LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

[email protected]

On Twitter @mitchelzoler

LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

[email protected]

On Twitter @mitchelzoler

LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

[email protected]

On Twitter @mitchelzoler

Colorectal cancers are among the most common cancers worldwide, and there is a high mortality rate for advanced-stage disease. Approximately 132,000 new cases of colorectal cancer will be diagnosed in the United States in 2015, and approximately 40,000 of these cases will be primary rectal cancers. The incidence and mortality rates have been steadily declining over the past two decades, largely through advances in screening and improvements in treatment. However, rectal cancer remains a significant cause of morbidity and mortality in the United States and worldwide.

To read the full article in PDF:

Click here

Colorectal cancers are among the most common cancers worldwide, and there is a high mortality rate for advanced-stage disease. Approximately 132,000 new cases of colorectal cancer will be diagnosed in the United States in 2015, and approximately 40,000 of these cases will be primary rectal cancers. The incidence and mortality rates have been steadily declining over the past two decades, largely through advances in screening and improvements in treatment. However, rectal cancer remains a significant cause of morbidity and mortality in the United States and worldwide.

To read the full article in PDF:

Click here

Colorectal cancers are among the most common cancers worldwide, and there is a high mortality rate for advanced-stage disease. Approximately 132,000 new cases of colorectal cancer will be diagnosed in the United States in 2015, and approximately 40,000 of these cases will be primary rectal cancers. The incidence and mortality rates have been steadily declining over the past two decades, largely through advances in screening and improvements in treatment. However, rectal cancer remains a significant cause of morbidity and mortality in the United States and worldwide.

To read the full article in PDF:

Click here

Okay, I admit that from time to time I have embellished the anecdotes that I include in these letters. Sometimes, I feel I need to make sure that you are paying attention. But this time, I am relating this story in its true, unvarnished state.

Two mature women with whom I am acquainted (No, one was not my wife!) had just finished their habitual Saturday morning walk through a wooded upper middle class neighborhood here in town. It was nine o’clock in the morning and the sun was shining. Suddenly, a mangy-looking fox trotted out of the woods and down the road toward them. Aware that from time to time local raccoons, skunks, and foxes have tested positive for rabies, these women began to run and flagged down the first car they saw, and without a word hopped in the back seat.

The surprised occupants of the vehicle were two mature men. You might call them strangers, but here in Maine, we don’t have any strangers. We have tourists. If a fellow Mainer doesn’t know you, he probably knows two people with whom you are acquainted.

As the women began to breathlessly explain their actions, one of the women felt a searing pain in her right thigh and assumed she had torn a muscle as she sprinted away from the fox. Within a few hundred yards, the car began to fill with smoke. Believing that the vehicle was on fire, all four occupants tumbled out into the street like four carnival clowns.

It quickly became clear that the cause of the smoke and the searing pain was that the woman’s pants were on fire. Throwing all caution and modesty to the wind, she quickly shed her pants in the middle of the road and in full view of these men, with whom it turns out she does share several acquaintances.

The source of the fire was the woman’s cell phone. The resulting injury was a palm-size, painful, deep, second-degree burn of her anterior thigh. In a quick Internet search, you will discover several very similar stories – minus the fox and the strangers. Some of the victims were children.

It turns out some cell phones have a tendency to spontaneously explode and/or catch fire. There seems to be no common factor in the events, although some of the ultrathin and flexible cell phones may be more prone to conflagration. However, the victim in our scenario has a storied past with cell phones. She has dropped them in the toilet at least once (history is a little unclear here on the exact number). On another occasion, she placed one in the sink of a public restroom, we can assume to prevent a second or third toilet submersion. As she approached the sink to retrieve it, the clever water-saving faucet – sensing her presence – turned itself on. But in the fox and fire incident, she denies any previous submersions or unusual events with this particular phone. A lawyer is now involved.

So while you and I as pediatricians may be concerned about the relationship between cell phones and health of our patients primarily because cell phones can be a dangerous distraction for young drivers, cyclists, and pedestrians, I share this anecdote to make you aware of another of their health hazards. You also may want to reconsider where you carry your cell phone.

