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Reactions to reactions
When patients say they had “a reaction” to some treatment, they often don’t mean what we would call allergy or even intolerance. This doesn’t make their reluctance – or refusal – to consider what we suggest any less insistent.
I’ve lost track, for insistence, of the number of patients who called 2 days after I prescribed clindamycin lotion to complain that it “dried me out completely.”
When a customer in a cosmetic store or pharmacy returns a skin care cream because of that kind of “reaction,” the store takes it back, no questions asked. This is not just good business practice; in that context, both the customer and the salesperson use the word “reaction” the way laymen do, not the way doctors do.
If you doubt a reaction is real and say so, however gently, the response you may get is, “That may be true, Doctor, but my body is sensitive. I get strange reactions.”
Like most everyone else in practice, I use negotiating tactics, such as: “Stop the cream for 3 days, then try it again, but just in one spot in front of your left ear.”
Some patients agree to try this. Mostly, nothing happens, they resume the medication, and life goes on. For fearful people, we have to use something else. Sometimes patients and I run through a succession of options, each of which produces an inscrutable “reaction.”
As the years pass, I’ve gotten better at gauging the range of true reactions to medications. At the same time, the list of perplexing things patients complain about gets longer all the time. Lately, there’s been a run of them:
• The woman who used low-strength tretinoin cream all of twice and stopped 2 weeks ago who insisted that “my face is still all dried out.” I assured her that 2 days of tretinoin cannot damage the skin forever, but she remains unconvinced.
• The man who says that putting tretinoin on his face “made me dry out all over.”
• The mother who said her daughter stopped my steroid cream because “every time we used it, her tongue broke out in blisters.”
• The middle-aged woman who claimed, “I can’t take minocycline because it changed the color of my teeth and my eyes.”
• The young woman who puts clindamycin pads only on her right cheek, where she still has pimples, but not on the left, “because it makes the pimples go away on the cheek that has them, but on the other side it makes pimples come out.”
When I hear complaints like these, I just sigh and make a lateral move.
But sometimes I run out of lateral moves. The other month a woman told me that doxycycline made her “tired.” We tried minocycline, but that made her “irritable.” “My body is prone to strange reactions that no one else gets,” she explained. Then she asked for a third option.
“I honestly don’t know what to suggest,” I apologized. “Because your body reacts in ways that other people don’t, I can’t predict what some other treatment will do to you, even if it hasn’t done it to anyone else.”
She asked for her records, to get another opinion. I happily complied.
Speaking of weird “reactions,” there are of course the ones listed on e-scribing programs. Here are a couple:
• Hydrocortisone valerate has been associated with WARTS. (Capitalized)
• Hydrocortisone valerate has been associated with tinea cruris.
Make any sense to you? Me neither.
I end with a call I got the other day from a pharmacist. This concerned a patient for whom I had prescribed oral doxycycline and topical tretinoin. The message was, “Please call regarding drug interaction.”
When I got through, I politely asked the nature of this interaction. The pharmacist said she didn’t know exactly, but would look into it and fax me the details.
Half an hour later I got a sheet explaining the there is an increased risk of pseudotumor cerebri when patients take both oral tretinoin and oral tetracyclines.
That is correct: Not isotretinoin. Oral tretinoin. Used any oral tretinoin lately?
At any rate, the helpful pharmacist wrote at the bottom, “This interaction is flagged by several insurers for topical tretinoin too.”
Thank heavens for computer-generated warnings. Whatever would we do without them?
Besides, it’s nice to know that even after all these years, I can still react myself, with surprise.
Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].
When patients say they had “a reaction” to some treatment, they often don’t mean what we would call allergy or even intolerance. This doesn’t make their reluctance – or refusal – to consider what we suggest any less insistent.
I’ve lost track, for insistence, of the number of patients who called 2 days after I prescribed clindamycin lotion to complain that it “dried me out completely.”
When a customer in a cosmetic store or pharmacy returns a skin care cream because of that kind of “reaction,” the store takes it back, no questions asked. This is not just good business practice; in that context, both the customer and the salesperson use the word “reaction” the way laymen do, not the way doctors do.
If you doubt a reaction is real and say so, however gently, the response you may get is, “That may be true, Doctor, but my body is sensitive. I get strange reactions.”
Like most everyone else in practice, I use negotiating tactics, such as: “Stop the cream for 3 days, then try it again, but just in one spot in front of your left ear.”
Some patients agree to try this. Mostly, nothing happens, they resume the medication, and life goes on. For fearful people, we have to use something else. Sometimes patients and I run through a succession of options, each of which produces an inscrutable “reaction.”
