’s not screenable? I would say no. Biology is not like this.”

Finally, is it cost effective to start earlier? In a modeling projection published last summer by Dr. Ladabaum and colleagues, starting at 45 years would avert about four colorectal cancers and two colorectal cancer deaths per 1,000 people, and the cohort would gain approximately 14 quality-adjusted life years (Gastroenterology. 2019;157:137-48).

“The incremental cost per quality-adjusted life year gained is highly acceptable,” said Dr. Ladabaum. “This is well within the range of what’s considered cost-effective in the United States – under $35,000 for colonoscopy, and under $8,000 for fecal immunochemical tests.”

Therefore, the answer is yes, it is cost effective, he concluded.

Not so fast ...

Arguing the case against a lowering of the starting age, Dr. Weinberg agreed with Dr. Ladabaum that colon cancer risk for younger people is rising.

That risk has increased from 5.9/100,000 to 7.2/100,000, which is a relative increase of 22%, he noted.

“That is what newspapers will want to put on their headlines to sensationalize it – that the risk of colon cancer for young people is up by over 20%,” said Dr. Weinberg. “But that represents an absolute risk of just 1.3 more people/100,000. Put in some context, 99.9% of people in their 40s will not develop colon cancer.”

This observation was not to “make light of the remainder,” he emphasized, but “the overwhelming majority are not going to get this disease at this age,” he noted.

“It’s also not entirely clear that starting screening at 45 is the right answer,” he added.

“Taken to a somewhat ridiculous extreme,” he continued, “why not start at 40? You’ll catch more people that way, but no one is advocating that.”

A better understanding of the factors contributing to the increased CRC incidence seen in younger adults is very important, he argued, and he suggested that some of it may occur because of screening, along with factors such as obesity, diabetes, and childhood exposures.

Modeling has been done to calculate the risk and benefit of early screening, but while useful for decision making, models are “usually wrong and sit near the bottom of the evidence hierarchy.”

“Models help inform decisions, but they don’t define the standard of care,” Dr. Weinberg said. “No one would vaccinate a population based on a model.”

Dr. Weinberg also emphasized that the new recommendation from the American Cancer Society to start screening at age 45 years is qualified. This means that while “clear evidence of benefit exists,” so does uncertainty about whether “the benefits really outweigh the harms.”

The current evidence for reducing the screening age is not yet clear, he believes, and he questioned the premise that age should be the only criteria for cancer stratification.

Dr. Weinberg cited one study that looked at early-onset colon cancer (ages 18-49 years) and compared it with two groups: patients diagnosed at 50 years and older and matched controls (Clin Gastroenterol Hepatol. 2019;S1542-3565[19]31108-5). Besides age, the study authors identified several nonmodifiable risk factors that were associated with early-onset disease, including sex, race, history of inflammatory bowel disease (IBD), and family history of colorectal cancer.

“Being male was a risk factor and having a family history increased your risk by three times,” said Dr. Weinberg. “And I would note that this study had removed people, at least as best one can, who were known to have syndromic risks of early-onset colon cancer (such as familial adenomatous polyposis.”

Earlier screening (by age 40 years) should already be taking place in people with such syndromes, he commented, as well as those with a known family history and IBD. “Those recommendations were there before the ACS, and we don’t necessarily need another one,” he added.

To make things a little more confusing, a second recent study, using National Cancer Data Base data from 2004 to 2015, identified another set of factors associated with colon cancer in younger adults (Cancer. 2019 Nov 1;125:3828-35). This study showed diagnosis younger than 50 years rose only in non-Hispanic white men, in Hispanic and non-Hispanic white women, and in those living in urban vs. rural areas.

“But it gets more interesting,” Dr. Weinberg pointed out. “Risk increased over time for people in the highest zip code income quartile and those with private insurance, and risk was lower for people with Medicaid and no insurance at all,” he noted. “Well, that smacks of access to me,” he commented.

Another issue is the possibility of lead-time bias. During 1975-2015, incidence rose over time, according to Surveillance, Epidemiology, and End Results data (J Natl Cancer Inst. 2017 Aug;109:djw322). Screening of persons younger than age 49 years also more than doubled, from a low level in 2000 of about 6% to more than 15% by 2010. As screening increases, the incidence increases, Dr. Weinberg pointed out. “But mortality doesn’t change. And despite what Dr. Ladabaum said a moment ago about lead-time bias, that is textbook lead-time bias in any epidemiology study.”

Finally, it is essential to carefully weigh the benefit against the risk, Dr. Weinberg said.

A core principle of population screening is to create more future health benefits than harms, and if the screening age is lowered, several million additional colonoscopies will be performed.

Colonoscopy reduces the colorectal cancer mortality risk by about 75%, and the incidence of the disease is 7.2/100,000 in the younger age group. But colonoscopy-specific mortality – just having the test – is associated with a death rate of 7/100,000,” Dr. Weinberg pointed out. “Let’s not forget that there is a risk associated with this procedure.” (Gastrointest Endosc. 2011 Oct;74:745-52).

Dr. Weinberg emphasized that everyone wants to reduce the burden of cancer, and models are helpful for that purpose. “They’re obviously thought provoking, but they’re not adequate to drive change without additional evidence of clinical and cost-effectiveness,” he said. “These are important questions that need better data.”

He added that without changing the current screening protocol, “we could certainly emphasize more than ever the impact of family history and IBD on colon cancer risk and colon cancer prevention.”

“And certainly, there’s plenty of evidence that patients with a known family history of colon cancer are not getting screened at the right age or with the right frequency,” Dr. Weinberg concluded. “We can do better. All of us can do better.”

Dr. Weinberg has disclosed relationships with Fujifilm and Exact Sciences. Dr. Ladabaum has disclosed relationships with Lean Medical, Universal Dx, Clinical Genomics, Medtronic, Modus GI, and Quorum Consulting.
 

This article first appeared on Medscape.com.

SAN FRANCISCO – For years, 50 years old has been the age at which screening for colorectal cancer (CRC) began in the United States, but recently, one group lowered the starting age to 45 years.

pixologicstudio/Thinkstock

This move by the American Cancer Society in 2018 was made in reaction to reports of an increase in the incidence of CRC in younger adults.

However, other groups have stayed with the benchmark 50 years. This includes the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network.

Should the age be lowered in view of the mounting reports of an increase in CRC in younger adults? Experts argued both for and against the move here at the 2020 Gastrointestinal Cancers Symposium.

“We’re having this debate because the health of more than 20 million Americans is in the balance,” commented David Weinberg, MD, MSc, chairman of the department of medicine at Fox Chase Cancer Center in Philadelphia. “This is not just an academic discussion.” If the screening age shifts to 5 years earlier, the impact nationally would be about 30,000 colorectal cancers and 11,000 deaths averted.

“It will take about 11 million additional colonoscopies ... and the overall bill would be $10 billion. That’s not a small number, but if the country has the resources and we want to do this, I would say we can,” argued Uri Ladabaum, MD, director of the gastrointestinal cancer prevention program and the clinical chief of the division of gastroenterology and hepatology at Stanford (Calif.) University.

Lower the age

Dr. Ladabaum argued in favor of lowering the age to 45 years to start screening. “In life, 60 may be the new 40, but for colorectal cancer screening, 45 is definitely the new 50,” he said. Anticipating arguments against such a move, he focused on several points.

First, the magnitude of the problem is certainly not small, he noted, pointing to a 2017 study showing that colorectal cancer rates have increased by 1%-2.4% annually since the mid-1980s in persons aged 20-39 years and by 0.5%-1.3% since the mid-1990s in adults aged 40-54 years (J Natl Cancer Inst. 2017;109:djw322). Rectal cancer incidence has been increasing even more rapidly, at a rate of about 3.2% annually during 1974-2013 in adults aged 20-29 years.

Overall, people who were born around 1990 and later have double the risk of colon cancer (incidence rate ratio, 2.40) and quadruple the risk of rectal cancer (IRR, 4.32) as compared with those born circa 1950.

“Thus, 45- to 49-year-olds are beginning to look like yesterday’s 50- to 54-year-olds used to be,” said Dr. Ladabaum.

One issue that has been raised is lead-time bias, with the burning question: Are the cancers found in adults in their 40s simply the same ones that would have eventually been detected in their 50s? Dr. Ladabaum argued that they are not, referencing a 2019 study showing that among persons aged 40 through 49 years, the disease was diagnosed at later stages (JAMA. 2019;321:1933-4).

For those aged 40- 49 years, there was a significant increase in incidence during 1995-2015. The proportion of distant cancers increased significantly (from 21.7% to 26.6%; P less than .001), and the authors of the study had noted that this increase of 4.9% could not be explained by a decrease in unstaged cases. “In the early ’90s and mid-’90s, we began to see an increase in all stages,” Dr. Ladabaum noted. “And the most important thing here is the distant cancers over time. They’ve gone up.” If the only explanation was lead time bias in people aged 40- 49 years, then a person screened and diagnosed with cancer at age 48 would have earlier-stage disease than if it had been found at age 51. “So is this all lead-time bias?” he said. “I think the answer is no.”

Next, Dr. Ladabaum tackled the issue of whether benefit/risk ratio of CRC screening is different among younger vs. older adults. This is difficult to tease out, he suggested, as the data are sparse and there were no controlled studies to date to address that. One study from Taiwan, which looked at the outcomes of fecal immunochemical testing (FIT), showed that in different age groups, the hazard ratio for detecting cancer in those with positive results is higher in younger people vs. older ones (J Clin Gastroenterol. 2016 Oct;50[9]:761-8).

“Indirect evidence shows that if we do a FIT test and it’s positive, it probably means something,” he said. “But is there something magical that at age 50 and older – that it becomes a screenable disease, and through age 49 it’s not screenable? I would say no. Biology is not like this.”

Finally, is it cost effective to start earlier? In a modeling projection published last summer by Dr. Ladabaum and colleagues, starting at 45 years would avert about four colorectal cancers and two colorectal cancer deaths per 1,000 people, and the cohort would gain approximately 14 quality-adjusted life years (Gastroenterology. 2019;157:137-48).

“The incremental cost per quality-adjusted life year gained is highly acceptable,” said Dr. Ladabaum. “This is well within the range of what’s considered cost-effective in the United States – under $35,000 for colonoscopy, and under $8,000 for fecal immunochemical tests.”

Therefore, the answer is yes, it is cost effective, he concluded.

Not so fast ...

Arguing the case against a lowering of the starting age, Dr. Weinberg agreed with Dr. Ladabaum that colon cancer risk for younger people is rising.

That risk has increased from 5.9/100,000 to 7.2/100,000, which is a relative increase of 22%, he noted.

“That is what newspapers will want to put on their headlines to sensationalize it – that the risk of colon cancer for young people is up by over 20%,” said Dr. Weinberg. “But that represents an absolute risk of just 1.3 more people/100,000. Put in some context, 99.9% of people in their 40s will not develop colon cancer.”

This observation was not to “make light of the remainder,” he emphasized, but “the overwhelming majority are not going to get this disease at this age,” he noted.

“It’s also not entirely clear that starting screening at 45 is the right answer,” he added.

“Taken to a somewhat ridiculous extreme,” he continued, “why not start at 40? You’ll catch more people that way, but no one is advocating that.”

A better understanding of the factors contributing to the increased CRC incidence seen in younger adults is very important, he argued, and he suggested that some of it may occur because of screening, along with factors such as obesity, diabetes, and childhood exposures.

Modeling has been done to calculate the risk and benefit of early screening, but while useful for decision making, models are “usually wrong and sit near the bottom of the evidence hierarchy.”

“Models help inform decisions, but they don’t define the standard of care,” Dr. Weinberg said. “No one would vaccinate a population based on a model.”

Dr. Weinberg also emphasized that the new recommendation from the American Cancer Society to start screening at age 45 years is qualified. This means that while “clear evidence of benefit exists,” so does uncertainty about whether “the benefits really outweigh the harms.”

The current evidence for reducing the screening age is not yet clear, he believes, and he questioned the premise that age should be the only criteria for cancer stratification.