I am not worried myself. I have a little flip phone for which I pay $100 for 500 minutes of usage a year, way more than I need or use. It couldn’t be considered a smartphone as its only noteworthy skill is taking pictures of the inside of my pants pocket. I suspect that its battery must be so small and impotent that even if it decides to self-immolate, I doubt I will notice. However, I do worry about scraggly-looking foxes meandering through my neighborhood.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

Okay, I admit that from time to time I have embellished the anecdotes that I include in these letters. Sometimes, I feel I need to make sure that you are paying attention. But this time, I am relating this story in its true, unvarnished state.

Two mature women with whom I am acquainted (No, one was not my wife!) had just finished their habitual Saturday morning walk through a wooded upper middle class neighborhood here in town. It was nine o’clock in the morning and the sun was shining. Suddenly, a mangy-looking fox trotted out of the woods and down the road toward them. Aware that from time to time local raccoons, skunks, and foxes have tested positive for rabies, these women began to run and flagged down the first car they saw, and without a word hopped in the back seat.

The surprised occupants of the vehicle were two mature men. You might call them strangers, but here in Maine, we don’t have any strangers. We have tourists. If a fellow Mainer doesn’t know you, he probably knows two people with whom you are acquainted.

As the women began to breathlessly explain their actions, one of the women felt a searing pain in her right thigh and assumed she had torn a muscle as she sprinted away from the fox. Within a few hundred yards, the car began to fill with smoke. Believing that the vehicle was on fire, all four occupants tumbled out into the street like four carnival clowns.

It quickly became clear that the cause of the smoke and the searing pain was that the woman’s pants were on fire. Throwing all caution and modesty to the wind, she quickly shed her pants in the middle of the road and in full view of these men, with whom it turns out she does share several acquaintances.

The source of the fire was the woman’s cell phone. The resulting injury was a palm-size, painful, deep, second-degree burn of her anterior thigh. In a quick Internet search, you will discover several very similar stories – minus the fox and the strangers. Some of the victims were children.

It turns out some cell phones have a tendency to spontaneously explode and/or catch fire. There seems to be no common factor in the events, although some of the ultrathin and flexible cell phones may be more prone to conflagration. However, the victim in our scenario has a storied past with cell phones. She has dropped them in the toilet at least once (history is a little unclear here on the exact number). On another occasion, she placed one in the sink of a public restroom, we can assume to prevent a second or third toilet submersion. As she approached the sink to retrieve it, the clever water-saving faucet – sensing her presence – turned itself on. But in the fox and fire incident, she denies any previous submersions or unusual events with this particular phone. A lawyer is now involved.

So while you and I as pediatricians may be concerned about the relationship between cell phones and health of our patients primarily because cell phones can be a dangerous distraction for young drivers, cyclists, and pedestrians, I share this anecdote to make you aware of another of their health hazards. You also may want to reconsider where you carry your cell phone.

I am not worried myself. I have a little flip phone for which I pay $100 for 500 minutes of usage a year, way more than I need or use. It couldn’t be considered a smartphone as its only noteworthy skill is taking pictures of the inside of my pants pocket. I suspect that its battery must be so small and impotent that even if it decides to self-immolate, I doubt I will notice. However, I do worry about scraggly-looking foxes meandering through my neighborhood.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

Okay, I admit that from time to time I have embellished the anecdotes that I include in these letters. Sometimes, I feel I need to make sure that you are paying attention. But this time, I am relating this story in its true, unvarnished state.

Two mature women with whom I am acquainted (No, one was not my wife!) had just finished their habitual Saturday morning walk through a wooded upper middle class neighborhood here in town. It was nine o’clock in the morning and the sun was shining. Suddenly, a mangy-looking fox trotted out of the woods and down the road toward them. Aware that from time to time local raccoons, skunks, and foxes have tested positive for rabies, these women began to run and flagged down the first car they saw, and without a word hopped in the back seat.

The surprised occupants of the vehicle were two mature men. You might call them strangers, but here in Maine, we don’t have any strangers. We have tourists. If a fellow Mainer doesn’t know you, he probably knows two people with whom you are acquainted.

