John E. Parker, MD, was working at a West Virginia hospital in 2015 when a 31-year-old female patient was admitted with acute respiratory problems. A team of doctors ultimately suspected that her mysterious case of lipoid pneumonia might be related to vaping and weren’t sure they had seen anything like it before. They were intrigued enough to submit the case for presentation at the CHEST Annual Meeting that year (Chest. 2015;148:382A. doi: 10.1378/chest.2274860).

Now, almost 4 years later, federal officials have begun investigating a national outbreak of severe lung illnesses linked to vaping that has struck more than 150 patients in 16 states. In an interview, Dr. Parker, a professor of pulmonary critical care and sleep medicine at West Virginia University, Morgantown, described what happened.
 

Q: Can you describe what the patient’s symptoms were when she arrived?

We would view them as classic for what is getting to be called vaping-associated lung disease. She was very, very short of breath and had a cough, and we were, of course, very worried that she might have pneumonia or some other acute respiratory illness. And then she was so sick she needed to be intubated.

Q: What happens next in cases like this?

We look for things like a [hemorrhage] or an active infection. And then for lipid-containing macrophages. And then we usually start some antibiotics [and a] low-dose steroid and then support the patient with a ventilator and oxygen and nutrition. And then just kind of wait and see if any other cultures come back to prove anything different than what you might be thinking.

Early on, we just felt like it was an unusual case and may not be a common viral or bacterial infection.
 

Q: How did you figure out the cause of her lipoid pneumonia was e-cigarettes?

It’s a diagnosis of exclusion. We excluded other [options], and it became the most likely cause.

We were convinced enough that the case was submitted for [presentation at the CHEST annual meeting] and was accepted.
 

Q: Once you figured out the cause could be e-cigarettes, did you contact the Centers for Disease Control and Prevention or the Food and Drug Administration or any other regulatory agency to tell them about this?

We did not. We felt at the time that putting it in the medical literature was appropriate. And if other case reports from other parts of the country came forward, then we’d have more of a clustering of findings that might then warrant research agencies [getting a] better understanding [about] the cause of the disease.

Q: Which federal agency would you report it to, if you did?

In 2015, the FDA, of course, was still regulating cigarettes, but I don’t think the government had yet decided who would regulate vaping products. So I’m sure it was unclear who we should call.

Q: So did you or your team think this was a one-off event when you witnessed it?

We really felt that it wasn’t going to be a one-off event and that it was what we usually called in public health a “sentinel” health event … that it was an example of a respiratory illness that can be caused by this exposure and that it probably wasn’t the first case ever seen nor would it be the last.

Q: Was it the first case that you had seen at your institution?

To our knowledge it was our first case, but we are humble enough clinicians to realize we may have missed some other cases that we interpreted [as] viral pneumonia or bacterial pneumonia.

Q: Have you seen more cases since then?

I know we’ve seen a case [of alveolar hemorrhage syndrome] that we published, and in polling some colleagues, we think we’ve probably also seen [cases of] cryptogenic organizing pneumonia as well as lipoid pneumonia and acute eosinophilic pneumonia. Yeah, we’ve certainly seen at least probably four forms of lung disease from vaping.

Q: If your team was seeing this back in 2015, is it possible that it’s been happening in the four years since then and people just don’t know about it?

I really have every reason to think we were not the first ones to see it, by any means.

And I don’t think we were even the first ones to report it. I think that there were some clusters in Wisconsin and some other places in the United States. I also know that the Japanese have been very interested. They’ve probably got four or five papers at least in the medical literature about vaping-related lung injury.
 

Q: Do you have a theory of what might be causing the lipoid pneumonia cases? Do you think there may be certain chemicals that are irritants?

We need a strong multidisciplinary team to understand the real etiology and cause of lung injury from inhalation. I think it could be any number of components in the mixtures. Lungs don’t like oil, in general, and probably the most specific agent that’s been studied recently is diacetyl, which was studied in popcorn-flavoring lung disease.

Q: Have these kinds of cases changed the way you approach patients?