Dr. Weinberg cited one study that looked at early-onset colon cancer (ages 18-49 years) and compared it with two groups: patients diagnosed at 50 years and older and matched controls (Clin Gastroenterol Hepatol. 2019;S1542-3565[19]31108-5). Besides age, the study authors identified several nonmodifiable risk factors that were associated with early-onset disease, including sex, race, history of inflammatory bowel disease (IBD), and family history of colorectal cancer.

“Being male was a risk factor and having a family history increased your risk by three times,” said Dr. Weinberg. “And I would note that this study had removed people, at least as best one can, who were known to have syndromic risks of early-onset colon cancer (such as familial adenomatous polyposis.”

Earlier screening (by age 40 years) should already be taking place in people with such syndromes, he commented, as well as those with a known family history and IBD. “Those recommendations were there before the ACS, and we don’t necessarily need another one,” he added.

To make things a little more confusing, a second recent study, using National Cancer Data Base data from 2004 to 2015, identified another set of factors associated with colon cancer in younger adults (Cancer. 2019 Nov 1;125:3828-35). This study showed diagnosis younger than 50 years rose only in non-Hispanic white men, in Hispanic and non-Hispanic white women, and in those living in urban vs. rural areas.

“But it gets more interesting,” Dr. Weinberg pointed out. “Risk increased over time for people in the highest zip code income quartile and those with private insurance, and risk was lower for people with Medicaid and no insurance at all,” he noted. “Well, that smacks of access to me,” he commented.

Another issue is the possibility of lead-time bias. During 1975-2015, incidence rose over time, according to Surveillance, Epidemiology, and End Results data (J Natl Cancer Inst. 2017 Aug;109:djw322). Screening of persons younger than age 49 years also more than doubled, from a low level in 2000 of about 6% to more than 15% by 2010. As screening increases, the incidence increases, Dr. Weinberg pointed out. “But mortality doesn’t change. And despite what Dr. Ladabaum said a moment ago about lead-time bias, that is textbook lead-time bias in any epidemiology study.”

Finally, it is essential to carefully weigh the benefit against the risk, Dr. Weinberg said.

A core principle of population screening is to create more future health benefits than harms, and if the screening age is lowered, several million additional colonoscopies will be performed.

Colonoscopy reduces the colorectal cancer mortality risk by about 75%, and the incidence of the disease is 7.2/100,000 in the younger age group. But colonoscopy-specific mortality – just having the test – is associated with a death rate of 7/100,000,” Dr. Weinberg pointed out. “Let’s not forget that there is a risk associated with this procedure.” (Gastrointest Endosc. 2011 Oct;74:745-52).

Dr. Weinberg emphasized that everyone wants to reduce the burden of cancer, and models are helpful for that purpose. “They’re obviously thought provoking, but they’re not adequate to drive change without additional evidence of clinical and cost-effectiveness,” he said. “These are important questions that need better data.”

He added that without changing the current screening protocol, “we could certainly emphasize more than ever the impact of family history and IBD on colon cancer risk and colon cancer prevention.”

“And certainly, there’s plenty of evidence that patients with a known family history of colon cancer are not getting screened at the right age or with the right frequency,” Dr. Weinberg concluded. “We can do better. All of us can do better.”

Dr. Weinberg has disclosed relationships with Fujifilm and Exact Sciences. Dr. Ladabaum has disclosed relationships with Lean Medical, Universal Dx, Clinical Genomics, Medtronic, Modus GI, and Quorum Consulting.
 

This article first appeared on Medscape.com.

To the Editor:

Kaposi sarcoma (KS) is a lymphatic endothelial cell neoplasm that frequently presents as multiple vascular cutaneous and mucosal nodules.¹ The classic KS variant typically is described as the presentation of KS in otherwise healthy elderly men of Jewish or Mediterranean descent.² We present 2 cases of classic KS presenting in Mexican women living in Los Angeles County, California, with atypical clinical features.

A 65-year-old woman of Mexican descent presented to the dermatology clinic for evaluation of an asymptomatic growth on the right ventral forearm of 4 months’ duration. Biopsy of the lesion demonstrated a spindle cell proliferation suspicious for KS. Physical examination several months following the initial biopsy revealed a mildly indurated scar on the right ventral forearm with an adjacent faintly erythematous papule (Figure 1A). Repeat biopsy revealed a dermal spindle cell proliferation suggestive of KS (Figures 1B and 1C). S-100 and cytokeratin stains were negative, but a latent nuclear antigen 1 stain for human herpesvirus 8 was positive. Human immunodeficiency virus screening also was negative. Given the isolated findings, the oncology service determined that observation alone was the most appropriate management. Over time, the patient developed several similar scattered erythematous papules, and treatment with imiquimod cream 5% was initiated for 1 month without improvement. She was subsequently given a trial of alitretinoin ointment 0.1% twice daily. The lesions improved, and she continues to be well controlled on this topical therapy alone.

Our 2 cases of classic KS from Los Angeles County had several notable features. Both patients were women from Mexico, a demographic not previously associated with classic KS,⁸ and they did not have risk factors commonly associated with classic KS. We emphasize that classic KS likely is underreported and understudied in the Mexican and South American populations with need for further epidemiological and clinical analyses.

To the Editor:

Kaposi sarcoma (KS) is a lymphatic endothelial cell neoplasm that frequently presents as multiple vascular cutaneous and mucosal nodules.¹ The classic KS variant typically is described as the presentation of KS in otherwise healthy elderly men of Jewish or Mediterranean descent.² We present 2 cases of classic KS presenting in Mexican women living in Los Angeles County, California, with atypical clinical features.

A 65-year-old woman of Mexican descent presented to the dermatology clinic for evaluation of an asymptomatic growth on the right ventral forearm of 4 months’ duration. Biopsy of the lesion demonstrated a spindle cell proliferation suspicious for KS. Physical examination several months following the initial biopsy revealed a mildly indurated scar on the right ventral forearm with an adjacent faintly erythematous papule (Figure 1A). Repeat biopsy revealed a dermal spindle cell proliferation suggestive of KS (Figures 1B and 1C). S-100 and cytokeratin stains were negative, but a latent nuclear antigen 1 stain for human herpesvirus 8 was positive. Human immunodeficiency virus screening also was negative. Given the isolated findings, the oncology service determined that observation alone was the most appropriate management. Over time, the patient developed several similar scattered erythematous papules, and treatment with imiquimod cream 5% was initiated for 1 month without improvement. She was subsequently given a trial of alitretinoin ointment 0.1% twice daily. The lesions improved, and she continues to be well controlled on this topical therapy alone.

Our 2 cases of classic KS from Los Angeles County had several notable features. Both patients were women from Mexico, a demographic not previously associated with classic KS,⁸ and they did not have risk factors commonly associated with classic KS. We emphasize that classic KS likely is underreported and understudied in the Mexican and South American populations with need for further epidemiological and clinical analyses.

To the Editor:

Kaposi sarcoma (KS) is a lymphatic endothelial cell neoplasm that frequently presents as multiple vascular cutaneous and mucosal nodules.¹ The classic KS variant typically is described as the presentation of KS in otherwise healthy elderly men of Jewish or Mediterranean descent.² We present 2 cases of classic KS presenting in Mexican women living in Los Angeles County, California, with atypical clinical features.

A 65-year-old woman of Mexican descent presented to the dermatology clinic for evaluation of an asymptomatic growth on the right ventral forearm of 4 months’ duration. Biopsy of the lesion demonstrated a spindle cell proliferation suspicious for KS. Physical examination several months following the initial biopsy revealed a mildly indurated scar on the right ventral forearm with an adjacent faintly erythematous papule (Figure 1A). Repeat biopsy revealed a dermal spindle cell proliferation suggestive of KS (Figures 1B and 1C). S-100 and cytokeratin stains were negative, but a latent nuclear antigen 1 stain for human herpesvirus 8 was positive. Human immunodeficiency virus screening also was negative. Given the isolated findings, the oncology service determined that observation alone was the most appropriate management. Over time, the patient developed several similar scattered erythematous papules, and treatment with imiquimod cream 5% was initiated for 1 month without improvement. She was subsequently given a trial of alitretinoin ointment 0.1% twice daily. The lesions improved, and she continues to be well controlled on this topical therapy alone.

Our 2 cases of classic KS from Los Angeles County had several notable features. Both patients were women from Mexico, a demographic not previously associated with classic KS,⁸ and they did not have risk factors commonly associated with classic KS. We emphasize that classic KS likely is underreported and understudied in the Mexican and South American populations with need for further epidemiological and clinical analyses.

“I’ve given up, doctor. We gave it our best, but I am at the point where I want to end my life.” You receive this call at 2 a.m., and you’re flooded with a series of emotions and are bewildered – until your training kicks in.

Countless hours of working with patients in emergency department settings while on call as a resident inform your ability to triage the situation. Years of supervision guide your supportive statements as you work collaboratively with your patient to address the emotional and existential distress. As the call proceeds and you realize that your patient will require hospitalization, you are struck by a sobering question: “How am I going to arrange for my patient to go to the nearest hospital in the middle of the night?”

The options for transporting patients with serious mental illness (SMI) typically vary from bad to worse and usually filter down to three possibilities:

1. Get a friend or family member to transport them to the nearest ED.

2. Call emergency medical services (EMS) for transport to the nearest ED.

3. Call the police and request transport to the nearest ED.

Several factors would determine which of those options you would use alone or in combination. Current training paradigms for mental health professionals offer a limited body of literature on evidenced-based strategies for patients with SMI. Transporting high-risk psychiatric patients requires great care and respect, and in-depth knowledge about patients’ vulnerabilities. At best – if not handled properly – these experiences can aggravate patients’ mental health conditions. At worst, they can lead to the loss of our patients. Together, we have more than 40 years’ experience working in complex mental health care systems that run the gamut, from providing direct clinical care to directing mental health care divisions.

Sobering statistics prevail

In 2017, suicide was the 10th leading cause of death in the United States, accounting for more than 47,000 deaths. Suicide was the second-leading cause of death among individuals aged 10-34 and the fourth leading cause of death for individuals aged 35- 54.¹ In 2017, more than 70,200 Americans died from a drug overdose, including illicit drugs and prescription opioids.² Drug overdose deaths nearly quadrupled between 1999 and 2017, from 16,849 deaths to 70,237, respectively.²

The life expectancy of an American with SMI is 14-32 years less than that of the average population.³ Those numbers are on par with many sub-Saharan countries, including Sudan and Ethiopia, and surpass the health disparities for most racial and ethnic groups.

The decrease in life expectancy for people with SMI is rarely the result of suicide but rather the effect of medical comorbidities, including heart disease, stroke, pulmonary disease, diabetes, and cancer.³ Individuals with SMI are much more likely to suffer from chronic illnesses that are associated with co-occurring addictions, side effects of psychotropic medications, and social determinants of mental health, such as poverty.

Major depressive disorder among people with SMI presents acute and chronic medical risks. For example, people with major depressive disorder are at a higher risk for stroke and cardiovascular disease.⁴ There is a threefold increase in cardiac-related deaths for individuals who experience depression after a heart attack.⁵ In addition, depression increases the risk of cardiac-related death after a heart attack more than any other risk factor, except for congestive heart failure.⁶

The transportation challenge

When the complexity of psychiatric conditions is conceptualized to include decreased life expectancy because of medical comorbidities, medical complications that can result from psychotropic medications, and the high incidence of co-occurring substance use disorders (SUDs), it is clear why we are concerned about the type of transport used for patients experiencing a psychiatric emergency.

A common practice for patients presenting for medical treatment for a mental health condition is for them to be transported by law enforcement in handcuffs, or by private vehicle, because of a lack of medical transport options.

One tragic example occurred on Sept. 18, 2018, when two Horry County, S.C., deputies were providing a hospital-to-hospital transport for two mental health patients. The patients, who had no legal charges and were not under arrest, were locked in a transport cage in the back of a law enforcement vehicle for transport during Hurricane Florence. While the driver tried to move through floodwaters, the car stalled and became submerged. The patients were unable to open the locked cage door, and the deputies responsible for the transport did not have a key to unlock the cage.