As the years pass, I’ve gotten better at gauging the range of true reactions to medications. At the same time, the list of perplexing things patients complain about gets longer all the time. Lately, there’s been a run of them:
• The woman who used low-strength tretinoin cream all of twice and stopped 2 weeks ago who insisted that “my face is still all dried out.” I assured her that 2 days of tretinoin cannot damage the skin forever, but she remains unconvinced.
• The man who says that putting tretinoin on his face “made me dry out all over.”
• The mother who said her daughter stopped my steroid cream because “every time we used it, her tongue broke out in blisters.”
• The middle-aged woman who claimed, “I can’t take minocycline because it changed the color of my teeth and my eyes.”
• The young woman who puts clindamycin pads only on her right cheek, where she still has pimples, but not on the left, “because it makes the pimples go away on the cheek that has them, but on the other side it makes pimples come out.”
When I hear complaints like these, I just sigh and make a lateral move.
But sometimes I run out of lateral moves. The other month a woman told me that doxycycline made her “tired.” We tried minocycline, but that made her “irritable.” “My body is prone to strange reactions that no one else gets,” she explained. Then she asked for a third option.
“I honestly don’t know what to suggest,” I apologized. “Because your body reacts in ways that other people don’t, I can’t predict what some other treatment will do to you, even if it hasn’t done it to anyone else.”
She asked for her records, to get another opinion. I happily complied.
Speaking of weird “reactions,” there are of course the ones listed on e-scribing programs. Here are a couple:
• Hydrocortisone valerate has been associated with WARTS. (Capitalized)
• Hydrocortisone valerate has been associated with tinea cruris.
Make any sense to you? Me neither.
I end with a call I got the other day from a pharmacist. This concerned a patient for whom I had prescribed oral doxycycline and topical tretinoin. The message was, “Please call regarding drug interaction.”
When I got through, I politely asked the nature of this interaction. The pharmacist said she didn’t know exactly, but would look into it and fax me the details.
Half an hour later I got a sheet explaining the there is an increased risk of pseudotumor cerebri when patients take both oral tretinoin and oral tetracyclines.
That is correct: Not isotretinoin. Oral tretinoin. Used any oral tretinoin lately?
At any rate, the helpful pharmacist wrote at the bottom, “This interaction is flagged by several insurers for topical tretinoin too.”
Thank heavens for computer-generated warnings. Whatever would we do without them?
Besides, it’s nice to know that even after all these years, I can still react myself, with surprise.
Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].
When patients say they had “a reaction” to some treatment, they often don’t mean what we would call allergy or even intolerance. This doesn’t make their reluctance – or refusal – to consider what we suggest any less insistent.
I’ve lost track, for insistence, of the number of patients who called 2 days after I prescribed clindamycin lotion to complain that it “dried me out completely.”
When a customer in a cosmetic store or pharmacy returns a skin care cream because of that kind of “reaction,” the store takes it back, no questions asked. This is not just good business practice; in that context, both the customer and the salesperson use the word “reaction” the way laymen do, not the way doctors do.
If you doubt a reaction is real and say so, however gently, the response you may get is, “That may be true, Doctor, but my body is sensitive. I get strange reactions.”
Like most everyone else in practice, I use negotiating tactics, such as: “Stop the cream for 3 days, then try it again, but just in one spot in front of your left ear.”
Some patients agree to try this. Mostly, nothing happens, they resume the medication, and life goes on. For fearful people, we have to use something else. Sometimes patients and I run through a succession of options, each of which produces an inscrutable “reaction.”
As the years pass, I’ve gotten better at gauging the range of true reactions to medications. At the same time, the list of perplexing things patients complain about gets longer all the time. Lately, there’s been a run of them:
• The woman who used low-strength tretinoin cream all of twice and stopped 2 weeks ago who insisted that “my face is still all dried out.” I assured her that 2 days of tretinoin cannot damage the skin forever, but she remains unconvinced.
• The man who says that putting tretinoin on his face “made me dry out all over.”
• The mother who said her daughter stopped my steroid cream because “every time we used it, her tongue broke out in blisters.”
• The middle-aged woman who claimed, “I can’t take minocycline because it changed the color of my teeth and my eyes.”
• The young woman who puts clindamycin pads only on her right cheek, where she still has pimples, but not on the left, “because it makes the pimples go away on the cheek that has them, but on the other side it makes pimples come out.”
When I hear complaints like these, I just sigh and make a lateral move.
But sometimes I run out of lateral moves. The other month a woman told me that doxycycline made her “tired.” We tried minocycline, but that made her “irritable.” “My body is prone to strange reactions that no one else gets,” she explained. Then she asked for a third option.
“I honestly don’t know what to suggest,” I apologized. “Because your body reacts in ways that other people don’t, I can’t predict what some other treatment will do to you, even if it hasn’t done it to anyone else.”
She asked for her records, to get another opinion. I happily complied.