Yeah, we search very carefully for a history of vaping. … I think it’s quite important to understand if they might be using inhaled agents or vaping that might present new toxicities to the lung.

Q: Will these illnesses have long-term health effects?

An inhalational injury may cause an acute lung injury that’s life-threatening and that someone may survive from and have no long-term sequelae [condition]. But there also is the possibility that long-term [e-cigarette] use may cause more insidious or chronic diseases from which there may not be a full recovery.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

John E. Parker, MD, was working at a West Virginia hospital in 2015 when a 31-year-old female patient was admitted with acute respiratory problems. A team of doctors ultimately suspected that her mysterious case of lipoid pneumonia might be related to vaping and weren’t sure they had seen anything like it before. They were intrigued enough to submit the case for presentation at the CHEST Annual Meeting that year (Chest. 2015;148:382A. doi: 10.1378/chest.2274860).

Now, almost 4 years later, federal officials have begun investigating a national outbreak of severe lung illnesses linked to vaping that has struck more than 150 patients in 16 states. In an interview, Dr. Parker, a professor of pulmonary critical care and sleep medicine at West Virginia University, Morgantown, described what happened.
 

Q: Can you describe what the patient’s symptoms were when she arrived?

We would view them as classic for what is getting to be called vaping-associated lung disease. She was very, very short of breath and had a cough, and we were, of course, very worried that she might have pneumonia or some other acute respiratory illness. And then she was so sick she needed to be intubated.

Q: What happens next in cases like this?

We look for things like a [hemorrhage] or an active infection. And then for lipid-containing macrophages. And then we usually start some antibiotics [and a] low-dose steroid and then support the patient with a ventilator and oxygen and nutrition. And then just kind of wait and see if any other cultures come back to prove anything different than what you might be thinking.

Early on, we just felt like it was an unusual case and may not be a common viral or bacterial infection.
 

Q: How did you figure out the cause of her lipoid pneumonia was e-cigarettes?

It’s a diagnosis of exclusion. We excluded other [options], and it became the most likely cause.

We were convinced enough that the case was submitted for [presentation at the CHEST annual meeting] and was accepted.
 

Q: Once you figured out the cause could be e-cigarettes, did you contact the Centers for Disease Control and Prevention or the Food and Drug Administration or any other regulatory agency to tell them about this?

We did not. We felt at the time that putting it in the medical literature was appropriate. And if other case reports from other parts of the country came forward, then we’d have more of a clustering of findings that might then warrant research agencies [getting a] better understanding [about] the cause of the disease.

Q: Which federal agency would you report it to, if you did?

In 2015, the FDA, of course, was still regulating cigarettes, but I don’t think the government had yet decided who would regulate vaping products. So I’m sure it was unclear who we should call.

Q: So did you or your team think this was a one-off event when you witnessed it?

We really felt that it wasn’t going to be a one-off event and that it was what we usually called in public health a “sentinel” health event … that it was an example of a respiratory illness that can be caused by this exposure and that it probably wasn’t the first case ever seen nor would it be the last.

Q: Was it the first case that you had seen at your institution?

To our knowledge it was our first case, but we are humble enough clinicians to realize we may have missed some other cases that we interpreted [as] viral pneumonia or bacterial pneumonia.

Q: Have you seen more cases since then?

I know we’ve seen a case [of alveolar hemorrhage syndrome] that we published, and in polling some colleagues, we think we’ve probably also seen [cases of] cryptogenic organizing pneumonia as well as lipoid pneumonia and acute eosinophilic pneumonia. Yeah, we’ve certainly seen at least probably four forms of lung disease from vaping.

Q: If your team was seeing this back in 2015, is it possible that it’s been happening in the four years since then and people just don’t know about it?

I really have every reason to think we were not the first ones to see it, by any means.

And I don’t think we were even the first ones to report it. I think that there were some clusters in Wisconsin and some other places in the United States. I also know that the Japanese have been very interested. They’ve probably got four or five papers at least in the medical literature about vaping-related lung injury.
 