The two women died as a result of the incident. Both deputies are facing two counts of involuntary manslaughter – with a potential prison sentence of 5 years each.⁷

The system that promotes the use of law enforcement to transport medical patients who are not in legal custody perpetuates a high risk to patients. Also at risk are law enforcement professionals who often are not adequately trained to evaluate, intervene, and manage patients in need of medical treatment (for acute medical, SUDs, or mental illness).
 

Recommendations for transporting high-risk patients

The legal and regulatory standards required by the Centers for Medicare & Medicaid Services guidelines⁸ for behavioral health patients are consistent in saying that law enforcement restraints cannot be used in hospital settings – unless the patient is under law enforcement custody. If the patient is admitted to an inpatient psychiatric unit, law enforcement restraints are never allowed to be used. Despite those guidelines for handling these situations within hospital settings, a similar standard does not exist for interhospital transport of high-risk behavioral health patients.

Patients often are transported between facilities by law enforcement, and at times, with the use of law enforcement restraints. However, use of law enforcement for interhospital transport of patients not in the custody of law enforcement is both detrimental to and clinically dangerous for the patient. Not only does the scenario put the patient at risk, but it also places law enforcement professionals at risk with the potential for legal liability if the patient medically decompensates during the transport.

Also, using law enforcement to intervene and provide transportation for behavioral health patients in crisis might cause further harm to the patient’s psychological condition and deter the patient from presenting for treatment.

The appropriate level of interfacility transport for a behavioral health patient requiring an inpatient level of care is secure transport with trained medical professionals. If necessary, restraint guidelines should follow the same standard as they do in hospital settings. In situations with high risk for violence or agitation, law enforcement should be requested to accompany EMS during the transport. Handling the situation in this way allows for a collaborative approach to provide adequate medical support, and provide for the physical safety and security of the patient – and of EMS personnel.

Across police and sheriffs’ departments nationwide, law enforcement officers are required to transport mental health patients from one location or hospital to another. Hospitals and outpatient locations, often with no alternative, rely on local law enforcement agencies to provide safe transport between acute and mental health facilities. Departmental policies and the widespread belief that mental health patients automatically pose a substantial danger to themselves or others have led to these patients being handcuffed and put in the back of police cruisers. Essentially, they are treated like criminals who are under arrest.

The CMS has strict criteria for ordering, applying, evaluating, reevaluating, and reporting restraint-associated deaths. Likewise, The Joint Commission, during its accreditation survey, rightly scrutinizes a facility’s use of restraints. Both the CMS and The Joint Commission define restraint by the function of the device and not the type of the device.

According to the CMS, a restraint is any manual method, physical or mechanic device, material, or equipment that immobilizes or reduces the ability of a patient to move his or her arms, legs, body, or head freely. Within a police cruiser, handcuffs on a mental health patient who is not under arrest would fall squarely within this definition of restraint.

A patient’s current behavior or clinical needs – not history or diagnosis – should determine whether a restraint is warranted. A patient experiencing a psychiatric crisis who is not under arrest might very well escalate and become destructive and combative when being placed in handcuffs in the back of a police vehicle. What should police do at that point? Should they arrest the individual? We offer the following five recommendations.
 

Key recommendations

• Patients who require interhospital transport for an acute behavioral health crisis should be transported by medical professionals with the training and expertise to manage mental health and medical conditions.
• Interhospital transport restraint guidelines should be in line with CMS guidelines for hospital restraints. No patient that is not under law enforcement custody should be transported in law enforcement restraints.
• Patients at high risk for violence/agitation (an underlying condition causing violence/agitation may include dementia, traumatic brain injuries, delirium, SUDs, or psychiatric conditions) should be managed in accordance with medically indicated intervention such as medical restraints or medications.
• If required, a request should be made for law enforcement officers to accompany EMS to provide support and to ensure the safety of the patient and EMS professionals during the transport.
• EMS professionals should receive specific training to manage acute psychiatric and SUD conditions, and should be aware of the life-threatening medical complications that can result from SUDs and psychiatric conditions/medications.

We recognize that patients with SMI require clinicians to work collaboratively, perhaps with law enforcement, to safely transport them from one point to another. Only when the rules we have outlined are followed will our patients get transported in such ways that allow them to get the care they need.
 

Dr. Norris is editor-in-chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Ms. Palmieri is a managing partner of Healthcare Legal Education & Consulting Network (HLECN), and the chief clinical officer and cofounder of XFERALL. HLECN focuses on clinical education and training, and XFERALL is a company that provides a technology platform aimed at improving access to care for behavioral health and medical patients. Ms. Slater is a managing partner of legal education for HLECN, and a trial attorney at Colley Shroyer & Abraham in Columbus, Ohio. Mr. Whaley is director of the safety and security department at GWU Hospital.

References

1. National Institute of Mental Health: Suicide.

2. National Institute on Drug Abuse. Overdose death rates. Revised January 2019.

3. Post by former NIMH Director Thomas Insel: No health without mental health. Sept. 6, 2011.

4. Dhar AK and Barton DA. Depression and the link with cardiovascular disease. Front Psychiatry. 2016 Mar 21;7:33.

5. Lichtman JH et al. Depression and coronary heart disease. Circulation. 2008;118:1768-75.

6. Hare DL et al. Depression and cardiovascular disease: A clinical review. European Heart J. 2014 Jun;35(21):1365-72.

7. “ ‘How many people have to die?’ SC mental health patients endure nightmare transport.” The News & Observer. 2019 May 29.

8. 42 C.F.R. Part 482. Part IV. Department of Health and Human Services. Medicare & Medicaid programs; Hospital conditions of participation; Patients’ rights; Final rule. 2006 Dec 8.

“I’ve given up, doctor. We gave it our best, but I am at the point where I want to end my life.” You receive this call at 2 a.m., and you’re flooded with a series of emotions and are bewildered – until your training kicks in.

Countless hours of working with patients in emergency department settings while on call as a resident inform your ability to triage the situation. Years of supervision guide your supportive statements as you work collaboratively with your patient to address the emotional and existential distress. As the call proceeds and you realize that your patient will require hospitalization, you are struck by a sobering question: “How am I going to arrange for my patient to go to the nearest hospital in the middle of the night?”

The options for transporting patients with serious mental illness (SMI) typically vary from bad to worse and usually filter down to three possibilities:

1. Get a friend or family member to transport them to the nearest ED.

2. Call emergency medical services (EMS) for transport to the nearest ED.

3. Call the police and request transport to the nearest ED.

Several factors would determine which of those options you would use alone or in combination. Current training paradigms for mental health professionals offer a limited body of literature on evidenced-based strategies for patients with SMI. Transporting high-risk psychiatric patients requires great care and respect, and in-depth knowledge about patients’ vulnerabilities. At best – if not handled properly – these experiences can aggravate patients’ mental health conditions. At worst, they can lead to the loss of our patients. Together, we have more than 40 years’ experience working in complex mental health care systems that run the gamut, from providing direct clinical care to directing mental health care divisions.

Sobering statistics prevail

In 2017, suicide was the 10th leading cause of death in the United States, accounting for more than 47,000 deaths. Suicide was the second-leading cause of death among individuals aged 10-34 and the fourth leading cause of death for individuals aged 35- 54.¹ In 2017, more than 70,200 Americans died from a drug overdose, including illicit drugs and prescription opioids.² Drug overdose deaths nearly quadrupled between 1999 and 2017, from 16,849 deaths to 70,237, respectively.²

The life expectancy of an American with SMI is 14-32 years less than that of the average population.³ Those numbers are on par with many sub-Saharan countries, including Sudan and Ethiopia, and surpass the health disparities for most racial and ethnic groups.

The decrease in life expectancy for people with SMI is rarely the result of suicide but rather the effect of medical comorbidities, including heart disease, stroke, pulmonary disease, diabetes, and cancer.³ Individuals with SMI are much more likely to suffer from chronic illnesses that are associated with co-occurring addictions, side effects of psychotropic medications, and social determinants of mental health, such as poverty.

Major depressive disorder among people with SMI presents acute and chronic medical risks. For example, people with major depressive disorder are at a higher risk for stroke and cardiovascular disease.⁴ There is a threefold increase in cardiac-related deaths for individuals who experience depression after a heart attack.⁵ In addition, depression increases the risk of cardiac-related death after a heart attack more than any other risk factor, except for congestive heart failure.⁶

The transportation challenge

When the complexity of psychiatric conditions is conceptualized to include decreased life expectancy because of medical comorbidities, medical complications that can result from psychotropic medications, and the high incidence of co-occurring substance use disorders (SUDs), it is clear why we are concerned about the type of transport used for patients experiencing a psychiatric emergency.

A common practice for patients presenting for medical treatment for a mental health condition is for them to be transported by law enforcement in handcuffs, or by private vehicle, because of a lack of medical transport options.

One tragic example occurred on Sept. 18, 2018, when two Horry County, S.C., deputies were providing a hospital-to-hospital transport for two mental health patients. The patients, who had no legal charges and were not under arrest, were locked in a transport cage in the back of a law enforcement vehicle for transport during Hurricane Florence. While the driver tried to move through floodwaters, the car stalled and became submerged. The patients were unable to open the locked cage door, and the deputies responsible for the transport did not have a key to unlock the cage.

The two women died as a result of the incident. Both deputies are facing two counts of involuntary manslaughter – with a potential prison sentence of 5 years each.⁷

The system that promotes the use of law enforcement to transport medical patients who are not in legal custody perpetuates a high risk to patients. Also at risk are law enforcement professionals who often are not adequately trained to evaluate, intervene, and manage patients in need of medical treatment (for acute medical, SUDs, or mental illness).
 

Recommendations for transporting high-risk patients

The legal and regulatory standards required by the Centers for Medicare & Medicaid Services guidelines⁸ for behavioral health patients are consistent in saying that law enforcement restraints cannot be used in hospital settings – unless the patient is under law enforcement custody. If the patient is admitted to an inpatient psychiatric unit, law enforcement restraints are never allowed to be used. Despite those guidelines for handling these situations within hospital settings, a similar standard does not exist for interhospital transport of high-risk behavioral health patients.

Patients often are transported between facilities by law enforcement, and at times, with the use of law enforcement restraints. However, use of law enforcement for interhospital transport of patients not in the custody of law enforcement is both detrimental to and clinically dangerous for the patient. Not only does the scenario put the patient at risk, but it also places law enforcement professionals at risk with the potential for legal liability if the patient medically decompensates during the transport.

Also, using law enforcement to intervene and provide transportation for behavioral health patients in crisis might cause further harm to the patient’s psychological condition and deter the patient from presenting for treatment.

The appropriate level of interfacility transport for a behavioral health patient requiring an inpatient level of care is secure transport with trained medical professionals. If necessary, restraint guidelines should follow the same standard as they do in hospital settings. In situations with high risk for violence or agitation, law enforcement should be requested to accompany EMS during the transport. Handling the situation in this way allows for a collaborative approach to provide adequate medical support, and provide for the physical safety and security of the patient – and of EMS personnel.

Across police and sheriffs’ departments nationwide, law enforcement officers are required to transport mental health patients from one location or hospital to another. Hospitals and outpatient locations, often with no alternative, rely on local law enforcement agencies to provide safe transport between acute and mental health facilities. Departmental policies and the widespread belief that mental health patients automatically pose a substantial danger to themselves or others have led to these patients being handcuffed and put in the back of police cruisers. Essentially, they are treated like criminals who are under arrest.

The CMS has strict criteria for ordering, applying, evaluating, reevaluating, and reporting restraint-associated deaths. Likewise, The Joint Commission, during its accreditation survey, rightly scrutinizes a facility’s use of restraints. Both the CMS and The Joint Commission define restraint by the function of the device and not the type of the device.

According to the CMS, a restraint is any manual method, physical or mechanic device, material, or equipment that immobilizes or reduces the ability of a patient to move his or her arms, legs, body, or head freely. Within a police cruiser, handcuffs on a mental health patient who is not under arrest would fall squarely within this definition of restraint.