Speaking of weird “reactions,” there are of course the ones listed on e-scribing programs. Here are a couple:
• Hydrocortisone valerate has been associated with WARTS. (Capitalized)
• Hydrocortisone valerate has been associated with tinea cruris.
Make any sense to you? Me neither.
I end with a call I got the other day from a pharmacist. This concerned a patient for whom I had prescribed oral doxycycline and topical tretinoin. The message was, “Please call regarding drug interaction.”
When I got through, I politely asked the nature of this interaction. The pharmacist said she didn’t know exactly, but would look into it and fax me the details.
Half an hour later I got a sheet explaining the there is an increased risk of pseudotumor cerebri when patients take both oral tretinoin and oral tetracyclines.
That is correct: Not isotretinoin. Oral tretinoin. Used any oral tretinoin lately?
At any rate, the helpful pharmacist wrote at the bottom, “This interaction is flagged by several insurers for topical tretinoin too.”
Thank heavens for computer-generated warnings. Whatever would we do without them?
Besides, it’s nice to know that even after all these years, I can still react myself, with surprise.
Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].
Accident or incident?
In May 2016, a 4-year-old managed to get into the gorilla enclosure at the Cincinnati Zoo. In a successful attempt to remove the child before he could be seriously injured, the zoo officials shot and killed the gorilla. While there has been some debate as to whether the situation warranted the use of deadly force, there is general agreement that we should value a human life over that of an animal.
However, the debate that continues to simmer focuses on whether the child’s parents share in any culpability for the event. I suspect we will never know enough of the details to make a judgment on this question. And faced with that uncertainty, what I am going to say in the next few paragraphs does not apply to the situation at the Cincinnati Zoo. I am using that event only as a place to start a discussion.
You and I have seen scores of children who, because of their immaturity and to a larger extent to their temperament, are adventuresome and resistant to attempts by those who would like to keep them safe. You could label them as risk takers, but I don’t think those children are perceptive enough to understand that what they are doing is risky.
You could call them accident prone, but this raises the question of how many events that end in injury or death are really accidental. Almost all of those tragedies aren’t intentional. But how many were preventable? Of course, that depends on how broadly you define preventable. How far back in the chain of events that preceded an incident are you willing to realistically assign causality or culpability?
For example, a mother is standing on the sidewalk of busy intersection with a traffic light, holding her 3-year-old’s hand. Her cell phone alerts her of a text, she drops his hand to check it, and in an instant he darts out into the travel lane to grab what turns out to be an empty candy wrapper and is struck by a car. Was this an accident?
I suspect that if we interviewed family friends, neighbors, and maybe even the child’s pediatrician, we would learn of several dozen examples of the child’s unusually impulsive behavior. We also might learn that he had been resistant to his mother’s attempts to set limits and modify his behavior. In other words, his past history suggests that he was an “accident” waiting to happen.
Who is culpable here? Should the driver have been more aware of the pedestrians who were waiting to cross and, seeing that one was a young child, realized that some little children are more impulsive than others and driven more prudently? Should the child’s mother have accepted the fact that while some 3-year-olds can be under “voice control,” her son was certainly not one of those and ignored her phone?
Should the child’s pediatrician, who was aware of his temperament and impulsivity, have spent more time with the family on how to manage his behavior? Dr. William J. Turtle published a book in the 1970s titled, “Dr. Turtle’s Babies,” in which among other sage advice, he suggests most if not all toddlers should be fitted with a harness until they can be trusted. While you and I may have trouble selling this concept to parents – particularly parents of post toddlers – a harness or wrist-restraining tether might have saved this 3-year-old’s life. Whether a child’s impulsivity is age appropriate or pathologic, we must include advice on its management in our anticipatory guidance. There are very few true accidents, many are incidents that were predictable – and to some extent – preventable.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
In May 2016, a 4-year-old managed to get into the gorilla enclosure at the Cincinnati Zoo. In a successful attempt to remove the child before he could be seriously injured, the zoo officials shot and killed the gorilla. While there has been some debate as to whether the situation warranted the use of deadly force, there is general agreement that we should value a human life over that of an animal.
However, the debate that continues to simmer focuses on whether the child’s parents share in any culpability for the event. I suspect we will never know enough of the details to make a judgment on this question. And faced with that uncertainty, what I am going to say in the next few paragraphs does not apply to the situation at the Cincinnati Zoo. I am using that event only as a place to start a discussion.
You and I have seen scores of children who, because of their immaturity and to a larger extent to their temperament, are adventuresome and resistant to attempts by those who would like to keep them safe. You could label them as risk takers, but I don’t think those children are perceptive enough to understand that what they are doing is risky.
You could call them accident prone, but this raises the question of how many events that end in injury or death are really accidental. Almost all of those tragedies aren’t intentional. But how many were preventable? Of course, that depends on how broadly you define preventable. How far back in the chain of events that preceded an incident are you willing to realistically assign causality or culpability?