Q: Do you have a theory of what might be causing the lipoid pneumonia cases? Do you think there may be certain chemicals that are irritants?

We need a strong multidisciplinary team to understand the real etiology and cause of lung injury from inhalation. I think it could be any number of components in the mixtures. Lungs don’t like oil, in general, and probably the most specific agent that’s been studied recently is diacetyl, which was studied in popcorn-flavoring lung disease.

Q: Have these kinds of cases changed the way you approach patients?

Yeah, we search very carefully for a history of vaping. … I think it’s quite important to understand if they might be using inhaled agents or vaping that might present new toxicities to the lung.

Q: Will these illnesses have long-term health effects?

An inhalational injury may cause an acute lung injury that’s life-threatening and that someone may survive from and have no long-term sequelae [condition]. But there also is the possibility that long-term [e-cigarette] use may cause more insidious or chronic diseases from which there may not be a full recovery.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

John E. Parker, MD, was working at a West Virginia hospital in 2015 when a 31-year-old female patient was admitted with acute respiratory problems. A team of doctors ultimately suspected that her mysterious case of lipoid pneumonia might be related to vaping and weren’t sure they had seen anything like it before. They were intrigued enough to submit the case for presentation at the CHEST Annual Meeting that year (Chest. 2015;148:382A. doi: 10.1378/chest.2274860).

Now, almost 4 years later, federal officials have begun investigating a national outbreak of severe lung illnesses linked to vaping that has struck more than 150 patients in 16 states. In an interview, Dr. Parker, a professor of pulmonary critical care and sleep medicine at West Virginia University, Morgantown, described what happened.
 

Q: Can you describe what the patient’s symptoms were when she arrived?

We would view them as classic for what is getting to be called vaping-associated lung disease. She was very, very short of breath and had a cough, and we were, of course, very worried that she might have pneumonia or some other acute respiratory illness. And then she was so sick she needed to be intubated.

Q: What happens next in cases like this?

We look for things like a [hemorrhage] or an active infection. And then for lipid-containing macrophages. And then we usually start some antibiotics [and a] low-dose steroid and then support the patient with a ventilator and oxygen and nutrition. And then just kind of wait and see if any other cultures come back to prove anything different than what you might be thinking.

Early on, we just felt like it was an unusual case and may not be a common viral or bacterial infection.
 

Q: How did you figure out the cause of her lipoid pneumonia was e-cigarettes?

It’s a diagnosis of exclusion. We excluded other [options], and it became the most likely cause.

We were convinced enough that the case was submitted for [presentation at the CHEST annual meeting] and was accepted.
 

Q: Once you figured out the cause could be e-cigarettes, did you contact the Centers for Disease Control and Prevention or the Food and Drug Administration or any other regulatory agency to tell them about this?

We did not. We felt at the time that putting it in the medical literature was appropriate. And if other case reports from other parts of the country came forward, then we’d have more of a clustering of findings that might then warrant research agencies [getting a] better understanding [about] the cause of the disease.

Q: Which federal agency would you report it to, if you did?

In 2015, the FDA, of course, was still regulating cigarettes, but I don’t think the government had yet decided who would regulate vaping products. So I’m sure it was unclear who we should call.

Q: So did you or your team think this was a one-off event when you witnessed it?

We really felt that it wasn’t going to be a one-off event and that it was what we usually called in public health a “sentinel” health event … that it was an example of a respiratory illness that can be caused by this exposure and that it probably wasn’t the first case ever seen nor would it be the last.

Q: Was it the first case that you had seen at your institution?

To our knowledge it was our first case, but we are humble enough clinicians to realize we may have missed some other cases that we interpreted [as] viral pneumonia or bacterial pneumonia.

Q: Have you seen more cases since then?

I know we’ve seen a case [of alveolar hemorrhage syndrome] that we published, and in polling some colleagues, we think we’ve probably also seen [cases of] cryptogenic organizing pneumonia as well as lipoid pneumonia and acute eosinophilic pneumonia. Yeah, we’ve certainly seen at least probably four forms of lung disease from vaping.