A patient’s current behavior or clinical needs – not history or diagnosis – should determine whether a restraint is warranted. A patient experiencing a psychiatric crisis who is not under arrest might very well escalate and become destructive and combative when being placed in handcuffs in the back of a police vehicle. What should police do at that point? Should they arrest the individual? We offer the following five recommendations.
 

Key recommendations

• Patients who require interhospital transport for an acute behavioral health crisis should be transported by medical professionals with the training and expertise to manage mental health and medical conditions.
• Interhospital transport restraint guidelines should be in line with CMS guidelines for hospital restraints. No patient that is not under law enforcement custody should be transported in law enforcement restraints.
• Patients at high risk for violence/agitation (an underlying condition causing violence/agitation may include dementia, traumatic brain injuries, delirium, SUDs, or psychiatric conditions) should be managed in accordance with medically indicated intervention such as medical restraints or medications.
• If required, a request should be made for law enforcement officers to accompany EMS to provide support and to ensure the safety of the patient and EMS professionals during the transport.
• EMS professionals should receive specific training to manage acute psychiatric and SUD conditions, and should be aware of the life-threatening medical complications that can result from SUDs and psychiatric conditions/medications.

We recognize that patients with SMI require clinicians to work collaboratively, perhaps with law enforcement, to safely transport them from one point to another. Only when the rules we have outlined are followed will our patients get transported in such ways that allow them to get the care they need.
 

Dr. Norris is editor-in-chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Ms. Palmieri is a managing partner of Healthcare Legal Education & Consulting Network (HLECN), and the chief clinical officer and cofounder of XFERALL. HLECN focuses on clinical education and training, and XFERALL is a company that provides a technology platform aimed at improving access to care for behavioral health and medical patients. Ms. Slater is a managing partner of legal education for HLECN, and a trial attorney at Colley Shroyer & Abraham in Columbus, Ohio. Mr. Whaley is director of the safety and security department at GWU Hospital.

References

1. National Institute of Mental Health: Suicide.

2. National Institute on Drug Abuse. Overdose death rates. Revised January 2019.

3. Post by former NIMH Director Thomas Insel: No health without mental health. Sept. 6, 2011.

4. Dhar AK and Barton DA. Depression and the link with cardiovascular disease. Front Psychiatry. 2016 Mar 21;7:33.

5. Lichtman JH et al. Depression and coronary heart disease. Circulation. 2008;118:1768-75.

6. Hare DL et al. Depression and cardiovascular disease: A clinical review. European Heart J. 2014 Jun;35(21):1365-72.

7. “ ‘How many people have to die?’ SC mental health patients endure nightmare transport.” The News & Observer. 2019 May 29.

8. 42 C.F.R. Part 482. Part IV. Department of Health and Human Services. Medicare & Medicaid programs; Hospital conditions of participation; Patients’ rights; Final rule. 2006 Dec 8.

“I’ve given up, doctor. We gave it our best, but I am at the point where I want to end my life.” You receive this call at 2 a.m., and you’re flooded with a series of emotions and are bewildered – until your training kicks in.

Countless hours of working with patients in emergency department settings while on call as a resident inform your ability to triage the situation. Years of supervision guide your supportive statements as you work collaboratively with your patient to address the emotional and existential distress. As the call proceeds and you realize that your patient will require hospitalization, you are struck by a sobering question: “How am I going to arrange for my patient to go to the nearest hospital in the middle of the night?”

The options for transporting patients with serious mental illness (SMI) typically vary from bad to worse and usually filter down to three possibilities:

1. Get a friend or family member to transport them to the nearest ED.

2. Call emergency medical services (EMS) for transport to the nearest ED.

3. Call the police and request transport to the nearest ED.

Several factors would determine which of those options you would use alone or in combination. Current training paradigms for mental health professionals offer a limited body of literature on evidenced-based strategies for patients with SMI. Transporting high-risk psychiatric patients requires great care and respect, and in-depth knowledge about patients’ vulnerabilities. At best – if not handled properly – these experiences can aggravate patients’ mental health conditions. At worst, they can lead to the loss of our patients. Together, we have more than 40 years’ experience working in complex mental health care systems that run the gamut, from providing direct clinical care to directing mental health care divisions.

Sobering statistics prevail

In 2017, suicide was the 10th leading cause of death in the United States, accounting for more than 47,000 deaths. Suicide was the second-leading cause of death among individuals aged 10-34 and the fourth leading cause of death for individuals aged 35- 54.¹ In 2017, more than 70,200 Americans died from a drug overdose, including illicit drugs and prescription opioids.² Drug overdose deaths nearly quadrupled between 1999 and 2017, from 16,849 deaths to 70,237, respectively.²

The life expectancy of an American with SMI is 14-32 years less than that of the average population.³ Those numbers are on par with many sub-Saharan countries, including Sudan and Ethiopia, and surpass the health disparities for most racial and ethnic groups.

The decrease in life expectancy for people with SMI is rarely the result of suicide but rather the effect of medical comorbidities, including heart disease, stroke, pulmonary disease, diabetes, and cancer.³ Individuals with SMI are much more likely to suffer from chronic illnesses that are associated with co-occurring addictions, side effects of psychotropic medications, and social determinants of mental health, such as poverty.

Major depressive disorder among people with SMI presents acute and chronic medical risks. For example, people with major depressive disorder are at a higher risk for stroke and cardiovascular disease.⁴ There is a threefold increase in cardiac-related deaths for individuals who experience depression after a heart attack.⁵ In addition, depression increases the risk of cardiac-related death after a heart attack more than any other risk factor, except for congestive heart failure.⁶

The transportation challenge

When the complexity of psychiatric conditions is conceptualized to include decreased life expectancy because of medical comorbidities, medical complications that can result from psychotropic medications, and the high incidence of co-occurring substance use disorders (SUDs), it is clear why we are concerned about the type of transport used for patients experiencing a psychiatric emergency.

A common practice for patients presenting for medical treatment for a mental health condition is for them to be transported by law enforcement in handcuffs, or by private vehicle, because of a lack of medical transport options.

One tragic example occurred on Sept. 18, 2018, when two Horry County, S.C., deputies were providing a hospital-to-hospital transport for two mental health patients. The patients, who had no legal charges and were not under arrest, were locked in a transport cage in the back of a law enforcement vehicle for transport during Hurricane Florence. While the driver tried to move through floodwaters, the car stalled and became submerged. The patients were unable to open the locked cage door, and the deputies responsible for the transport did not have a key to unlock the cage.

The two women died as a result of the incident. Both deputies are facing two counts of involuntary manslaughter – with a potential prison sentence of 5 years each.⁷

The system that promotes the use of law enforcement to transport medical patients who are not in legal custody perpetuates a high risk to patients. Also at risk are law enforcement professionals who often are not adequately trained to evaluate, intervene, and manage patients in need of medical treatment (for acute medical, SUDs, or mental illness).
 

Recommendations for transporting high-risk patients

The legal and regulatory standards required by the Centers for Medicare & Medicaid Services guidelines⁸ for behavioral health patients are consistent in saying that law enforcement restraints cannot be used in hospital settings – unless the patient is under law enforcement custody. If the patient is admitted to an inpatient psychiatric unit, law enforcement restraints are never allowed to be used. Despite those guidelines for handling these situations within hospital settings, a similar standard does not exist for interhospital transport of high-risk behavioral health patients.

Patients often are transported between facilities by law enforcement, and at times, with the use of law enforcement restraints. However, use of law enforcement for interhospital transport of patients not in the custody of law enforcement is both detrimental to and clinically dangerous for the patient. Not only does the scenario put the patient at risk, but it also places law enforcement professionals at risk with the potential for legal liability if the patient medically decompensates during the transport.

Also, using law enforcement to intervene and provide transportation for behavioral health patients in crisis might cause further harm to the patient’s psychological condition and deter the patient from presenting for treatment.

The appropriate level of interfacility transport for a behavioral health patient requiring an inpatient level of care is secure transport with trained medical professionals. If necessary, restraint guidelines should follow the same standard as they do in hospital settings. In situations with high risk for violence or agitation, law enforcement should be requested to accompany EMS during the transport. Handling the situation in this way allows for a collaborative approach to provide adequate medical support, and provide for the physical safety and security of the patient – and of EMS personnel.

Across police and sheriffs’ departments nationwide, law enforcement officers are required to transport mental health patients from one location or hospital to another. Hospitals and outpatient locations, often with no alternative, rely on local law enforcement agencies to provide safe transport between acute and mental health facilities. Departmental policies and the widespread belief that mental health patients automatically pose a substantial danger to themselves or others have led to these patients being handcuffed and put in the back of police cruisers. Essentially, they are treated like criminals who are under arrest.

The CMS has strict criteria for ordering, applying, evaluating, reevaluating, and reporting restraint-associated deaths. Likewise, The Joint Commission, during its accreditation survey, rightly scrutinizes a facility’s use of restraints. Both the CMS and The Joint Commission define restraint by the function of the device and not the type of the device.

According to the CMS, a restraint is any manual method, physical or mechanic device, material, or equipment that immobilizes or reduces the ability of a patient to move his or her arms, legs, body, or head freely. Within a police cruiser, handcuffs on a mental health patient who is not under arrest would fall squarely within this definition of restraint.

A patient’s current behavior or clinical needs – not history or diagnosis – should determine whether a restraint is warranted. A patient experiencing a psychiatric crisis who is not under arrest might very well escalate and become destructive and combative when being placed in handcuffs in the back of a police vehicle. What should police do at that point? Should they arrest the individual? We offer the following five recommendations.
 

Key recommendations

• Patients who require interhospital transport for an acute behavioral health crisis should be transported by medical professionals with the training and expertise to manage mental health and medical conditions.
• Interhospital transport restraint guidelines should be in line with CMS guidelines for hospital restraints. No patient that is not under law enforcement custody should be transported in law enforcement restraints.
• Patients at high risk for violence/agitation (an underlying condition causing violence/agitation may include dementia, traumatic brain injuries, delirium, SUDs, or psychiatric conditions) should be managed in accordance with medically indicated intervention such as medical restraints or medications.
• If required, a request should be made for law enforcement officers to accompany EMS to provide support and to ensure the safety of the patient and EMS professionals during the transport.
• EMS professionals should receive specific training to manage acute psychiatric and SUD conditions, and should be aware of the life-threatening medical complications that can result from SUDs and psychiatric conditions/medications.

We recognize that patients with SMI require clinicians to work collaboratively, perhaps with law enforcement, to safely transport them from one point to another. Only when the rules we have outlined are followed will our patients get transported in such ways that allow them to get the care they need.
 

Dr. Norris is editor-in-chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Ms. Palmieri is a managing partner of Healthcare Legal Education & Consulting Network (HLECN), and the chief clinical officer and cofounder of XFERALL. HLECN focuses on clinical education and training, and XFERALL is a company that provides a technology platform aimed at improving access to care for behavioral health and medical patients. Ms. Slater is a managing partner of legal education for HLECN, and a trial attorney at Colley Shroyer & Abraham in Columbus, Ohio. Mr. Whaley is director of the safety and security department at GWU Hospital.

References

1. National Institute of Mental Health: Suicide.

2. National Institute on Drug Abuse. Overdose death rates. Revised January 2019.

3. Post by former NIMH Director Thomas Insel: No health without mental health. Sept. 6, 2011.

4. Dhar AK and Barton DA. Depression and the link with cardiovascular disease. Front Psychiatry. 2016 Mar 21;7:33.

5. Lichtman JH et al. Depression and coronary heart disease. Circulation. 2008;118:1768-75.

6. Hare DL et al. Depression and cardiovascular disease: A clinical review. European Heart J. 2014 Jun;35(21):1365-72.

7. “ ‘How many people have to die?’ SC mental health patients endure nightmare transport.” The News & Observer. 2019 May 29.

8. 42 C.F.R. Part 482. Part IV. Department of Health and Human Services. Medicare & Medicaid programs; Hospital conditions of participation; Patients’ rights; Final rule. 2006 Dec 8.

