SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.

A literature review has failed to provide new insights regarding the burden of mild hemophilia A.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

In the 17 studies reviewed, mean annual bleeding rates (ABRs) were largely unreported. Data on joint pain and damage, quality of life (QOL), societal impacts, and costs of care were limited and inconsistent across the studies.

The review “revealed a lack of evidence” in adults with mild hemophilia A, Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues wrote in Haemophilia.

The researchers reviewed data from 10 studies conducted in Europe, 6 in North America, and 1 in Japan. Six studies were prospective cohort or registry studies, six were retrospective, and five studies were surveys or outcomes research.

The studies included 3,213 patients with mild hemophilia A aged 13 years or older. There were few details on treatment protocols, but patients received factor VIII concentrates, recombinant factor VIII, and desmopressin.

Most studies did not report mean ABRs. For the three that did, the mean ABRs were 0.44, 0.56, and 4.5. Six studies reported the percentage of patients with bleeding events, and those numbers ranged from 5.5% (1/18) to 90.7% (68/75).

Data on joint pain and damage were not standardized across studies, so the researchers were unable to draw any conclusions. One study showed no significant difference in Health Assessment Questionnaire pain score between patients with mild hemophilia A and control subjects. In another study, 5% of patients with mild hemophilia A reported having severe joint pain in the previous year, and 15% of patients reported moderate joint pain.

The researchers also found it difficult to draw conclusions about QOL. Three studies reported QOL data, and all used a different instrument.

In a study using the SF-36, general health and emotional role functioning were both significantly lower for patients with mild hemophilia A than for age-matched healthy control subjects (P less than .05). In a study using the SF-12, the physical component summary was significantly higher for patients with mild hemophilia A than for those with severe disease (P = .014).

In a study using the Haemo-QOL-A, there were no significant differences between patients with mild and severe hemophilia A. However, Dr. Peyvandi and colleagues noted that this study required long-term use of factor VIII concentrate, so the mild hemophilia A patients in this group were “probably not representative” of the overall mild hemophilia A population.

Societal impacts were difficult to assess because of a lack of standardization across studies. One study showed no significant difference in employment between patients with mild hemophilia A and healthy controls. In a U.S.-based study, patients with mild hemophilia A missed an average of 6.2 workdays per year, and 4.7 days were caused by their hemophilia. A study in Italy showed that patients with mild hemophilia A missed an average of 3.4 workdays per year.

Just two studies included data on health care costs for patients with mild hemophilia A. The mean cost of care was €793 per year in a study from Portugal published in 2015. In a U.S. study published in 1995, the annual cost of care was $22,182.

“Considering the limitations of the current body of evidence, higher-quality studies in this area are needed,” Dr. Peyvandi and colleagues wrote. “Such studies would report both bleeding and other clinical outcomes based on common definitions and for a representative population of mild [hemophilia A] adults. Areas for further research include more robust comparison to healthy controls or population norms, especially for QOL and other patient-reported outcomes.”

Seven of the eight researchers reported relationships, including employment, with BioMarin. Dr. Peyvandi reported relationships with Sanofi, Grifols, Novo Nordisk, Roche, Takeda, Sobi, Bioverativ, Spark Therapeutics, Sysmex, and CSL Behring.

[email protected]

SOURCE: Peyvandi F et al. Haemophilia. 2019 Jul 11. doi: 10.1111/hae.13777.

A literature review has failed to provide new insights regarding the burden of mild hemophilia A.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

In the 17 studies reviewed, mean annual bleeding rates (ABRs) were largely unreported. Data on joint pain and damage, quality of life (QOL), societal impacts, and costs of care were limited and inconsistent across the studies.

The review “revealed a lack of evidence” in adults with mild hemophilia A, Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues wrote in Haemophilia.

The researchers reviewed data from 10 studies conducted in Europe, 6 in North America, and 1 in Japan. Six studies were prospective cohort or registry studies, six were retrospective, and five studies were surveys or outcomes research.

The studies included 3,213 patients with mild hemophilia A aged 13 years or older. There were few details on treatment protocols, but patients received factor VIII concentrates, recombinant factor VIII, and desmopressin.

Most studies did not report mean ABRs. For the three that did, the mean ABRs were 0.44, 0.56, and 4.5. Six studies reported the percentage of patients with bleeding events, and those numbers ranged from 5.5% (1/18) to 90.7% (68/75).

Data on joint pain and damage were not standardized across studies, so the researchers were unable to draw any conclusions. One study showed no significant difference in Health Assessment Questionnaire pain score between patients with mild hemophilia A and control subjects. In another study, 5% of patients with mild hemophilia A reported having severe joint pain in the previous year, and 15% of patients reported moderate joint pain.

The researchers also found it difficult to draw conclusions about QOL. Three studies reported QOL data, and all used a different instrument.

In a study using the SF-36, general health and emotional role functioning were both significantly lower for patients with mild hemophilia A than for age-matched healthy control subjects (P less than .05). In a study using the SF-12, the physical component summary was significantly higher for patients with mild hemophilia A than for those with severe disease (P = .014).