Q: If your team was seeing this back in 2015, is it possible that it’s been happening in the four years since then and people just don’t know about it?

I really have every reason to think we were not the first ones to see it, by any means.

And I don’t think we were even the first ones to report it. I think that there were some clusters in Wisconsin and some other places in the United States. I also know that the Japanese have been very interested. They’ve probably got four or five papers at least in the medical literature about vaping-related lung injury.
 

Q: Do you have a theory of what might be causing the lipoid pneumonia cases? Do you think there may be certain chemicals that are irritants?

We need a strong multidisciplinary team to understand the real etiology and cause of lung injury from inhalation. I think it could be any number of components in the mixtures. Lungs don’t like oil, in general, and probably the most specific agent that’s been studied recently is diacetyl, which was studied in popcorn-flavoring lung disease.

Q: Have these kinds of cases changed the way you approach patients?

Yeah, we search very carefully for a history of vaping. … I think it’s quite important to understand if they might be using inhaled agents or vaping that might present new toxicities to the lung.

Q: Will these illnesses have long-term health effects?

An inhalational injury may cause an acute lung injury that’s life-threatening and that someone may survive from and have no long-term sequelae [condition]. But there also is the possibility that long-term [e-cigarette] use may cause more insidious or chronic diseases from which there may not be a full recovery.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab can induce lipodystrophy with severe metabolic complications, according to a case study.

A 47-year-old woman received pembrolizumab to treat metastatic melanoma and developed immune-related generalized acquired lipodystrophy. The condition has persisted 12 months after she stopped taking pembrolizumab.

Julie Delyon, MD, PhD, of Saint-Louis Hospital in Paris, and colleagues described this case in the British Journal of Dermatology.

The patient was diagnosed with BRAF-mutated, stage IV melanoma with bone and lymph node metastases. She received pembrolizumab at 2 mg/kg every 3 weeks as first-line treatment. She achieved a complete response and was still in remission at last follow-up.

The patient was obese at baseline, with a body mass index of 40 kg/m², but she did not have diabetes, hepatic steatosis, or dyslipidemia.

Within 2 months of starting pembrolizumab, the patient observed “some major changes to her physical appearance,” according to Dr. Delyon and colleagues. At 10 months, the patient had severe lipodystrophy.

The patient experienced a change in fat distribution – namely, severe peripheral lipoatrophy and an accumulation of trunk fat. Imaging revealed a decrease in subcutaneous adipose tissue, which contrasted with an increase in visceral fat observed from baseline.

The patient also developed “moderate hirsutism, facial and limb atrophy, and prominent forearm and leg muscles and veins,” according to the authors. She had impaired glucose tolerance with insulin resistance, reduced concentrations of leptin and adiponectin, hypertriglyceridemia, a low level of HDL cholesterol, and hepatic steatosis.

Analyses of subcutaneous fat revealed adipose tissue atrophy with edema, lipophages, and CD3+/CD4+ T-cell infiltration of the fat and vessel walls. This suggested that the lipodystrophy had an autoimmune origin, according to the authors.

The patient had no family history of autoimmune disease or lipodystrophy. She tested negative for mutations in 23 genes associated with generalized lipodystrophy.

The patient also tested negative for HIV, antinuclear antibodies, native anti-DNA, and anti-insulin receptor antibodies. There were no signs of panniculitis, and the authors noted that “there were no arguments in favor of hyperthyroidism, Cushing syndrome, or acromegaly.”

In an attempt to reverse the lipodystrophy, the researchers stopped pembrolizumab treatment. The patient was treated for diabetes and hypertriglyceridemia as well. She could not receive corticosteroids because of the risk of severe metabolic complications, and she didn’t receive metreleptin because it wasn’t available. The patient still had lipodystrophy 12 months after stopping pembrolizumab.