It’s an honor and a great pleasure to take on this new role as editor in chief for Hematology News. When I got the call from our outgoing editor Matt Kalaycio, MD, a year ago asking me to consider stepping into his shoes a few things flashed through my mind. Will I do this role justice? Do I have what it takes to be a great editor in chief?

Then I thought – will there be time to learn the ropes or will this be like most of my career positions where you jump into the water first and figure out how to swim later? I never once thought: “Oh no … I cannot do this and I’m going to say no!” So here I am today, reporting for duty as the editor in chief of Hematology News.

I was once accused of being “intellectually restless” which is a badge I wear with honor and is perhaps a trait I learned from my mom who was a public health nurse in Nigeria back in the seventies. She broke a lot of glass ceilings in her day – Cornell University–trained advanced practice nurse, mother of five girls, with a degree in textile and design and business accounting. She also got a certificate in baking and cake decorating and she used all her skills and certifications to raise her daughters to believe the sky was the limit.

Mom started one of the first licensed practical nursing (LPN) schools in Nigeria and I learned from her to never back down from a challenge – on a dare I got my LPN certification before I went to medical school.

You see I love a challenge and an adventure and serving as the editor in chief for Hematology News provides me with an amazing platform and opportunity to achieve a lot of firsts and satisfy that hunger to make a global difference that has always guided my career.

I’ve thought long and hard about what and how I envision this role shaping out. What do I want our readers to take away from this newspaper under my leadership? What common themes will be woven in every edition? I want our readers to be challenged and keep learning. Not just about hematologic disorders and the latest scientific breakthroughs that drive improved patient outcomes for blood disorders but also about the intersectionality between hematology and other life disciplines.

I remember taking an art class in high school learning about dimensions and proportions of buildings and I dreamt of becoming an architect. Fast forward 2 decades later, I attended a medical conference at Georgia Institute of Technology in Atlanta and was enthralled at how various sessions demonstrated how art, engineering and architecture played a role in the development and design of orthopedic prosthesis used in amputees. I learned how engineering shaped our understanding of microfluidics, something that is now being leveraged in drug delivery science and in the field of hematology.

I want our readers to keep learning not just from esteemed scientists and clinicians but from various stakeholders – the patient, the high school student, the spouse of the hematologist, not to mention our residents and fellows, who are the future of our discipline. Furthermore, I want our readers to see the human side of hematology – the face behind the scientist or clinician and the reality of what joys and tolls we experience in this field.

A Fall 2019 Medscape survey cited the prevalence of physician burnout among hematology oncology physicians: 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed. These are statistics that cannot be ignored or minimized a they ultimately have a profound impact on patient outcomes. You see, I really believe that much of the success we have in healing our patients relies not just on the medications we prescribe or on the procedures we perform or the science we leverage. Much of healing in medicine and in hematology is based on the secret sauce of being humane – defined by Merriam-Webster dictionary as the character trait that is “marked by demonstrating compassion, sympathy, or consideration for humans or animals.”

So, to sum up what to expect in the coming year from your editor in chief? Look out for some thought-provoking, fun, and unusual perspectives that are aimed to keep us learning, growing, and remaining humane in our interactions with our patients, each other, but more importantly with ourselves. #bringit2020 #HematologyNews #NewEditorInChiefPerspectives.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

It’s an honor and a great pleasure to take on this new role as editor in chief for Hematology News. When I got the call from our outgoing editor Matt Kalaycio, MD, a year ago asking me to consider stepping into his shoes a few things flashed through my mind. Will I do this role justice? Do I have what it takes to be a great editor in chief?

Then I thought – will there be time to learn the ropes or will this be like most of my career positions where you jump into the water first and figure out how to swim later? I never once thought: “Oh no … I cannot do this and I’m going to say no!” So here I am today, reporting for duty as the editor in chief of Hematology News.

I was once accused of being “intellectually restless” which is a badge I wear with honor and is perhaps a trait I learned from my mom who was a public health nurse in Nigeria back in the seventies. She broke a lot of glass ceilings in her day – Cornell University–trained advanced practice nurse, mother of five girls, with a degree in textile and design and business accounting. She also got a certificate in baking and cake decorating and she used all her skills and certifications to raise her daughters to believe the sky was the limit.

Mom started one of the first licensed practical nursing (LPN) schools in Nigeria and I learned from her to never back down from a challenge – on a dare I got my LPN certification before I went to medical school.

You see I love a challenge and an adventure and serving as the editor in chief for Hematology News provides me with an amazing platform and opportunity to achieve a lot of firsts and satisfy that hunger to make a global difference that has always guided my career.

I’ve thought long and hard about what and how I envision this role shaping out. What do I want our readers to take away from this newspaper under my leadership? What common themes will be woven in every edition? I want our readers to be challenged and keep learning. Not just about hematologic disorders and the latest scientific breakthroughs that drive improved patient outcomes for blood disorders but also about the intersectionality between hematology and other life disciplines.

I remember taking an art class in high school learning about dimensions and proportions of buildings and I dreamt of becoming an architect. Fast forward 2 decades later, I attended a medical conference at Georgia Institute of Technology in Atlanta and was enthralled at how various sessions demonstrated how art, engineering and architecture played a role in the development and design of orthopedic prosthesis used in amputees. I learned how engineering shaped our understanding of microfluidics, something that is now being leveraged in drug delivery science and in the field of hematology.

I want our readers to keep learning not just from esteemed scientists and clinicians but from various stakeholders – the patient, the high school student, the spouse of the hematologist, not to mention our residents and fellows, who are the future of our discipline. Furthermore, I want our readers to see the human side of hematology – the face behind the scientist or clinician and the reality of what joys and tolls we experience in this field.

A Fall 2019 Medscape survey cited the prevalence of physician burnout among hematology oncology physicians: 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed. These are statistics that cannot be ignored or minimized a they ultimately have a profound impact on patient outcomes. You see, I really believe that much of the success we have in healing our patients relies not just on the medications we prescribe or on the procedures we perform or the science we leverage. Much of healing in medicine and in hematology is based on the secret sauce of being humane – defined by Merriam-Webster dictionary as the character trait that is “marked by demonstrating compassion, sympathy, or consideration for humans or animals.”

So, to sum up what to expect in the coming year from your editor in chief? Look out for some thought-provoking, fun, and unusual perspectives that are aimed to keep us learning, growing, and remaining humane in our interactions with our patients, each other, but more importantly with ourselves. #bringit2020 #HematologyNews #NewEditorInChiefPerspectives.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

It’s an honor and a great pleasure to take on this new role as editor in chief for Hematology News. When I got the call from our outgoing editor Matt Kalaycio, MD, a year ago asking me to consider stepping into his shoes a few things flashed through my mind. Will I do this role justice? Do I have what it takes to be a great editor in chief?

Then I thought – will there be time to learn the ropes or will this be like most of my career positions where you jump into the water first and figure out how to swim later? I never once thought: “Oh no … I cannot do this and I’m going to say no!” So here I am today, reporting for duty as the editor in chief of Hematology News.

I was once accused of being “intellectually restless” which is a badge I wear with honor and is perhaps a trait I learned from my mom who was a public health nurse in Nigeria back in the seventies. She broke a lot of glass ceilings in her day – Cornell University–trained advanced practice nurse, mother of five girls, with a degree in textile and design and business accounting. She also got a certificate in baking and cake decorating and she used all her skills and certifications to raise her daughters to believe the sky was the limit.

Mom started one of the first licensed practical nursing (LPN) schools in Nigeria and I learned from her to never back down from a challenge – on a dare I got my LPN certification before I went to medical school.

You see I love a challenge and an adventure and serving as the editor in chief for Hematology News provides me with an amazing platform and opportunity to achieve a lot of firsts and satisfy that hunger to make a global difference that has always guided my career.

I’ve thought long and hard about what and how I envision this role shaping out. What do I want our readers to take away from this newspaper under my leadership? What common themes will be woven in every edition? I want our readers to be challenged and keep learning. Not just about hematologic disorders and the latest scientific breakthroughs that drive improved patient outcomes for blood disorders but also about the intersectionality between hematology and other life disciplines.

I remember taking an art class in high school learning about dimensions and proportions of buildings and I dreamt of becoming an architect. Fast forward 2 decades later, I attended a medical conference at Georgia Institute of Technology in Atlanta and was enthralled at how various sessions demonstrated how art, engineering and architecture played a role in the development and design of orthopedic prosthesis used in amputees. I learned how engineering shaped our understanding of microfluidics, something that is now being leveraged in drug delivery science and in the field of hematology.

I want our readers to keep learning not just from esteemed scientists and clinicians but from various stakeholders – the patient, the high school student, the spouse of the hematologist, not to mention our residents and fellows, who are the future of our discipline. Furthermore, I want our readers to see the human side of hematology – the face behind the scientist or clinician and the reality of what joys and tolls we experience in this field.

A Fall 2019 Medscape survey cited the prevalence of physician burnout among hematology oncology physicians: 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed. These are statistics that cannot be ignored or minimized a they ultimately have a profound impact on patient outcomes. You see, I really believe that much of the success we have in healing our patients relies not just on the medications we prescribe or on the procedures we perform or the science we leverage. Much of healing in medicine and in hematology is based on the secret sauce of being humane – defined by Merriam-Webster dictionary as the character trait that is “marked by demonstrating compassion, sympathy, or consideration for humans or animals.”

So, to sum up what to expect in the coming year from your editor in chief? Look out for some thought-provoking, fun, and unusual perspectives that are aimed to keep us learning, growing, and remaining humane in our interactions with our patients, each other, but more importantly with ourselves. #bringit2020 #HematologyNews #NewEditorInChiefPerspectives.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

The Diagnosis: Netherton Syndrome  

Netherton syndrome (NS) is a rare autosomal-recessive disorder characterized by a clinical triad of ichthyosis linearis circumflexa; atopic diathesis; and hair shaft abnormalities, most classically trichorrhexis invaginata.¹ Netherton syndrome is caused by a loss-of-function mutation in the serine peptidase inhibitor Kazal-type gene, SPINK5, which encodes LEKTI proteins and is found in all stratified epithelia as well as the thymus.² A lack of functional LEKTI leads to the activation of a cascade of allergy and inflammation as well as uncontrolled proteolytic activity in the stratum corneum, which causes increased desquamation.¹  

Netherton syndrome presents with serpiginous or circinate scaling plaques with double-edged scale referred to as ichthyosis linearis circumflexa (quiz image). Skin plaques are intensely pruritic and migratory with fluctuating severity. Alternately, patients may have a generalized scaling erythroderma. Infants are at an especially high risk for recurrent infections, sepsis, hypernatremic dehydration, and failure to thrive.²  

Netherton syndrome often gradually improves over time, though adults with NS usually have intensely pruritic, localized patches of redness, scaling, or ichthyosis linearis circumflexa. Lichenification and eczematous plaques of the popliteal and antecubital fossae also are common.¹ Therapeutic options for NS include emollients, topical steroids, phototherapy, and intravenous immunoglobulin for severe cases.³ Because there is skin barrier dysfunction in NS, supratherapeutic serum levels of tacrolimus following topical application have been reported.⁴ Topical pimecrolimus has been demonstrated as an effective and safer application.⁵ Trichorrhexis invaginata (also known as bamboo hair) of the hair and eyebrows is a pathognomonic finding in NS, involving invagination of the distal hair shaft into the proximal shaft on light microscopy examination.¹ 

Histopathology is variable and nonspecific with psoriasiform hyperplasia as the most frequent finding. Other histologic findings include incomplete keratinization of the epidermis, incomplete cornification with a severely reduced granular layer, and mild to moderate inflammatory dermal infiltrate.⁶ LEKTI immunostaining is confirmatory and shows the reduction or complete absence of LEKTI in the granular layer and inner root sheath of follicles.¹ Patchy LEKTI staining would be suggestive of atopic dermatitis and psoriasis instead of NS.² 

Atopic manifestations include angioedema, urticaria, and anaphylaxis, as well as chronic diarrhea or vomiting due to food allergies.1 Elevated IgE levels for staple foods (eg, milk, wheat), elevated total serum IgE, and eosinophilia frequently are seen.⁷ Biopsy of the esophagus and colon likely would show mucosal eosinophilia.^7,8 Elimination of major food triggers through specific serum IgE testing and oral allergen desensitization can lead to the reduction of digestive symptoms.⁹ Cisapride and omeprazole are effective treatments for gastroesophageal reflux and poor feeding.⁸ Biopsy of the intestines in this patient likely would not have shown total villous atrophy, which is rare and primarily reported in infants with NS who have failure to thrive.¹⁰ There is a limited association between NS and intestinal metaplasia, intraepithelial lymphocytes, and bacterial overgrowth. 