For example, a mother is standing on the sidewalk of busy intersection with a traffic light, holding her 3-year-old’s hand. Her cell phone alerts her of a text, she drops his hand to check it, and in an instant he darts out into the travel lane to grab what turns out to be an empty candy wrapper and is struck by a car. Was this an accident?
I suspect that if we interviewed family friends, neighbors, and maybe even the child’s pediatrician, we would learn of several dozen examples of the child’s unusually impulsive behavior. We also might learn that he had been resistant to his mother’s attempts to set limits and modify his behavior. In other words, his past history suggests that he was an “accident” waiting to happen.
Who is culpable here? Should the driver have been more aware of the pedestrians who were waiting to cross and, seeing that one was a young child, realized that some little children are more impulsive than others and driven more prudently? Should the child’s mother have accepted the fact that while some 3-year-olds can be under “voice control,” her son was certainly not one of those and ignored her phone?
Should the child’s pediatrician, who was aware of his temperament and impulsivity, have spent more time with the family on how to manage his behavior? Dr. William J. Turtle published a book in the 1970s titled, “Dr. Turtle’s Babies,” in which among other sage advice, he suggests most if not all toddlers should be fitted with a harness until they can be trusted. While you and I may have trouble selling this concept to parents – particularly parents of post toddlers – a harness or wrist-restraining tether might have saved this 3-year-old’s life. Whether a child’s impulsivity is age appropriate or pathologic, we must include advice on its management in our anticipatory guidance. There are very few true accidents, many are incidents that were predictable – and to some extent – preventable.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
In May 2016, a 4-year-old managed to get into the gorilla enclosure at the Cincinnati Zoo. In a successful attempt to remove the child before he could be seriously injured, the zoo officials shot and killed the gorilla. While there has been some debate as to whether the situation warranted the use of deadly force, there is general agreement that we should value a human life over that of an animal.
However, the debate that continues to simmer focuses on whether the child’s parents share in any culpability for the event. I suspect we will never know enough of the details to make a judgment on this question. And faced with that uncertainty, what I am going to say in the next few paragraphs does not apply to the situation at the Cincinnati Zoo. I am using that event only as a place to start a discussion.
You and I have seen scores of children who, because of their immaturity and to a larger extent to their temperament, are adventuresome and resistant to attempts by those who would like to keep them safe. You could label them as risk takers, but I don’t think those children are perceptive enough to understand that what they are doing is risky.
You could call them accident prone, but this raises the question of how many events that end in injury or death are really accidental. Almost all of those tragedies aren’t intentional. But how many were preventable? Of course, that depends on how broadly you define preventable. How far back in the chain of events that preceded an incident are you willing to realistically assign causality or culpability?
For example, a mother is standing on the sidewalk of busy intersection with a traffic light, holding her 3-year-old’s hand. Her cell phone alerts her of a text, she drops his hand to check it, and in an instant he darts out into the travel lane to grab what turns out to be an empty candy wrapper and is struck by a car. Was this an accident?
I suspect that if we interviewed family friends, neighbors, and maybe even the child’s pediatrician, we would learn of several dozen examples of the child’s unusually impulsive behavior. We also might learn that he had been resistant to his mother’s attempts to set limits and modify his behavior. In other words, his past history suggests that he was an “accident” waiting to happen.
Who is culpable here? Should the driver have been more aware of the pedestrians who were waiting to cross and, seeing that one was a young child, realized that some little children are more impulsive than others and driven more prudently? Should the child’s mother have accepted the fact that while some 3-year-olds can be under “voice control,” her son was certainly not one of those and ignored her phone?
Should the child’s pediatrician, who was aware of his temperament and impulsivity, have spent more time with the family on how to manage his behavior? Dr. William J. Turtle published a book in the 1970s titled, “Dr. Turtle’s Babies,” in which among other sage advice, he suggests most if not all toddlers should be fitted with a harness until they can be trusted. While you and I may have trouble selling this concept to parents – particularly parents of post toddlers – a harness or wrist-restraining tether might have saved this 3-year-old’s life. Whether a child’s impulsivity is age appropriate or pathologic, we must include advice on its management in our anticipatory guidance. There are very few true accidents, many are incidents that were predictable – and to some extent – preventable.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
Novel anticoagulants linked to lower intracranial hemorrhages, higher GI bleeds
Copenhagen – A real-life comparison of major bleeding risk with anticoagulants showed that in-hospital mortality was lower with novel oral agents than with vitamin K antagonists, but the risk varied by bleeding site.
Novel oral anticoagulants (NOACs) such as dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) were associated in randomized phase III clinical trials with lower incidences of major bleeding than vitamin K antagonists (VKA) such as warfarin, and the newer, heavily advertised agents are widely used in clinical practice, noted Dr. Laura Franco of the Stroke Unit at the University of Perugia, Italy.