Dr. Delyon and colleagues wrote that this case suggests pembrolizumab, and perhaps other anti–programmed death 1 therapies, may cause lipodystrophy with severe metabolic complications. “The long-term side effects of such metabolic adverse events, although rare, are unknown and will probably become a topic of utmost importance, considering the increasing rate of remission following ICIs and their use in the adjuvant setting.”

Two coauthors reported relationships with Merck, which markets pembrolizumab as Keytruda. The authors also reported relationships with Bristol-Myers Squibb, Pierre Fabre, Takeda, Innate Pharma, LEO Pharma, Roche, GlaxoSmithKline, Novartis, and Amgen.

jensmith@mdedge.com

SOURCE: Delyon J et al. Br J Dermatol. 2019 May 11. doi: 10.1111/bjd.18124.

Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab can induce lipodystrophy with severe metabolic complications, according to a case study.

A 47-year-old woman received pembrolizumab to treat metastatic melanoma and developed immune-related generalized acquired lipodystrophy. The condition has persisted 12 months after she stopped taking pembrolizumab.

Julie Delyon, MD, PhD, of Saint-Louis Hospital in Paris, and colleagues described this case in the British Journal of Dermatology.

The patient was diagnosed with BRAF-mutated, stage IV melanoma with bone and lymph node metastases. She received pembrolizumab at 2 mg/kg every 3 weeks as first-line treatment. She achieved a complete response and was still in remission at last follow-up.

The patient was obese at baseline, with a body mass index of 40 kg/m², but she did not have diabetes, hepatic steatosis, or dyslipidemia.

Within 2 months of starting pembrolizumab, the patient observed “some major changes to her physical appearance,” according to Dr. Delyon and colleagues. At 10 months, the patient had severe lipodystrophy.

The patient experienced a change in fat distribution – namely, severe peripheral lipoatrophy and an accumulation of trunk fat. Imaging revealed a decrease in subcutaneous adipose tissue, which contrasted with an increase in visceral fat observed from baseline.

The patient also developed “moderate hirsutism, facial and limb atrophy, and prominent forearm and leg muscles and veins,” according to the authors. She had impaired glucose tolerance with insulin resistance, reduced concentrations of leptin and adiponectin, hypertriglyceridemia, a low level of HDL cholesterol, and hepatic steatosis.

Analyses of subcutaneous fat revealed adipose tissue atrophy with edema, lipophages, and CD3+/CD4+ T-cell infiltration of the fat and vessel walls. This suggested that the lipodystrophy had an autoimmune origin, according to the authors.

The patient had no family history of autoimmune disease or lipodystrophy. She tested negative for mutations in 23 genes associated with generalized lipodystrophy.

The patient also tested negative for HIV, antinuclear antibodies, native anti-DNA, and anti-insulin receptor antibodies. There were no signs of panniculitis, and the authors noted that “there were no arguments in favor of hyperthyroidism, Cushing syndrome, or acromegaly.”

In an attempt to reverse the lipodystrophy, the researchers stopped pembrolizumab treatment. The patient was treated for diabetes and hypertriglyceridemia as well. She could not receive corticosteroids because of the risk of severe metabolic complications, and she didn’t receive metreleptin because it wasn’t available. The patient still had lipodystrophy 12 months after stopping pembrolizumab.

Dr. Delyon and colleagues wrote that this case suggests pembrolizumab, and perhaps other anti–programmed death 1 therapies, may cause lipodystrophy with severe metabolic complications. “The long-term side effects of such metabolic adverse events, although rare, are unknown and will probably become a topic of utmost importance, considering the increasing rate of remission following ICIs and their use in the adjuvant setting.”

Two coauthors reported relationships with Merck, which markets pembrolizumab as Keytruda. The authors also reported relationships with Bristol-Myers Squibb, Pierre Fabre, Takeda, Innate Pharma, LEO Pharma, Roche, GlaxoSmithKline, Novartis, and Amgen.

jensmith@mdedge.com

SOURCE: Delyon J et al. Br J Dermatol. 2019 May 11. doi: 10.1111/bjd.18124.

Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab can induce lipodystrophy with severe metabolic complications, according to a case study.

A 47-year-old woman received pembrolizumab to treat metastatic melanoma and developed immune-related generalized acquired lipodystrophy. The condition has persisted 12 months after she stopped taking pembrolizumab.

Julie Delyon, MD, PhD, of Saint-Louis Hospital in Paris, and colleagues described this case in the British Journal of Dermatology.

The patient was diagnosed with BRAF-mutated, stage IV melanoma with bone and lymph node metastases. She received pembrolizumab at 2 mg/kg every 3 weeks as first-line treatment. She achieved a complete response and was still in remission at last follow-up.

The patient was obese at baseline, with a body mass index of 40 kg/m², but she did not have diabetes, hepatic steatosis, or dyslipidemia.

Within 2 months of starting pembrolizumab, the patient observed “some major changes to her physical appearance,” according to Dr. Delyon and colleagues. At 10 months, the patient had severe lipodystrophy.

The patient experienced a change in fat distribution – namely, severe peripheral lipoatrophy and an accumulation of trunk fat. Imaging revealed a decrease in subcutaneous adipose tissue, which contrasted with an increase in visceral fat observed from baseline.

The patient also developed “moderate hirsutism, facial and limb atrophy, and prominent forearm and leg muscles and veins,” according to the authors. She had impaired glucose tolerance with insulin resistance, reduced concentrations of leptin and adiponectin, hypertriglyceridemia, a low level of HDL cholesterol, and hepatic steatosis.

Analyses of subcutaneous fat revealed adipose tissue atrophy with edema, lipophages, and CD3+/CD4+ T-cell infiltration of the fat and vessel walls. This suggested that the lipodystrophy had an autoimmune origin, according to the authors.

The patient had no family history of autoimmune disease or lipodystrophy. She tested negative for mutations in 23 genes associated with generalized lipodystrophy.

The patient also tested negative for HIV, antinuclear antibodies, native anti-DNA, and anti-insulin receptor antibodies. There were no signs of panniculitis, and the authors noted that “there were no arguments in favor of hyperthyroidism, Cushing syndrome, or acromegaly.”

In an attempt to reverse the lipodystrophy, the researchers stopped pembrolizumab treatment. The patient was treated for diabetes and hypertriglyceridemia as well. She could not receive corticosteroids because of the risk of severe metabolic complications, and she didn’t receive metreleptin because it wasn’t available. The patient still had lipodystrophy 12 months after stopping pembrolizumab.

Dr. Delyon and colleagues wrote that this case suggests pembrolizumab, and perhaps other anti–programmed death 1 therapies, may cause lipodystrophy with severe metabolic complications. “The long-term side effects of such metabolic adverse events, although rare, are unknown and will probably become a topic of utmost importance, considering the increasing rate of remission following ICIs and their use in the adjuvant setting.”

Two coauthors reported relationships with Merck, which markets pembrolizumab as Keytruda. The authors also reported relationships with Bristol-Myers Squibb, Pierre Fabre, Takeda, Innate Pharma, LEO Pharma, Roche, GlaxoSmithKline, Novartis, and Amgen.

jensmith@mdedge.com

SOURCE: Delyon J et al. Br J Dermatol. 2019 May 11. doi: 10.1111/bjd.18124.

Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q2. Correct Answer: A  
 
Rationale:  
In a patient with chronic pancreatitis and a pancreatic mass, the most likely etiology is adenocarcinoma. This patient has radiologically resectable pancreas cancer. There is no evidence of lymphadenopathy or vascular invasion. Performing an ERCP with stent placement to relieve biliary obstruction has not been shown to be of benefit in patients with a resectable pancreatic mass. In fact, surgical outcomes are worse if a stent is placed in the bile duct. Surgical consultation should be obtained and the patient should undergo pancreaticoduodenectomy. EUS is sometimes done, but most cases of resectable disease should go straight to surgery.  
 