The primary morphology of dyskeratosis follicularis includes keratotic papules developing in sebaceous areas of the skin rather than scaly serpiginous plaques as seen in NS. Elastosis perforans serpiginosa is a perforating disorder seen in the context of several genetic conditions. It has a serpiginous appearance but, unlike NS, tends to be localized and features keratotic papules rather than patches with scale. Erythema marginatum is an uncommon feature of rheumatic fever and appears as pink annular macules and tends not to be pruritic. Subacute cutaneous lupus does feature scaly annular and serpiginous plaques but features trailing scale without the double-edge appearance of NS and is acquired rather than genetic.

The Diagnosis: Netherton Syndrome  

Netherton syndrome (NS) is a rare autosomal-recessive disorder characterized by a clinical triad of ichthyosis linearis circumflexa; atopic diathesis; and hair shaft abnormalities, most classically trichorrhexis invaginata.¹ Netherton syndrome is caused by a loss-of-function mutation in the serine peptidase inhibitor Kazal-type gene, SPINK5, which encodes LEKTI proteins and is found in all stratified epithelia as well as the thymus.² A lack of functional LEKTI leads to the activation of a cascade of allergy and inflammation as well as uncontrolled proteolytic activity in the stratum corneum, which causes increased desquamation.¹  

Netherton syndrome presents with serpiginous or circinate scaling plaques with double-edged scale referred to as ichthyosis linearis circumflexa (quiz image). Skin plaques are intensely pruritic and migratory with fluctuating severity. Alternately, patients may have a generalized scaling erythroderma. Infants are at an especially high risk for recurrent infections, sepsis, hypernatremic dehydration, and failure to thrive.²  

Netherton syndrome often gradually improves over time, though adults with NS usually have intensely pruritic, localized patches of redness, scaling, or ichthyosis linearis circumflexa. Lichenification and eczematous plaques of the popliteal and antecubital fossae also are common.¹ Therapeutic options for NS include emollients, topical steroids, phototherapy, and intravenous immunoglobulin for severe cases.³ Because there is skin barrier dysfunction in NS, supratherapeutic serum levels of tacrolimus following topical application have been reported.⁴ Topical pimecrolimus has been demonstrated as an effective and safer application.⁵ Trichorrhexis invaginata (also known as bamboo hair) of the hair and eyebrows is a pathognomonic finding in NS, involving invagination of the distal hair shaft into the proximal shaft on light microscopy examination.¹ 

Histopathology is variable and nonspecific with psoriasiform hyperplasia as the most frequent finding. Other histologic findings include incomplete keratinization of the epidermis, incomplete cornification with a severely reduced granular layer, and mild to moderate inflammatory dermal infiltrate.⁶ LEKTI immunostaining is confirmatory and shows the reduction or complete absence of LEKTI in the granular layer and inner root sheath of follicles.¹ Patchy LEKTI staining would be suggestive of atopic dermatitis and psoriasis instead of NS.² 

Atopic manifestations include angioedema, urticaria, and anaphylaxis, as well as chronic diarrhea or vomiting due to food allergies.1 Elevated IgE levels for staple foods (eg, milk, wheat), elevated total serum IgE, and eosinophilia frequently are seen.⁷ Biopsy of the esophagus and colon likely would show mucosal eosinophilia.^7,8 Elimination of major food triggers through specific serum IgE testing and oral allergen desensitization can lead to the reduction of digestive symptoms.⁹ Cisapride and omeprazole are effective treatments for gastroesophageal reflux and poor feeding.⁸ Biopsy of the intestines in this patient likely would not have shown total villous atrophy, which is rare and primarily reported in infants with NS who have failure to thrive.¹⁰ There is a limited association between NS and intestinal metaplasia, intraepithelial lymphocytes, and bacterial overgrowth. 

The primary morphology of dyskeratosis follicularis includes keratotic papules developing in sebaceous areas of the skin rather than scaly serpiginous plaques as seen in NS. Elastosis perforans serpiginosa is a perforating disorder seen in the context of several genetic conditions. It has a serpiginous appearance but, unlike NS, tends to be localized and features keratotic papules rather than patches with scale. Erythema marginatum is an uncommon feature of rheumatic fever and appears as pink annular macules and tends not to be pruritic. Subacute cutaneous lupus does feature scaly annular and serpiginous plaques but features trailing scale without the double-edge appearance of NS and is acquired rather than genetic.

The Diagnosis: Netherton Syndrome  

Netherton syndrome (NS) is a rare autosomal-recessive disorder characterized by a clinical triad of ichthyosis linearis circumflexa; atopic diathesis; and hair shaft abnormalities, most classically trichorrhexis invaginata.¹ Netherton syndrome is caused by a loss-of-function mutation in the serine peptidase inhibitor Kazal-type gene, SPINK5, which encodes LEKTI proteins and is found in all stratified epithelia as well as the thymus.² A lack of functional LEKTI leads to the activation of a cascade of allergy and inflammation as well as uncontrolled proteolytic activity in the stratum corneum, which causes increased desquamation.¹  

Netherton syndrome presents with serpiginous or circinate scaling plaques with double-edged scale referred to as ichthyosis linearis circumflexa (quiz image). Skin plaques are intensely pruritic and migratory with fluctuating severity. Alternately, patients may have a generalized scaling erythroderma. Infants are at an especially high risk for recurrent infections, sepsis, hypernatremic dehydration, and failure to thrive.²  

Netherton syndrome often gradually improves over time, though adults with NS usually have intensely pruritic, localized patches of redness, scaling, or ichthyosis linearis circumflexa. Lichenification and eczematous plaques of the popliteal and antecubital fossae also are common.¹ Therapeutic options for NS include emollients, topical steroids, phototherapy, and intravenous immunoglobulin for severe cases.³ Because there is skin barrier dysfunction in NS, supratherapeutic serum levels of tacrolimus following topical application have been reported.⁴ Topical pimecrolimus has been demonstrated as an effective and safer application.⁵ Trichorrhexis invaginata (also known as bamboo hair) of the hair and eyebrows is a pathognomonic finding in NS, involving invagination of the distal hair shaft into the proximal shaft on light microscopy examination.¹ 

Histopathology is variable and nonspecific with psoriasiform hyperplasia as the most frequent finding. Other histologic findings include incomplete keratinization of the epidermis, incomplete cornification with a severely reduced granular layer, and mild to moderate inflammatory dermal infiltrate.⁶ LEKTI immunostaining is confirmatory and shows the reduction or complete absence of LEKTI in the granular layer and inner root sheath of follicles.¹ Patchy LEKTI staining would be suggestive of atopic dermatitis and psoriasis instead of NS.² 

Atopic manifestations include angioedema, urticaria, and anaphylaxis, as well as chronic diarrhea or vomiting due to food allergies.1 Elevated IgE levels for staple foods (eg, milk, wheat), elevated total serum IgE, and eosinophilia frequently are seen.⁷ Biopsy of the esophagus and colon likely would show mucosal eosinophilia.^7,8 Elimination of major food triggers through specific serum IgE testing and oral allergen desensitization can lead to the reduction of digestive symptoms.⁹ Cisapride and omeprazole are effective treatments for gastroesophageal reflux and poor feeding.⁸ Biopsy of the intestines in this patient likely would not have shown total villous atrophy, which is rare and primarily reported in infants with NS who have failure to thrive.¹⁰ There is a limited association between NS and intestinal metaplasia, intraepithelial lymphocytes, and bacterial overgrowth. 

The primary morphology of dyskeratosis follicularis includes keratotic papules developing in sebaceous areas of the skin rather than scaly serpiginous plaques as seen in NS. Elastosis perforans serpiginosa is a perforating disorder seen in the context of several genetic conditions. It has a serpiginous appearance but, unlike NS, tends to be localized and features keratotic papules rather than patches with scale. Erythema marginatum is an uncommon feature of rheumatic fever and appears as pink annular macules and tends not to be pruritic. Subacute cutaneous lupus does feature scaly annular and serpiginous plaques but features trailing scale without the double-edge appearance of NS and is acquired rather than genetic.

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

On March 4, 2020, the Supreme Court of the United States (SCOTUS) will hear opening arguments for June Medical Services v. Russo. (Please note that this case was originally referred to as June Medical Services v. Gee. However, Secretary Rebekah Gee resigned from her position on January 31, 2020, and was replaced by Interim Secretary Stephen Russo.) The case will examine a Louisiana law (Louisiana Act 620, or LA 620), originally passed in 2014, that requires physicians to have hospital admitting privileges within 30 miles of where they provide abortion services.¹ When LA 620 was signed into law in 2014, 5 of Louisiana’s 6 abortion clinics would not have met the standards created by this legislation and would have been forced to close, potentially leaving the vast majority of women in Louisiana without access to an abortion provider, and disproportionately impacting poor and rural women. Prior to enactment of this law, physicians at these 5 clinics attempted to obtain admitting privileges, and all were denied. The denials occurred due to two main reasons—because the providers admitted too few patients each year to qualify for hospital privileges or simply because they provided abortion care.² Shortly after this legislation was signed into law, the Center for Reproductive Rights (CRR) challenged the law, citing the undue burden it created for patients attempting to access abortion care.
 

Prior case also considered question of hospital privileges for abortion providers

Interestingly, SCOTUS already has ruled on this very question. In 1992, the Court ruled in Planned Parenthood of Southeastern Pennsylvania v. Casey that it is unconstitutional for a state to create an “undue burden” on a woman’s right to abortion prior to fetal viability.³ And in 2016, when considering whether or not requiring abortion providers to obtain hospital privileges creates an undue burden in Whole Women’s Health (WWH) v. Hellerstedt, the Supreme Court’s answer was yes, it does. WWH, with legal aid from CRR, challenged Texas House Bill 2 (H.B. 2), which similar to LA 620, required abortion providers to have local admitting privileges. Based largely on the precedent set in Casey, SCOTUS ruled 5-3 in favor of WWH.

The Louisiana law currently in question was written and challenged in district court simultaneous to the Supreme Court’s review of WWH. The district court declared LA 620 invalid and permanently enjoined its enforcement, finding the law would “drastically burden women’s right to choose abortions.”⁴ However, the US Court of Appeals for the Fifth Circuit reviewed the case and overturned the district court decision, finding the lower court’s analysis erroneous and stating, “no clinics will likely be forced to close on account of [LA 620].” The Fifth Circuit panel ruled that, despite the precedent of WWH, LA 620 did not create an undue burden because of state-level differences in admitting privileges, demographics, and geography. They also found that only 30% of the 2 million women living in Louisiana would be impacted by the law, predominantly via longer wait times, and argued that this does not represent significant burden. The plaintiffs filed for an emergency stay with SCOTUS, who granted the stay pending a full hearing. On March 4, the Supreme Court will hear arguments to determine if the Fifth Circuit was correct in drawing a distinction between LA 620 and the SCOTUS verdict in WWH.

Targeted restrictions on abortion providers

LA 620 joins a long series of laws meant to enact targeted restrictions on abortion providers, or “TRAP” laws. TRAP laws are written to limit access to abortion under the guise of improving patient safety, despite ample evidence to the contrary, and include such various regulations as admitting privileges, facilities requirements, waiting periods, and parental or partner notification. Many such laws have been enacted in the last decade, and many struck down based on judicial precedent.