“But there is [little] information about the management and outcomes of major bleeding with NOACs in real life,” she said at a briefing at the annual congress of the European Hematology Association.
To rectify this situation, Dr. Franco and her colleagues at nine Italian hospitals and the NOAC registry based in Dresden, Germany, looked at 30-day mortality and other outcomes among 874 consecutive patients admitted for a major bleeding episode from September 2013 through May 2016. In all, 220 of the patients were on NOACs, and 654 were on VKAs.
Intracranial bleeds occurred in 44% of all patients, but were significantly less common among patients on NOACs than on VKAs (22% vs, 52%, respectively, odds ratio 0.26, P less than .001), whereas gastrointestinal bleeds, which occurred in 30% of all patients, were more frequent with the newer oral agents than with the older VKAs (46% vs. 30%, OR 2.69, P less than .001).
Deaths within 30 days of emergency department admission were less frequent with NOACs (10% vs. 17%, hazard ratio 0.56, P = .012).
“But when we analyzed the subpopulation of patients with different sites of bleeding, we saw that among intracranial hemorrhage, the rate was equal among NOAC and VKAs patients, 25% in both groups,” Dr. Franco said.
Deaths from gastrointestinal bleeding were numerically lower among patients on NOACs (7% vs. 10%), but this difference was not statistically significant.
“The great advantages of the new oral anticoagulants are the reduced risk in intracranial hemorrhage, so we showed that the lower mortality is not due to an intrinsic capacity to reduce deaths by NOACs as compared to VKAs, but to a different pattern of bleeding sites,” Dr. Franco said.
The study funding source was not disclosed. Dr. Franco did not report relevant disclosures.
Copenhagen – A real-life comparison of major bleeding risk with anticoagulants showed that in-hospital mortality was lower with novel oral agents than with vitamin K antagonists, but the risk varied by bleeding site.
Novel oral anticoagulants (NOACs) such as dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) were associated in randomized phase III clinical trials with lower incidences of major bleeding than vitamin K antagonists (VKA) such as warfarin, and the newer, heavily advertised agents are widely used in clinical practice, noted Dr. Laura Franco of the Stroke Unit at the University of Perugia, Italy.
“But there is [little] information about the management and outcomes of major bleeding with NOACs in real life,” she said at a briefing at the annual congress of the European Hematology Association.
To rectify this situation, Dr. Franco and her colleagues at nine Italian hospitals and the NOAC registry based in Dresden, Germany, looked at 30-day mortality and other outcomes among 874 consecutive patients admitted for a major bleeding episode from September 2013 through May 2016. In all, 220 of the patients were on NOACs, and 654 were on VKAs.
Intracranial bleeds occurred in 44% of all patients, but were significantly less common among patients on NOACs than on VKAs (22% vs, 52%, respectively, odds ratio 0.26, P less than .001), whereas gastrointestinal bleeds, which occurred in 30% of all patients, were more frequent with the newer oral agents than with the older VKAs (46% vs. 30%, OR 2.69, P less than .001).
Deaths within 30 days of emergency department admission were less frequent with NOACs (10% vs. 17%, hazard ratio 0.56, P = .012).
“But when we analyzed the subpopulation of patients with different sites of bleeding, we saw that among intracranial hemorrhage, the rate was equal among NOAC and VKAs patients, 25% in both groups,” Dr. Franco said.
Deaths from gastrointestinal bleeding were numerically lower among patients on NOACs (7% vs. 10%), but this difference was not statistically significant.
“The great advantages of the new oral anticoagulants are the reduced risk in intracranial hemorrhage, so we showed that the lower mortality is not due to an intrinsic capacity to reduce deaths by NOACs as compared to VKAs, but to a different pattern of bleeding sites,” Dr. Franco said.
The study funding source was not disclosed. Dr. Franco did not report relevant disclosures.
Copenhagen – A real-life comparison of major bleeding risk with anticoagulants showed that in-hospital mortality was lower with novel oral agents than with vitamin K antagonists, but the risk varied by bleeding site.
Novel oral anticoagulants (NOACs) such as dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) were associated in randomized phase III clinical trials with lower incidences of major bleeding than vitamin K antagonists (VKA) such as warfarin, and the newer, heavily advertised agents are widely used in clinical practice, noted Dr. Laura Franco of the Stroke Unit at the University of Perugia, Italy.
“But there is [little] information about the management and outcomes of major bleeding with NOACs in real life,” she said at a briefing at the annual congress of the European Hematology Association.
To rectify this situation, Dr. Franco and her colleagues at nine Italian hospitals and the NOAC registry based in Dresden, Germany, looked at 30-day mortality and other outcomes among 874 consecutive patients admitted for a major bleeding episode from September 2013 through May 2016. In all, 220 of the patients were on NOACs, and 654 were on VKAs.