As the women began to breathlessly explain their actions, one of the women felt a searing pain in her right thigh and assumed she had torn a muscle as she sprinted away from the fox. Within a few hundred yards, the car began to fill with smoke. Believing that the vehicle was on fire, all four occupants tumbled out into the street like four carnival clowns.

It quickly became clear that the cause of the smoke and the searing pain was that the woman’s pants were on fire. Throwing all caution and modesty to the wind, she quickly shed her pants in the middle of the road and in full view of these men, with whom it turns out she does share several acquaintances.

The source of the fire was the woman’s cell phone. The resulting injury was a palm-size, painful, deep, second-degree burn of her anterior thigh. In a quick Internet search, you will discover several very similar stories – minus the fox and the strangers. Some of the victims were children.

It turns out some cell phones have a tendency to spontaneously explode and/or catch fire. There seems to be no common factor in the events, although some of the ultrathin and flexible cell phones may be more prone to conflagration. However, the victim in our scenario has a storied past with cell phones. She has dropped them in the toilet at least once (history is a little unclear here on the exact number). On another occasion, she placed one in the sink of a public restroom, we can assume to prevent a second or third toilet submersion. As she approached the sink to retrieve it, the clever water-saving faucet – sensing her presence – turned itself on. But in the fox and fire incident, she denies any previous submersions or unusual events with this particular phone. A lawyer is now involved.

So while you and I as pediatricians may be concerned about the relationship between cell phones and health of our patients primarily because cell phones can be a dangerous distraction for young drivers, cyclists, and pedestrians, I share this anecdote to make you aware of another of their health hazards. You also may want to reconsider where you carry your cell phone.

I am not worried myself. I have a little flip phone for which I pay $100 for 500 minutes of usage a year, way more than I need or use. It couldn’t be considered a smartphone as its only noteworthy skill is taking pictures of the inside of my pants pocket. I suspect that its battery must be so small and impotent that even if it decides to self-immolate, I doubt I will notice. However, I do worry about scraggly-looking foxes meandering through my neighborhood.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.

Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.

©lokisurina/thinkstockphotos.com

“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”

She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.

Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.

“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.

Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.

Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:

• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.

• Chronic deep breast pain for 4 or more weeks.

• Failure of oral antifungals and or antibiotics.

Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.

“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”

Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.

Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.

Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.

“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.

Dr. Fullerton Stone had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.

Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.

©lokisurina/thinkstockphotos.com

“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”

She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.

Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.

“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.

Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.

Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:

• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.

• Chronic deep breast pain for 4 or more weeks.

• Failure of oral antifungals and or antibiotics.

Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.

“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”

Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.

Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.

Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.

“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.

Dr. Fullerton Stone had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.

Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.

©lokisurina/thinkstockphotos.com

“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”

She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.

Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.

“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.

Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.

Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:

• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.

• Chronic deep breast pain for 4 or more weeks.

• Failure of oral antifungals and or antibiotics.

Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.

“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”

Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.

Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.

Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.

“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.

Dr. Fullerton Stone had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

Q) At a lecture I recently attended, the speaker said sulfamethoxazole/trimethoprim is a potentially dangerous medication. I use it all the time. Is there any data to support her comments? Where did she get her information?

Sulfamethoxazole/trimethoprim (SMX/TMP) is a combination of two antibiotics, each of which has the potential to interact with other substances.

It is well documented that sulfamethoxazole can inhibit the metabolism of cytochrome P450 2C9 substrates. Frequently prescribed medications that also use the cytochrome substrate include warfarin and oral antihypoglycemic agents.

Trimethoprim’s distinct properties also lead to drug interactions. Trimethoprim inhibits sodium uptake by the appropriate channels in the distal tubule of the kidney, preventing reabsorption and altering the electrical balance of the tubular cells. As a result, the amount of potassium excreted into the urine is reduced, yielding an accumulation of serum potassium.¹

High serum potassium retention can manifest as hyperkalemia in patients with chronic kidney disease (CKD). Use of potassium-sparing drugs by patients with comorbidities, including CKD, can increase risk for hyperkalemia; concurrent use of these drugs with ACE inhibitors or angiotensin II receptor blockers (ARBs) compounds the risk.² The first reports of hyperkalemia with trimethoprim use occurred in HIV patients treated with large doses for Pneumocystis carinii infection.³

In a population-based case-control study, the results of which were published in the British Medical Journal, Fralick and colleagues analyzed data on older patients (age 66 or older) who were taking either ACE inhibitors or ARBs in combination with an antibiotic.⁴ They found a significantly increased risk for sudden death within seven days of prescription of SMX/TMP, compared to amoxicillin; a secondary analysis also revealed an increased risk for sudden death within 14 days with SMX/TMP. The researchers speculated that this excess risk, which translated to 3 sudden deaths in 1,000 patients taking SMX/TMP versus 1 sudden death in 1,000 patients taking amoxicillin, “reflects unrecognized arrhythmic death due to hyperkalemia.”