How the Supreme Court has ruled in the past

When a case is appealed to the Supreme Court, the court can either decline to hear the case, thereby leaving the lower courts’ ruling in place, or choose to hear the case in full and either affirm or overturn the lower court’s decision. After issuing a ruling in WWH, the 2016-2017 Roberts Court declined to hear challenges from other states with similarly overturned laws, leaving the laws struck down. In electing to hear June Medical Services v. Russo, the court has the opportunity to uphold or overturn the Fifth Circuit Court’s decision. However, today’s Supreme Court differs greatly from the Supreme Court in 2016.

In 2016, the court ruled 5-3 to overturn H.B. 2 in WWH shortly after the death of Justice Antonin Scalia. Scalia was replaced by Justice Neil Gorsuch, a Constitutional originalist who has never directly ruled on an abortion case.⁵ In 2018, Justice Anthony Kennedy, who authored the court’s majority opinion on Casey and was among the majority on WWH, retired, and was replaced by Justice Brett Kavanaugh. Kavanaugh has ruled once on the right to abortion in Garza v. Hargan in 2017, where he argued that precedent states that the government has “permissible interests in favoring fetal life…and refraining from facilitating abortion,” and that significant delay in care did not constitute undue burden.⁶ In regard to the 5-4 stay issued by the court in June Medical Services, Kavanaugh joined Gorsuch in voting to deny the application for stay, and was the only justice to issue an opinion alongside the ruling, arguing that because the doctors in question had not applied for and been denied admitting privileges since the WWH ruling, the case hinges on theoretical rather than demonstrable undue burden.⁷ Appointed by President Donald Trump, both Gorsuch and Kavanaugh are widely considered to be conservative judges, and while neither has a strong judicial record on abortion rights, both are anticipated to side with the conservative majority on the court.

The Supreme Court rarely overturns its own precedent, but concerns are high

The question of precedent will be central in SCOTUS hearing June Medical Services v. Russo so quickly after the WWH decision. Additionally, in hearing this case, the court will have the opportunity to reexamine all relevant precedent, including the Planned Parenthood of Southeastern Pennsylvania v. Casey decision and even Roe v. Wade. With a conservative court and an increasingly charged political environment, reproductive rights advocates fear that the June Medical Services v. Russo ruling may be the first step toward dismantling judicial protection of abortion rights in the United States.

If SCOTUS rules against June Medical Services, stating that admitting privileges do not cause an undue burden for women seeking to access abortion care, other states likely will introduce and enact similar legislation. These TRAP laws have the potential to limit or eliminate access to abortion for 25 million people of reproductive age. Numerous studies have demonstrated that limiting access to abortion care does not decrease the number of abortions but can result in patients using unsafe means to obtain an abortion.⁸

The medical community recognizes the danger of enacting restrictive legislation. The American College of Obstetricians and Gynecologists (ACOG), along with the American Medical Association, the Society of Maternal-Fetal Medicine, the Association for Sexual and Reproductive Medicine, the American Association of Family Practitioners, and many others, filed an amicus curiae in support of the June Medical Services plaintiffs.⁹ These brief filings are critical to ensuring the courts hear physician voices in this important legal decision, and ACOG’s briefs have been quoted in several previous Supreme Court opinions, concurrences, and dissents.
 

Action items

• Although June Medical Services v. Russo’s decision will not be made until early summer 2020, we can continue to use our voices and expertise to speak out against laws designed to limit access to abortion—at the state and federal levels. As women’s health clinicians, we see the impact abortion restrictions have on our patients, especially our low income and rural patients. Sharing these stories with our legislators, testifying for or against legislation, and speaking out in our communities can have a powerful impact. Check with your local ACOG chapter or with ACOG’s state and government affairs office for more information.
• Follow along with this case at SCOTUS Blog.
• Lastly, make sure you are registered to vote. We are in an election year, and using our voices in and out of the ballot box is critical. You can register here.

On March 4, 2020, the Supreme Court of the United States (SCOTUS) will hear opening arguments for June Medical Services v. Russo. (Please note that this case was originally referred to as June Medical Services v. Gee. However, Secretary Rebekah Gee resigned from her position on January 31, 2020, and was replaced by Interim Secretary Stephen Russo.) The case will examine a Louisiana law (Louisiana Act 620, or LA 620), originally passed in 2014, that requires physicians to have hospital admitting privileges within 30 miles of where they provide abortion services.¹ When LA 620 was signed into law in 2014, 5 of Louisiana’s 6 abortion clinics would not have met the standards created by this legislation and would have been forced to close, potentially leaving the vast majority of women in Louisiana without access to an abortion provider, and disproportionately impacting poor and rural women. Prior to enactment of this law, physicians at these 5 clinics attempted to obtain admitting privileges, and all were denied. The denials occurred due to two main reasons—because the providers admitted too few patients each year to qualify for hospital privileges or simply because they provided abortion care.² Shortly after this legislation was signed into law, the Center for Reproductive Rights (CRR) challenged the law, citing the undue burden it created for patients attempting to access abortion care.
 

Prior case also considered question of hospital privileges for abortion providers

Interestingly, SCOTUS already has ruled on this very question. In 1992, the Court ruled in Planned Parenthood of Southeastern Pennsylvania v. Casey that it is unconstitutional for a state to create an “undue burden” on a woman’s right to abortion prior to fetal viability.³ And in 2016, when considering whether or not requiring abortion providers to obtain hospital privileges creates an undue burden in Whole Women’s Health (WWH) v. Hellerstedt, the Supreme Court’s answer was yes, it does. WWH, with legal aid from CRR, challenged Texas House Bill 2 (H.B. 2), which similar to LA 620, required abortion providers to have local admitting privileges. Based largely on the precedent set in Casey, SCOTUS ruled 5-3 in favor of WWH.

The Louisiana law currently in question was written and challenged in district court simultaneous to the Supreme Court’s review of WWH. The district court declared LA 620 invalid and permanently enjoined its enforcement, finding the law would “drastically burden women’s right to choose abortions.”⁴ However, the US Court of Appeals for the Fifth Circuit reviewed the case and overturned the district court decision, finding the lower court’s analysis erroneous and stating, “no clinics will likely be forced to close on account of [LA 620].” The Fifth Circuit panel ruled that, despite the precedent of WWH, LA 620 did not create an undue burden because of state-level differences in admitting privileges, demographics, and geography. They also found that only 30% of the 2 million women living in Louisiana would be impacted by the law, predominantly via longer wait times, and argued that this does not represent significant burden. The plaintiffs filed for an emergency stay with SCOTUS, who granted the stay pending a full hearing. On March 4, the Supreme Court will hear arguments to determine if the Fifth Circuit was correct in drawing a distinction between LA 620 and the SCOTUS verdict in WWH.

Targeted restrictions on abortion providers

LA 620 joins a long series of laws meant to enact targeted restrictions on abortion providers, or “TRAP” laws. TRAP laws are written to limit access to abortion under the guise of improving patient safety, despite ample evidence to the contrary, and include such various regulations as admitting privileges, facilities requirements, waiting periods, and parental or partner notification. Many such laws have been enacted in the last decade, and many struck down based on judicial precedent.

How the Supreme Court has ruled in the past

When a case is appealed to the Supreme Court, the court can either decline to hear the case, thereby leaving the lower courts’ ruling in place, or choose to hear the case in full and either affirm or overturn the lower court’s decision. After issuing a ruling in WWH, the 2016-2017 Roberts Court declined to hear challenges from other states with similarly overturned laws, leaving the laws struck down. In electing to hear June Medical Services v. Russo, the court has the opportunity to uphold or overturn the Fifth Circuit Court’s decision. However, today’s Supreme Court differs greatly from the Supreme Court in 2016.

In 2016, the court ruled 5-3 to overturn H.B. 2 in WWH shortly after the death of Justice Antonin Scalia. Scalia was replaced by Justice Neil Gorsuch, a Constitutional originalist who has never directly ruled on an abortion case.⁵ In 2018, Justice Anthony Kennedy, who authored the court’s majority opinion on Casey and was among the majority on WWH, retired, and was replaced by Justice Brett Kavanaugh. Kavanaugh has ruled once on the right to abortion in Garza v. Hargan in 2017, where he argued that precedent states that the government has “permissible interests in favoring fetal life…and refraining from facilitating abortion,” and that significant delay in care did not constitute undue burden.⁶ In regard to the 5-4 stay issued by the court in June Medical Services, Kavanaugh joined Gorsuch in voting to deny the application for stay, and was the only justice to issue an opinion alongside the ruling, arguing that because the doctors in question had not applied for and been denied admitting privileges since the WWH ruling, the case hinges on theoretical rather than demonstrable undue burden.⁷ Appointed by President Donald Trump, both Gorsuch and Kavanaugh are widely considered to be conservative judges, and while neither has a strong judicial record on abortion rights, both are anticipated to side with the conservative majority on the court.

The Supreme Court rarely overturns its own precedent, but concerns are high

The question of precedent will be central in SCOTUS hearing June Medical Services v. Russo so quickly after the WWH decision. Additionally, in hearing this case, the court will have the opportunity to reexamine all relevant precedent, including the Planned Parenthood of Southeastern Pennsylvania v. Casey decision and even Roe v. Wade. With a conservative court and an increasingly charged political environment, reproductive rights advocates fear that the June Medical Services v. Russo ruling may be the first step toward dismantling judicial protection of abortion rights in the United States.

If SCOTUS rules against June Medical Services, stating that admitting privileges do not cause an undue burden for women seeking to access abortion care, other states likely will introduce and enact similar legislation. These TRAP laws have the potential to limit or eliminate access to abortion for 25 million people of reproductive age. Numerous studies have demonstrated that limiting access to abortion care does not decrease the number of abortions but can result in patients using unsafe means to obtain an abortion.⁸

The medical community recognizes the danger of enacting restrictive legislation. The American College of Obstetricians and Gynecologists (ACOG), along with the American Medical Association, the Society of Maternal-Fetal Medicine, the Association for Sexual and Reproductive Medicine, the American Association of Family Practitioners, and many others, filed an amicus curiae in support of the June Medical Services plaintiffs.⁹ These brief filings are critical to ensuring the courts hear physician voices in this important legal decision, and ACOG’s briefs have been quoted in several previous Supreme Court opinions, concurrences, and dissents.
 

Action items

• Although June Medical Services v. Russo’s decision will not be made until early summer 2020, we can continue to use our voices and expertise to speak out against laws designed to limit access to abortion—at the state and federal levels. As women’s health clinicians, we see the impact abortion restrictions have on our patients, especially our low income and rural patients. Sharing these stories with our legislators, testifying for or against legislation, and speaking out in our communities can have a powerful impact. Check with your local ACOG chapter or with ACOG’s state and government affairs office for more information.
• Follow along with this case at SCOTUS Blog.
• Lastly, make sure you are registered to vote. We are in an election year, and using our voices in and out of the ballot box is critical. You can register here.

On March 4, 2020, the Supreme Court of the United States (SCOTUS) will hear opening arguments for June Medical Services v. Russo. (Please note that this case was originally referred to as June Medical Services v. Gee. However, Secretary Rebekah Gee resigned from her position on January 31, 2020, and was replaced by Interim Secretary Stephen Russo.) The case will examine a Louisiana law (Louisiana Act 620, or LA 620), originally passed in 2014, that requires physicians to have hospital admitting privileges within 30 miles of where they provide abortion services.¹ When LA 620 was signed into law in 2014, 5 of Louisiana’s 6 abortion clinics would not have met the standards created by this legislation and would have been forced to close, potentially leaving the vast majority of women in Louisiana without access to an abortion provider, and disproportionately impacting poor and rural women. Prior to enactment of this law, physicians at these 5 clinics attempted to obtain admitting privileges, and all were denied. The denials occurred due to two main reasons—because the providers admitted too few patients each year to qualify for hospital privileges or simply because they provided abortion care.² Shortly after this legislation was signed into law, the Center for Reproductive Rights (CRR) challenged the law, citing the undue burden it created for patients attempting to access abortion care.
 