Intracranial bleeds occurred in 44% of all patients, but were significantly less common among patients on NOACs than on VKAs (22% vs, 52%, respectively, odds ratio 0.26, P less than .001), whereas gastrointestinal bleeds, which occurred in 30% of all patients, were more frequent with the newer oral agents than with the older VKAs (46% vs. 30%, OR 2.69, P less than .001).
Deaths within 30 days of emergency department admission were less frequent with NOACs (10% vs. 17%, hazard ratio 0.56, P = .012).
“But when we analyzed the subpopulation of patients with different sites of bleeding, we saw that among intracranial hemorrhage, the rate was equal among NOAC and VKAs patients, 25% in both groups,” Dr. Franco said.
Deaths from gastrointestinal bleeding were numerically lower among patients on NOACs (7% vs. 10%), but this difference was not statistically significant.
“The great advantages of the new oral anticoagulants are the reduced risk in intracranial hemorrhage, so we showed that the lower mortality is not due to an intrinsic capacity to reduce deaths by NOACs as compared to VKAs, but to a different pattern of bleeding sites,” Dr. Franco said.
The study funding source was not disclosed. Dr. Franco did not report relevant disclosures.
At THE EHA CONGRESS
Key clinical point:. Lower rates of 30-day mortality from major bleeding with novel oral anticoagulants (NOACs) may be due to different patterns of bleeding sites.
Major finding: 30-day mortality rates were 10% with NOACs vs. 17% with vitamin K antagonists (hazard ratio 0.56, P = .012)
Data source: Study of 874 consecutive patients admitted to hospitals in Italy and Germany for major bleeding episodes.Disclosures: The study funding source was not disclosed. Dr. Franco did not report relevant disclosures.
Like tobacco, recent marijuana use decreases exhaled nitric oxide
Recent marijuana use may have an effect similar to recent tobacco use with regard to decreased production of exhaled nitric oxide (eNO), but a very different effect on forced vital capacity (FVC), according to the results of a study published in Chest.
Dr. Stefania I. Papatheodorou from the Cyprus International Institute for Environmental and Public Health, Limassol, Cyprus, in association with the Harvard T. H. Chan School of Public Health, and her colleagues conducted a retrospective analysis of National Health and Nutrition Examination Survey (NHANES) data collected from 10,327 people aged 18-59 years between 2007 to 2012. Respondents completed a questionnaire on illicit drug use and were given a physical examination. Outcomes of interest for this study were eNO levels and pulmonary function measurements including the forced expiratory volume in 1 second (FEV1), FVC, the FEV1/FVC ratio, and the average forced expiratory flow during the mid (25%-75%) portion of the FVC (FEF25%-75%) (Chest. 2016 Jan 16. doi: 10.1016/j.chest.2015.12.033).
The population available for analysis included 4,797 people who reported never having used marijuana, and 4,084 who reported past use. The recent users were divided into two groups; 555 and 891 respondents who reported using marijuana 5-30 days and 0-4 days before their examinations, respectively. The study results from age-adjusted analyses standardized to the 2000 U.S. Census population indicated that both past and current users had significantly lower eNO levels (in parts per billion) than those that had never used (all P less than .001). The same analysis demonstrated that FEV1, FVC, and FEV1/FVC ratios were all higher in current and past users than in never users (all P less than .001).
Using a multivariable model adjusted for age, sex, race/ethnicity, height, education level, income, marital status, asthma, tobacco use in pack-years, smoking category, and body mass index, both the 0-4 day users and the 5-30 day users showed significantly decreased eNO levels, compared with never users (-7%, 95% confidence interval -12% to -2%, P = .03; -13%, CI -18% to -8%, P less than .001, respectively). Additionally, recent users in the 0-4 day group had significantly higher FEV1 measures than never users (89 mL, CI 29-150, P = 0.005), as well as lower FEV1/FVC ratios (-.02, CI –.03 to –.01, P = .003).
Regarding the broader implications of their study findings, Dr. Papatheodorou and colleagues stated, “Given that nitric oxide plays a role in inflammatory and immune defense pathways in the respiratory system and is a mediator of vasodilation in the pulmonary and systemic vasculature, it would be useful to further explore the associations between marijuana use and vascular and pulmonary function in randomized trials.”
Dr. Mary B. Rice received funding from the Institute for Environmental Sciences. The other authors reported no conflicts of interest.
Recent marijuana use may have an effect similar to recent tobacco use with regard to decreased production of exhaled nitric oxide (eNO), but a very different effect on forced vital capacity (FVC), according to the results of a study published in Chest.