Since more than 250 million prescriptions for ACE inhibitors/ARBs and 20 million prescriptions for SMX/TMP are written each year, there will be instances of overlap. The prudent clinician would prescribe a different antibiotic or, if avoidance is not possible, use the lowest effective dose and duration of SMX/TMP. Close monitoring of serum potassium levels is warranted in patients with comorbidities, especially CKD, who are taking ACE inhibitors or ARBs—and of course, in our geriatric population. —DLC

Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

Q) At a lecture I recently attended, the speaker said sulfamethoxazole/trimethoprim is a potentially dangerous medication. I use it all the time. Is there any data to support her comments? Where did she get her information?

Sulfamethoxazole/trimethoprim (SMX/TMP) is a combination of two antibiotics, each of which has the potential to interact with other substances.

It is well documented that sulfamethoxazole can inhibit the metabolism of cytochrome P450 2C9 substrates. Frequently prescribed medications that also use the cytochrome substrate include warfarin and oral antihypoglycemic agents.

Trimethoprim’s distinct properties also lead to drug interactions. Trimethoprim inhibits sodium uptake by the appropriate channels in the distal tubule of the kidney, preventing reabsorption and altering the electrical balance of the tubular cells. As a result, the amount of potassium excreted into the urine is reduced, yielding an accumulation of serum potassium.¹

High serum potassium retention can manifest as hyperkalemia in patients with chronic kidney disease (CKD). Use of potassium-sparing drugs by patients with comorbidities, including CKD, can increase risk for hyperkalemia; concurrent use of these drugs with ACE inhibitors or angiotensin II receptor blockers (ARBs) compounds the risk.² The first reports of hyperkalemia with trimethoprim use occurred in HIV patients treated with large doses for Pneumocystis carinii infection.³

In a population-based case-control study, the results of which were published in the British Medical Journal, Fralick and colleagues analyzed data on older patients (age 66 or older) who were taking either ACE inhibitors or ARBs in combination with an antibiotic.⁴ They found a significantly increased risk for sudden death within seven days of prescription of SMX/TMP, compared to amoxicillin; a secondary analysis also revealed an increased risk for sudden death within 14 days with SMX/TMP. The researchers speculated that this excess risk, which translated to 3 sudden deaths in 1,000 patients taking SMX/TMP versus 1 sudden death in 1,000 patients taking amoxicillin, “reflects unrecognized arrhythmic death due to hyperkalemia.”

Since more than 250 million prescriptions for ACE inhibitors/ARBs and 20 million prescriptions for SMX/TMP are written each year, there will be instances of overlap. The prudent clinician would prescribe a different antibiotic or, if avoidance is not possible, use the lowest effective dose and duration of SMX/TMP. Close monitoring of serum potassium levels is warranted in patients with comorbidities, especially CKD, who are taking ACE inhibitors or ARBs—and of course, in our geriatric population. —DLC

Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

Q) At a lecture I recently attended, the speaker said sulfamethoxazole/trimethoprim is a potentially dangerous medication. I use it all the time. Is there any data to support her comments? Where did she get her information?

Sulfamethoxazole/trimethoprim (SMX/TMP) is a combination of two antibiotics, each of which has the potential to interact with other substances.

It is well documented that sulfamethoxazole can inhibit the metabolism of cytochrome P450 2C9 substrates. Frequently prescribed medications that also use the cytochrome substrate include warfarin and oral antihypoglycemic agents.