Reference  
Ghaneh P, et al. Biology and management of pancreatic cancer. Gut 2007;56(8)1134-52. 
 
ginews@gastro.org

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Q1. Correct Answer: B  
 
Rationale:  
Risk factors for gallstone formation include increased age, female gender, pregnancy, dyslipidemia, diabetes, obesity and rapid weight loss - especially after gastric bypass surgery. Medications such as hormone replacement therapies/ oral contraceptive agents, fibrates, somatostatin analogues also increase gallstone risk. Currently, there is evidence suggesting potential benefit of prophylactic cholecystectomy during Roux-en-Y gastric bypass, given the potential risk of gallstone formation with rapid weight loss following surgery. However, there is also data from randomized controlled trials that the use of ursodeoxycholic acid following surgery may help reduce risk of gallstone formation for this group of patients.  
 
Reference: 
Stokes et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder Stones during weight loss: A meta-analysis of randomized controlled trials. 2014. Clin Gastroenterol Hepatol. 2014;12:1090-100. 

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

Adding local treatment to systemic therapy may extend survival among certain patients with oligometastatic non–small cell lung cancer (NSCLC), according to a retrospective look at more than 34,000 patients.

Surgical resection provided the greatest survival benefit, followed by external beam radiotherapy or thermal ablation (EBRT/TA), reported lead author Johannes Uhlig, MD, of University Medical Center Göttingen (Germany) and colleagues.

NSCLC patients with five or fewer metastatic sites (oligometastatic disease) are thought to achieve better outcomes than patients with more widely disseminated disease, the investigators noted in JAMA Network Open, but the benefit of local therapy for this population is unclear.

“A recent randomized, prospective study of 74 patients with oligometastatic NSCLC identified superior progression-free survival with local control after hypofractionated radiotherapy or surgical resection and radiotherapy compared with systemic therapy alone, suggesting an important application of local treatment options for patients with metastatic disease,” the investigators wrote.

To build on these findings, the investigators retrospectively evaluated 34,887 patients with stage IV NSCLC who had up to one distant metastatic lesion in the liver, lung, brain, or bone, as documented in the National Cancer Database. Treatment groups were divided into patients who received systemic therapy alone, surgical resection plus systemic therapy, or EBRT/TA plus systemic therapy. Multivariable Cox proportional hazards models were used to compare overall survival among the three groups.

Including a median follow-up of 39.4 months, data analysis showed that patients who underwent surgery and systemic therapy fared the best. Adding surgery reduced mortality risk by 38% and 41%, compared with EBRT/TA plus systemic therapy and systemic therapy alone, respectively (P less than .001 for both). Compared with systemic therapy alone, adding EBRT/TA reduced mortality risk by 5% (P = .002).

The impact of EBRT/TA varied among subgroups. For those with squamous cell carcinoma who had limited nodal disease, adding EBRT/TA resulted in a clear benefit, reducing mortality risk by 32% (P less than .001). Compared with systemic therapy alone, this benefit translated to higher survival rates for up to 3 years. Conversely, adding EBRT/TA increased risk of death by 39% among patients with extended local and distant adenocarcinoma (P less than .001). In this subgroup, survival rates over the next 3 years were higher among patients treated with systemic therapy alone.

“The present study supports a combined approach of local therapy in addition to systemic treatment for select patients with oligometastatic NSCLC,” the investigators concluded.

The study was funded by the U.S. Department of Defense. The investigators disclosed additional relationships with Bayer, AstraZeneca, Bristol-Myers Squibb, and others.

SOURCE: Uhlig et al. JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702.

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

BANGKOK – Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

bjancin@mdedge.com

SOURCE: Kay L et al. IEC 2019, Abstract P029.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.

NEW YORK – Progress in understanding the sequence of events that drives vitiligo is not only behind highly promising new options for treatment, but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.

MarijaRadovic/Getty Images

Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.

In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.

As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.

“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.

However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.

These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.

In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.

This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.

Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.

“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.

In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.

Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.

It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.

“Based on these data, we are expecting clinical trials soon,” he said.

Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.