Dr. Stefania I. Papatheodorou from the Cyprus International Institute for Environmental and Public Health, Limassol, Cyprus, in association with the Harvard T. H. Chan School of Public Health, and her colleagues conducted a retrospective analysis of National Health and Nutrition Examination Survey (NHANES) data collected from 10,327 people aged 18-59 years between 2007 to 2012. Respondents completed a questionnaire on illicit drug use and were given a physical examination. Outcomes of interest for this study were eNO levels and pulmonary function measurements including the forced expiratory volume in 1 second (FEV1), FVC, the FEV1/FVC ratio, and the average forced expiratory flow during the mid (25%-75%) portion of the FVC (FEF25%-75%) (Chest. 2016 Jan 16. doi: 10.1016/j.chest.2015.12.033).
The population available for analysis included 4,797 people who reported never having used marijuana, and 4,084 who reported past use. The recent users were divided into two groups; 555 and 891 respondents who reported using marijuana 5-30 days and 0-4 days before their examinations, respectively. The study results from age-adjusted analyses standardized to the 2000 U.S. Census population indicated that both past and current users had significantly lower eNO levels (in parts per billion) than those that had never used (all P less than .001). The same analysis demonstrated that FEV1, FVC, and FEV1/FVC ratios were all higher in current and past users than in never users (all P less than .001).
Using a multivariable model adjusted for age, sex, race/ethnicity, height, education level, income, marital status, asthma, tobacco use in pack-years, smoking category, and body mass index, both the 0-4 day users and the 5-30 day users showed significantly decreased eNO levels, compared with never users (-7%, 95% confidence interval -12% to -2%, P = .03; -13%, CI -18% to -8%, P less than .001, respectively). Additionally, recent users in the 0-4 day group had significantly higher FEV1 measures than never users (89 mL, CI 29-150, P = 0.005), as well as lower FEV1/FVC ratios (-.02, CI –.03 to –.01, P = .003).
Regarding the broader implications of their study findings, Dr. Papatheodorou and colleagues stated, “Given that nitric oxide plays a role in inflammatory and immune defense pathways in the respiratory system and is a mediator of vasodilation in the pulmonary and systemic vasculature, it would be useful to further explore the associations between marijuana use and vascular and pulmonary function in randomized trials.”
Dr. Mary B. Rice received funding from the Institute for Environmental Sciences. The other authors reported no conflicts of interest.
Recent marijuana use may have an effect similar to recent tobacco use with regard to decreased production of exhaled nitric oxide (eNO), but a very different effect on forced vital capacity (FVC), according to the results of a study published in Chest.
Dr. Stefania I. Papatheodorou from the Cyprus International Institute for Environmental and Public Health, Limassol, Cyprus, in association with the Harvard T. H. Chan School of Public Health, and her colleagues conducted a retrospective analysis of National Health and Nutrition Examination Survey (NHANES) data collected from 10,327 people aged 18-59 years between 2007 to 2012. Respondents completed a questionnaire on illicit drug use and were given a physical examination. Outcomes of interest for this study were eNO levels and pulmonary function measurements including the forced expiratory volume in 1 second (FEV1), FVC, the FEV1/FVC ratio, and the average forced expiratory flow during the mid (25%-75%) portion of the FVC (FEF25%-75%) (Chest. 2016 Jan 16. doi: 10.1016/j.chest.2015.12.033).
The population available for analysis included 4,797 people who reported never having used marijuana, and 4,084 who reported past use. The recent users were divided into two groups; 555 and 891 respondents who reported using marijuana 5-30 days and 0-4 days before their examinations, respectively. The study results from age-adjusted analyses standardized to the 2000 U.S. Census population indicated that both past and current users had significantly lower eNO levels (in parts per billion) than those that had never used (all P less than .001). The same analysis demonstrated that FEV1, FVC, and FEV1/FVC ratios were all higher in current and past users than in never users (all P less than .001).
Using a multivariable model adjusted for age, sex, race/ethnicity, height, education level, income, marital status, asthma, tobacco use in pack-years, smoking category, and body mass index, both the 0-4 day users and the 5-30 day users showed significantly decreased eNO levels, compared with never users (-7%, 95% confidence interval -12% to -2%, P = .03; -13%, CI -18% to -8%, P less than .001, respectively). Additionally, recent users in the 0-4 day group had significantly higher FEV1 measures than never users (89 mL, CI 29-150, P = 0.005), as well as lower FEV1/FVC ratios (-.02, CI –.03 to –.01, P = .003).
Regarding the broader implications of their study findings, Dr. Papatheodorou and colleagues stated, “Given that nitric oxide plays a role in inflammatory and immune defense pathways in the respiratory system and is a mediator of vasodilation in the pulmonary and systemic vasculature, it would be useful to further explore the associations between marijuana use and vascular and pulmonary function in randomized trials.”
Dr. Mary B. Rice received funding from the Institute for Environmental Sciences. The other authors reported no conflicts of interest.