Trimethoprim’s distinct properties also lead to drug interactions. Trimethoprim inhibits sodium uptake by the appropriate channels in the distal tubule of the kidney, preventing reabsorption and altering the electrical balance of the tubular cells. As a result, the amount of potassium excreted into the urine is reduced, yielding an accumulation of serum potassium.¹

High serum potassium retention can manifest as hyperkalemia in patients with chronic kidney disease (CKD). Use of potassium-sparing drugs by patients with comorbidities, including CKD, can increase risk for hyperkalemia; concurrent use of these drugs with ACE inhibitors or angiotensin II receptor blockers (ARBs) compounds the risk.² The first reports of hyperkalemia with trimethoprim use occurred in HIV patients treated with large doses for Pneumocystis carinii infection.³

In a population-based case-control study, the results of which were published in the British Medical Journal, Fralick and colleagues analyzed data on older patients (age 66 or older) who were taking either ACE inhibitors or ARBs in combination with an antibiotic.⁴ They found a significantly increased risk for sudden death within seven days of prescription of SMX/TMP, compared to amoxicillin; a secondary analysis also revealed an increased risk for sudden death within 14 days with SMX/TMP. The researchers speculated that this excess risk, which translated to 3 sudden deaths in 1,000 patients taking SMX/TMP versus 1 sudden death in 1,000 patients taking amoxicillin, “reflects unrecognized arrhythmic death due to hyperkalemia.”

Since more than 250 million prescriptions for ACE inhibitors/ARBs and 20 million prescriptions for SMX/TMP are written each year, there will be instances of overlap. The prudent clinician would prescribe a different antibiotic or, if avoidance is not possible, use the lowest effective dose and duration of SMX/TMP. Close monitoring of serum potassium levels is warranted in patients with comorbidities, especially CKD, who are taking ACE inhibitors or ARBs—and of course, in our geriatric population. —DLC

Debra L. Coplon, DNP, DCC
City of Memphis Wellness Clinic, Tennessee

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

Infectious disease morbidity and mortality continue to disproportionately impact pregnant women and young infants.

In California, the incidence of pertussis approximates 100 cases per 100,000 in infants less than 5 months of age; a rate threefold greater than any other age group. Seven of nine (77%) deaths in 2013/2014 occurred in infants less than 3 months of age (California Department of Public Health Pertussis Report, Aug. 3, 2015).

Influenza severity and mortality is increased in pregnant women, and there is a greater risk of fetal morbidity and wastage. In the 2009 H₁N₁ pandemic, there was a 20% case fatality rate in women sick enough to be admitted to the ICU. The incidence of low birth weight also was increased among pregnant women delivering while hospitalized for influenza-related illness. These examples highlight the burden of vaccine-preventable disease in two vulnerable populations, pregnant women and infants too young to be protected by vaccines mandated by the U.S.immunization program.

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the Centers for Disease Control and Prevention, and many other national and state organizations endorse immunization of pregnant women to improve women’s and infants’ outcomes. Recent studies demonstrate that infants born to women vaccinated with influenza are 45%-48% less likely to be hospitalized for culture-proven influenza.

Benowitz et al. reported a 91.5% effectiveness for maternal influenza vaccination for prevention of hospitalization of infants caused by influenza in the first 6 months of life. The presumed mechanisms of protection are both the transplacental transfer of protective antibody as well as indirect protection from disease prevention in the mother (Clin Infect Dis. 2010 Dec 15;51(12):1355-61). The recommendation is that inactivated influenza vaccine can be given at any time during pregnancy; however, live attenuated influenza vaccine (LAIV; FluMist) is contraindicated, as are all live-virus vaccines. In contrast, Tdap is recommended for use either during pregnancy or post partum.

However, Healy et al. (Pediatr Infect Dis J. 2015;34(1):22-60) failed to demonstrate a benefit to postpartum immunization and cocooning for reducing pertussis illness in infants 6 months of age or younger. The likely explanation for this failure is revealed in a recent study in infant baboons where immunization with Tdap failed to decrease colonization or transmission of Bordetella pertussis, compared with natural disease or whole-cell pertussis. Thus, even though protective against disease, Tdap failure to prevent transmission within the community still occurs. The current Advisory Committee on Immunization Practices recommendation, immunization between 27 and 36 weeks, is designed to ensure high antibody concentrations in both mother and newborn at the time of birth and bridge the time period until infant immunization can elicit protective antibody.