Prior case also considered question of hospital privileges for abortion providers

Interestingly, SCOTUS already has ruled on this very question. In 1992, the Court ruled in Planned Parenthood of Southeastern Pennsylvania v. Casey that it is unconstitutional for a state to create an “undue burden” on a woman’s right to abortion prior to fetal viability.³ And in 2016, when considering whether or not requiring abortion providers to obtain hospital privileges creates an undue burden in Whole Women’s Health (WWH) v. Hellerstedt, the Supreme Court’s answer was yes, it does. WWH, with legal aid from CRR, challenged Texas House Bill 2 (H.B. 2), which similar to LA 620, required abortion providers to have local admitting privileges. Based largely on the precedent set in Casey, SCOTUS ruled 5-3 in favor of WWH.

The Louisiana law currently in question was written and challenged in district court simultaneous to the Supreme Court’s review of WWH. The district court declared LA 620 invalid and permanently enjoined its enforcement, finding the law would “drastically burden women’s right to choose abortions.”⁴ However, the US Court of Appeals for the Fifth Circuit reviewed the case and overturned the district court decision, finding the lower court’s analysis erroneous and stating, “no clinics will likely be forced to close on account of [LA 620].” The Fifth Circuit panel ruled that, despite the precedent of WWH, LA 620 did not create an undue burden because of state-level differences in admitting privileges, demographics, and geography. They also found that only 30% of the 2 million women living in Louisiana would be impacted by the law, predominantly via longer wait times, and argued that this does not represent significant burden. The plaintiffs filed for an emergency stay with SCOTUS, who granted the stay pending a full hearing. On March 4, the Supreme Court will hear arguments to determine if the Fifth Circuit was correct in drawing a distinction between LA 620 and the SCOTUS verdict in WWH.

Targeted restrictions on abortion providers

LA 620 joins a long series of laws meant to enact targeted restrictions on abortion providers, or “TRAP” laws. TRAP laws are written to limit access to abortion under the guise of improving patient safety, despite ample evidence to the contrary, and include such various regulations as admitting privileges, facilities requirements, waiting periods, and parental or partner notification. Many such laws have been enacted in the last decade, and many struck down based on judicial precedent.

How the Supreme Court has ruled in the past

When a case is appealed to the Supreme Court, the court can either decline to hear the case, thereby leaving the lower courts’ ruling in place, or choose to hear the case in full and either affirm or overturn the lower court’s decision. After issuing a ruling in WWH, the 2016-2017 Roberts Court declined to hear challenges from other states with similarly overturned laws, leaving the laws struck down. In electing to hear June Medical Services v. Russo, the court has the opportunity to uphold or overturn the Fifth Circuit Court’s decision. However, today’s Supreme Court differs greatly from the Supreme Court in 2016.

In 2016, the court ruled 5-3 to overturn H.B. 2 in WWH shortly after the death of Justice Antonin Scalia. Scalia was replaced by Justice Neil Gorsuch, a Constitutional originalist who has never directly ruled on an abortion case.⁵ In 2018, Justice Anthony Kennedy, who authored the court’s majority opinion on Casey and was among the majority on WWH, retired, and was replaced by Justice Brett Kavanaugh. Kavanaugh has ruled once on the right to abortion in Garza v. Hargan in 2017, where he argued that precedent states that the government has “permissible interests in favoring fetal life…and refraining from facilitating abortion,” and that significant delay in care did not constitute undue burden.⁶ In regard to the 5-4 stay issued by the court in June Medical Services, Kavanaugh joined Gorsuch in voting to deny the application for stay, and was the only justice to issue an opinion alongside the ruling, arguing that because the doctors in question had not applied for and been denied admitting privileges since the WWH ruling, the case hinges on theoretical rather than demonstrable undue burden.⁷ Appointed by President Donald Trump, both Gorsuch and Kavanaugh are widely considered to be conservative judges, and while neither has a strong judicial record on abortion rights, both are anticipated to side with the conservative majority on the court.

The Supreme Court rarely overturns its own precedent, but concerns are high

The question of precedent will be central in SCOTUS hearing June Medical Services v. Russo so quickly after the WWH decision. Additionally, in hearing this case, the court will have the opportunity to reexamine all relevant precedent, including the Planned Parenthood of Southeastern Pennsylvania v. Casey decision and even Roe v. Wade. With a conservative court and an increasingly charged political environment, reproductive rights advocates fear that the June Medical Services v. Russo ruling may be the first step toward dismantling judicial protection of abortion rights in the United States.

If SCOTUS rules against June Medical Services, stating that admitting privileges do not cause an undue burden for women seeking to access abortion care, other states likely will introduce and enact similar legislation. These TRAP laws have the potential to limit or eliminate access to abortion for 25 million people of reproductive age. Numerous studies have demonstrated that limiting access to abortion care does not decrease the number of abortions but can result in patients using unsafe means to obtain an abortion.⁸

The medical community recognizes the danger of enacting restrictive legislation. The American College of Obstetricians and Gynecologists (ACOG), along with the American Medical Association, the Society of Maternal-Fetal Medicine, the Association for Sexual and Reproductive Medicine, the American Association of Family Practitioners, and many others, filed an amicus curiae in support of the June Medical Services plaintiffs.⁹ These brief filings are critical to ensuring the courts hear physician voices in this important legal decision, and ACOG’s briefs have been quoted in several previous Supreme Court opinions, concurrences, and dissents.
 

Action items

• Although June Medical Services v. Russo’s decision will not be made until early summer 2020, we can continue to use our voices and expertise to speak out against laws designed to limit access to abortion—at the state and federal levels. As women’s health clinicians, we see the impact abortion restrictions have on our patients, especially our low income and rural patients. Sharing these stories with our legislators, testifying for or against legislation, and speaking out in our communities can have a powerful impact. Check with your local ACOG chapter or with ACOG’s state and government affairs office for more information.
• Follow along with this case at SCOTUS Blog.
• Lastly, make sure you are registered to vote. We are in an election year, and using our voices in and out of the ballot box is critical. You can register here.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

ORLANDO – Knowledge of vaping devices, familiarity with terminology, and the ability to quickly pinpoint individuals at risk of lung injury are just a few skills that can help critical care professionals confronted with patients who may have vaping-associated lung disease, according to a new guidance document.

Andrew D. Bowser/MDedge News

The guidance offers a risk-stratification system that classifies patients into groups based on exposure, symptoms, and imaging results, and provides specific evaluation needs and management strategies for each. The guidance is designed to help critical care professionals efficiently identify those at high risk of respiratory failure.

Physicians also need to communicate with patients to identify what substances are being vaped and develop effective methods to encourage abstinence, according to the authors, led by Craig M. Lilly, MD, FCCP, professor of medicine, anesthesiology, and surgery at the University of Massachusetts, Worcester.

“I would encourage every intensivist, when they leave their intensive care unit at night, [to ask], ‘have I advised against vaping today?’ ” Dr. Lilly said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The guidelines, concurrently published as a review article in Critical Care Explorations, propose the term vaping-associated respiratory distress syndrome (VARDS), which the authors say constitutes an acute and progressive respiratory syndrome marked by pathologic changes of lung injury and potentially life-threatening hypoxemic respiratory failure.

They also introduce the three-group Worcester classification system, which is intended to triage vaping-exposed individuals for risk of VARDS based on the presence or absence of vaping-related symptoms and infiltrates, and normal or abnormal oxygen saturation.

“It’s very simple,” said Dr. Lilly, who added that the risk stratification model was developed at the request of Massachusetts public health officials.

Patients with vaping exposure but no symptoms attributable to vaping, such as cough, chest pain, or weight loss, are classified as Worcester Low Risk and testing is not recommended, he said.

By contrast, individuals are considered Worcester Medium Risk if they have vaping exposure, symptoms, and a vaping-associated abnormal pattern on imaging, but no hypoxemia; the presence of hypoxemia would tip the scale toward Worcester High Risk.

“Most patients that have died from vaping have been sent out of emergency rooms when they were noted to be hypoxic,” Dr. Lilly told meeting attendees.

ORLANDO – Knowledge of vaping devices, familiarity with terminology, and the ability to quickly pinpoint individuals at risk of lung injury are just a few skills that can help critical care professionals confronted with patients who may have vaping-associated lung disease, according to a new guidance document.

Andrew D. Bowser/MDedge News

The guidance offers a risk-stratification system that classifies patients into groups based on exposure, symptoms, and imaging results, and provides specific evaluation needs and management strategies for each. The guidance is designed to help critical care professionals efficiently identify those at high risk of respiratory failure.

Physicians also need to communicate with patients to identify what substances are being vaped and develop effective methods to encourage abstinence, according to the authors, led by Craig M. Lilly, MD, FCCP, professor of medicine, anesthesiology, and surgery at the University of Massachusetts, Worcester.

“I would encourage every intensivist, when they leave their intensive care unit at night, [to ask], ‘have I advised against vaping today?’ ” Dr. Lilly said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The guidelines, concurrently published as a review article in Critical Care Explorations, propose the term vaping-associated respiratory distress syndrome (VARDS), which the authors say constitutes an acute and progressive respiratory syndrome marked by pathologic changes of lung injury and potentially life-threatening hypoxemic respiratory failure.

They also introduce the three-group Worcester classification system, which is intended to triage vaping-exposed individuals for risk of VARDS based on the presence or absence of vaping-related symptoms and infiltrates, and normal or abnormal oxygen saturation.

“It’s very simple,” said Dr. Lilly, who added that the risk stratification model was developed at the request of Massachusetts public health officials.

Patients with vaping exposure but no symptoms attributable to vaping, such as cough, chest pain, or weight loss, are classified as Worcester Low Risk and testing is not recommended, he said.

By contrast, individuals are considered Worcester Medium Risk if they have vaping exposure, symptoms, and a vaping-associated abnormal pattern on imaging, but no hypoxemia; the presence of hypoxemia would tip the scale toward Worcester High Risk.

“Most patients that have died from vaping have been sent out of emergency rooms when they were noted to be hypoxic,” Dr. Lilly told meeting attendees.

ORLANDO – Knowledge of vaping devices, familiarity with terminology, and the ability to quickly pinpoint individuals at risk of lung injury are just a few skills that can help critical care professionals confronted with patients who may have vaping-associated lung disease, according to a new guidance document.

Andrew D. Bowser/MDedge News

The guidance offers a risk-stratification system that classifies patients into groups based on exposure, symptoms, and imaging results, and provides specific evaluation needs and management strategies for each. The guidance is designed to help critical care professionals efficiently identify those at high risk of respiratory failure.

Physicians also need to communicate with patients to identify what substances are being vaped and develop effective methods to encourage abstinence, according to the authors, led by Craig M. Lilly, MD, FCCP, professor of medicine, anesthesiology, and surgery at the University of Massachusetts, Worcester.

“I would encourage every intensivist, when they leave their intensive care unit at night, [to ask], ‘have I advised against vaping today?’ ” Dr. Lilly said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The guidelines, concurrently published as a review article in Critical Care Explorations, propose the term vaping-associated respiratory distress syndrome (VARDS), which the authors say constitutes an acute and progressive respiratory syndrome marked by pathologic changes of lung injury and potentially life-threatening hypoxemic respiratory failure.

They also introduce the three-group Worcester classification system, which is intended to triage vaping-exposed individuals for risk of VARDS based on the presence or absence of vaping-related symptoms and infiltrates, and normal or abnormal oxygen saturation.

“It’s very simple,” said Dr. Lilly, who added that the risk stratification model was developed at the request of Massachusetts public health officials.

Patients with vaping exposure but no symptoms attributable to vaping, such as cough, chest pain, or weight loss, are classified as Worcester Low Risk and testing is not recommended, he said.

By contrast, individuals are considered Worcester Medium Risk if they have vaping exposure, symptoms, and a vaping-associated abnormal pattern on imaging, but no hypoxemia; the presence of hypoxemia would tip the scale toward Worcester High Risk.

“Most patients that have died from vaping have been sent out of emergency rooms when they were noted to be hypoxic,” Dr. Lilly told meeting attendees.