FROM CHEST
Key clinical point: Recent marijuana use can have acute negative effects on exhaled nitric oxide levels and aspects of pulmonary functioning.
Major finding: Current marijuana users showed significantly decreased eNO levels, compared with never users (-7% and -13% for those using within 0-4 days and within 5 to 30 days of examination, respectively).
Data sources: National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012
Disclosures: Dr. Mary B. Rice received funding from the Institute for Environmental Sciences. The other authors reported no conflicts of interest.
2015-2016 flu season slower and milder than past 3 years
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
FROM THE MMWR
2015-2016 flu season slower and milder than past 3 years
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.
Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)
“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.
“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.
The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.
Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.
The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.
Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).
CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.
Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.
Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.
Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).
“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”
As a CDC employee, Dr. Davlin had no financial disclosures.
On Twitter @Alz_Gal
FROM THE MMWR
Key clinical point: The last flu season peaked later, and killed fewer people than the last three seasons.
Major finding: The overall death rate was 31/100,000, with a peak of 8% occurring in March.
Data source: Numbers were drawn from CDC databases and other national influenza surveillance programs.
Disclosures: As a CDC employee, Dr. Davlin had no financial disclosures.
Inherited thrombocytopenia type is a risk factor for hematologic cancers
Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).
“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.
At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.
They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.
The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.
The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.
The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.
This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.
The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”
Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.
Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.
Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.
Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.
The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.
Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).
“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.
At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.
They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.
The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.
The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.
The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.
This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.
The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”
Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.
Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.
Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.
Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.
The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.
Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).
“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.
At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.
They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.
The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.
The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.
The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.
This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.
The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”
Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.
Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.
Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.
Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.
The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.
At THE EHA CONGRESS
Key clinical point: ETV6-related thrombocytopenia (EV6-RT) appears to predispose carriers to acute lymphoblastic leukemia and other hematologic cancers.
Major finding: Four of 20 patients with ETV6-RT had childhood ALL, and one developed JAK2-positive polycythemia vera at age 37.
Data source: Study of clinical and laboratory findings in 20 patients with EV6-RT.
Disclosures: The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.
Persistent post-therapy mutations may spark AML relapse
Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.
Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.
“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.
The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.
AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.
To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.
The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.
A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.
“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.
Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.
As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).
In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008).
“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.
Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.
“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.
“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.
The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.
Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.
Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.
“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.
The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.
AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.
To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.
The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.
A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.
“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.
Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.
As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).
In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008).
“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.
Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.
“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.
“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.
The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.
Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.
Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.
“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.
The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.
AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.
To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.
The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.
A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.
“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.
Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.
As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).
In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008).
“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.
Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.
“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.
“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.
The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.
At THE EHA CONGRESS
Key clinical point:. The higher risk of acute myeloid leukemia relapse among older patients may be due to persistent pre-leukemic mutations.
Major finding: Mutations persistent after chemotherapy were significantly more common among older patients, and were associated with worse outcomes.
Data source: Analysis of pre- and post-treatment bone marrow and blood samples from 107 adults with AML,
Disclosures: The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.
Team discovers 2 new subtypes of pediatric BCP ALL
Image courtesy Spencer Phillips
Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).
The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.
Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.
The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.
They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.
The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.
The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.
The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.
The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."
The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.
According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.
“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”
The investigators published their work in Nature Communications.
The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne. 
Image courtesy Spencer Phillips
Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).
The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.
Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.
The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.
They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.
The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.
The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.
The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.
The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."
The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.
According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.
“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”
The investigators published their work in Nature Communications.
The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne.
Image courtesy Spencer Phillips
Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).
The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.
Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.
The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.
They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.
The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.
The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.
The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.
The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."
The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.
According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.
“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”
The investigators published their work in Nature Communications.
The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne.
Potential new ways to supply islet cells to diabetes patients
NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.
Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.
At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.
“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.
The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.
The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.
At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.
However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.
“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”
The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.
The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.
This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.
Dr. Cowan and Dr. Cooper reported having no financial disclosures.
NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.
Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.
At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.
“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.
The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.
The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.
At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.
However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.
“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”
The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.
The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.
This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.
Dr. Cowan and Dr. Cooper reported having no financial disclosures.
NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.
Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.
At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.
“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.
The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.
The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.
At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.
However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.
“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”
The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.
The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.
This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.
Dr. Cowan and Dr. Cooper reported having no financial disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: Islet cells from pigs and “universal donor” cells offer potential to control blood-glucose in humans.
Major finding: Transplanted pig islet cells achieved blood glucose control in recipient monkeys for up to 2 years, and gene editing may enable researchers to create stem cells that may avoid the body’s natural immune response.
Data source: Animal studies of pig islet cell transplants and concept studies of universal donor stem cells.
Disclosures: Dr. Cowan and Dr. Cooper reported having no financial disclosures.