The benefits achieved with maternal immunization must be weighed against potential for adverse events. There is no evidence of risk to either mother or infant from inactivated vaccines administered during pregnancy. Still, the recommendations for influenza and Tdap vaccine incorporate the high likelihood of exposure, the risk of morbidity or mortality from the infectious agent, and the likelihood of harm. During the H₁N₁ epidemic, a cohort study by Chambers et al. of H₁N₁ vaccine in exposed and unexposed pregnant women concluded that there was no increase in risk for major congenital defects, spontaneous abortion, or small for gestational age (Vaccine. 2013 Oct 17;31(44):5026-32). There was a signal for increase in prematurity, but the difference between H₁N₁-vaccinated and unvaccinated pregnancies was 3 days. In addition, a review of 11 studies, including one of 10,428 pregnant women, concluded there were no harmful maternal or fetal effects.

Additionally, no adverse risks have been identified in women who were inadvertently vaccinated during pregnancy with live-attenuated rubella, influenza, and yellow fever vaccines. Tetanus vaccination has been administered safely to several millions of pregnant women without documented serious adverse outcomes. Ongoing postmarketing surveillance continues as an important tool for identification of potential adverse effects.

One potential limitation is the blunting of infant immune responses to vaccination due to high serum antibody concentrations at the time of primary immunizations. Some studies have found lower antibody concentrations prior to booster vaccinations at 1 year of age. However, as morbidity and mortality is greater in the first months of life for many infectious diseases, this may be an acceptable trade off if high morbidity and mortality can be reduced in the first months of life.

Immunization during pregnancy represents only one aspect of prevention of vaccine preventable diseases. Preconception, prenatal, and postpartum visits with health care professionals represents an opportune time to discuss the benefits of immunization and their contribution to a healthy pregnancy outcome. Inactivated vaccines are safe for administration during pregnancy, live virus vaccines, despite being attenuated, are a theoretical risk if spread to the fetus occurs and therefore are contraindicated and should be administered during preconception counseling if indicated. The table below outlines vaccines that can be administered before, during, and after pregnancy.

Although once considered potentially contraindicated in pregnant women, evidence now supports specific vaccines as both safe for a pregnant woman and her fetus and effective for preventing serious disease in both. Universal immunization with influenza vaccine and Tdap, as recommended by multiple national professional medical organizations, will improve the outcome of pregnancy by prevention of morbidity and mortality from common community pathogens.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. E-mail him at [email protected].

Infectious disease morbidity and mortality continue to disproportionately impact pregnant women and young infants.

In California, the incidence of pertussis approximates 100 cases per 100,000 in infants less than 5 months of age; a rate threefold greater than any other age group. Seven of nine (77%) deaths in 2013/2014 occurred in infants less than 3 months of age (California Department of Public Health Pertussis Report, Aug. 3, 2015).

Influenza severity and mortality is increased in pregnant women, and there is a greater risk of fetal morbidity and wastage. In the 2009 H₁N₁ pandemic, there was a 20% case fatality rate in women sick enough to be admitted to the ICU. The incidence of low birth weight also was increased among pregnant women delivering while hospitalized for influenza-related illness. These examples highlight the burden of vaccine-preventable disease in two vulnerable populations, pregnant women and infants too young to be protected by vaccines mandated by the U.S.immunization program.

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the Centers for Disease Control and Prevention, and many other national and state organizations endorse immunization of pregnant women to improve women’s and infants’ outcomes. Recent studies demonstrate that infants born to women vaccinated with influenza are 45%-48% less likely to be hospitalized for culture-proven influenza.

Benowitz et al. reported a 91.5% effectiveness for maternal influenza vaccination for prevention of hospitalization of infants caused by influenza in the first 6 months of life. The presumed mechanisms of protection are both the transplacental transfer of protective antibody as well as indirect protection from disease prevention in the mother (Clin Infect Dis. 2010 Dec 15;51(12):1355-61). The recommendation is that inactivated influenza vaccine can be given at any time during pregnancy; however, live attenuated influenza vaccine (LAIV; FluMist) is contraindicated, as are all live-virus vaccines. In contrast, Tdap is recommended for use either during pregnancy or post partum.