In a study using the Haemo-QOL-A, there were no significant differences between patients with mild and severe hemophilia A. However, Dr. Peyvandi and colleagues noted that this study required long-term use of factor VIII concentrate, so the mild hemophilia A patients in this group were “probably not representative” of the overall mild hemophilia A population.

Societal impacts were difficult to assess because of a lack of standardization across studies. One study showed no significant difference in employment between patients with mild hemophilia A and healthy controls. In a U.S.-based study, patients with mild hemophilia A missed an average of 6.2 workdays per year, and 4.7 days were caused by their hemophilia. A study in Italy showed that patients with mild hemophilia A missed an average of 3.4 workdays per year.

Just two studies included data on health care costs for patients with mild hemophilia A. The mean cost of care was €793 per year in a study from Portugal published in 2015. In a U.S. study published in 1995, the annual cost of care was $22,182.

“Considering the limitations of the current body of evidence, higher-quality studies in this area are needed,” Dr. Peyvandi and colleagues wrote. “Such studies would report both bleeding and other clinical outcomes based on common definitions and for a representative population of mild [hemophilia A] adults. Areas for further research include more robust comparison to healthy controls or population norms, especially for QOL and other patient-reported outcomes.”

Seven of the eight researchers reported relationships, including employment, with BioMarin. Dr. Peyvandi reported relationships with Sanofi, Grifols, Novo Nordisk, Roche, Takeda, Sobi, Bioverativ, Spark Therapeutics, Sysmex, and CSL Behring.

[email protected]

SOURCE: Peyvandi F et al. Haemophilia. 2019 Jul 11. doi: 10.1111/hae.13777.

A literature review has failed to provide new insights regarding the burden of mild hemophilia A.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

In the 17 studies reviewed, mean annual bleeding rates (ABRs) were largely unreported. Data on joint pain and damage, quality of life (QOL), societal impacts, and costs of care were limited and inconsistent across the studies.

The review “revealed a lack of evidence” in adults with mild hemophilia A, Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues wrote in Haemophilia.

The researchers reviewed data from 10 studies conducted in Europe, 6 in North America, and 1 in Japan. Six studies were prospective cohort or registry studies, six were retrospective, and five studies were surveys or outcomes research.

The studies included 3,213 patients with mild hemophilia A aged 13 years or older. There were few details on treatment protocols, but patients received factor VIII concentrates, recombinant factor VIII, and desmopressin.

Most studies did not report mean ABRs. For the three that did, the mean ABRs were 0.44, 0.56, and 4.5. Six studies reported the percentage of patients with bleeding events, and those numbers ranged from 5.5% (1/18) to 90.7% (68/75).

Data on joint pain and damage were not standardized across studies, so the researchers were unable to draw any conclusions. One study showed no significant difference in Health Assessment Questionnaire pain score between patients with mild hemophilia A and control subjects. In another study, 5% of patients with mild hemophilia A reported having severe joint pain in the previous year, and 15% of patients reported moderate joint pain.

The researchers also found it difficult to draw conclusions about QOL. Three studies reported QOL data, and all used a different instrument.

In a study using the SF-36, general health and emotional role functioning were both significantly lower for patients with mild hemophilia A than for age-matched healthy control subjects (P less than .05). In a study using the SF-12, the physical component summary was significantly higher for patients with mild hemophilia A than for those with severe disease (P = .014).

In a study using the Haemo-QOL-A, there were no significant differences between patients with mild and severe hemophilia A. However, Dr. Peyvandi and colleagues noted that this study required long-term use of factor VIII concentrate, so the mild hemophilia A patients in this group were “probably not representative” of the overall mild hemophilia A population.

Societal impacts were difficult to assess because of a lack of standardization across studies. One study showed no significant difference in employment between patients with mild hemophilia A and healthy controls. In a U.S.-based study, patients with mild hemophilia A missed an average of 6.2 workdays per year, and 4.7 days were caused by their hemophilia. A study in Italy showed that patients with mild hemophilia A missed an average of 3.4 workdays per year.

Just two studies included data on health care costs for patients with mild hemophilia A. The mean cost of care was €793 per year in a study from Portugal published in 2015. In a U.S. study published in 1995, the annual cost of care was $22,182.

“Considering the limitations of the current body of evidence, higher-quality studies in this area are needed,” Dr. Peyvandi and colleagues wrote. “Such studies would report both bleeding and other clinical outcomes based on common definitions and for a representative population of mild [hemophilia A] adults. Areas for further research include more robust comparison to healthy controls or population norms, especially for QOL and other patient-reported outcomes.”

Seven of the eight researchers reported relationships, including employment, with BioMarin. Dr. Peyvandi reported relationships with Sanofi, Grifols, Novo Nordisk, Roche, Takeda, Sobi, Bioverativ, Spark Therapeutics, Sysmex, and CSL Behring.

[email protected]

SOURCE: Peyvandi F et al. Haemophilia. 2019 Jul 11. doi: 10.1111/hae.13777.

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.