However, Healy et al. (Pediatr Infect Dis J. 2015;34(1):22-60) failed to demonstrate a benefit to postpartum immunization and cocooning for reducing pertussis illness in infants 6 months of age or younger. The likely explanation for this failure is revealed in a recent study in infant baboons where immunization with Tdap failed to decrease colonization or transmission of Bordetella pertussis, compared with natural disease or whole-cell pertussis. Thus, even though protective against disease, Tdap failure to prevent transmission within the community still occurs. The current Advisory Committee on Immunization Practices recommendation, immunization between 27 and 36 weeks, is designed to ensure high antibody concentrations in both mother and newborn at the time of birth and bridge the time period until infant immunization can elicit protective antibody.

The benefits achieved with maternal immunization must be weighed against potential for adverse events. There is no evidence of risk to either mother or infant from inactivated vaccines administered during pregnancy. Still, the recommendations for influenza and Tdap vaccine incorporate the high likelihood of exposure, the risk of morbidity or mortality from the infectious agent, and the likelihood of harm. During the H₁N₁ epidemic, a cohort study by Chambers et al. of H₁N₁ vaccine in exposed and unexposed pregnant women concluded that there was no increase in risk for major congenital defects, spontaneous abortion, or small for gestational age (Vaccine. 2013 Oct 17;31(44):5026-32). There was a signal for increase in prematurity, but the difference between H₁N₁-vaccinated and unvaccinated pregnancies was 3 days. In addition, a review of 11 studies, including one of 10,428 pregnant women, concluded there were no harmful maternal or fetal effects.

Additionally, no adverse risks have been identified in women who were inadvertently vaccinated during pregnancy with live-attenuated rubella, influenza, and yellow fever vaccines. Tetanus vaccination has been administered safely to several millions of pregnant women without documented serious adverse outcomes. Ongoing postmarketing surveillance continues as an important tool for identification of potential adverse effects.

One potential limitation is the blunting of infant immune responses to vaccination due to high serum antibody concentrations at the time of primary immunizations. Some studies have found lower antibody concentrations prior to booster vaccinations at 1 year of age. However, as morbidity and mortality is greater in the first months of life for many infectious diseases, this may be an acceptable trade off if high morbidity and mortality can be reduced in the first months of life.

Immunization during pregnancy represents only one aspect of prevention of vaccine preventable diseases. Preconception, prenatal, and postpartum visits with health care professionals represents an opportune time to discuss the benefits of immunization and their contribution to a healthy pregnancy outcome. Inactivated vaccines are safe for administration during pregnancy, live virus vaccines, despite being attenuated, are a theoretical risk if spread to the fetus occurs and therefore are contraindicated and should be administered during preconception counseling if indicated. The table below outlines vaccines that can be administered before, during, and after pregnancy.

Although once considered potentially contraindicated in pregnant women, evidence now supports specific vaccines as both safe for a pregnant woman and her fetus and effective for preventing serious disease in both. Universal immunization with influenza vaccine and Tdap, as recommended by multiple national professional medical organizations, will improve the outcome of pregnancy by prevention of morbidity and mortality from common community pathogens.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. E-mail him at [email protected].

Infectious disease morbidity and mortality continue to disproportionately impact pregnant women and young infants.

In California, the incidence of pertussis approximates 100 cases per 100,000 in infants less than 5 months of age; a rate threefold greater than any other age group. Seven of nine (77%) deaths in 2013/2014 occurred in infants less than 3 months of age (California Department of Public Health Pertussis Report, Aug. 3, 2015).

Influenza severity and mortality is increased in pregnant women, and there is a greater risk of fetal morbidity and wastage. In the 2009 H₁N₁ pandemic, there was a 20% case fatality rate in women sick enough to be admitted to the ICU. The incidence of low birth weight also was increased among pregnant women delivering while hospitalized for influenza-related illness. These examples highlight the burden of vaccine-preventable disease in two vulnerable populations, pregnant women and infants too young to be protected by vaccines mandated by the U.S.immunization program.

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the Centers for Disease Control and Prevention, and many other national and state organizations endorse immunization of pregnant women to improve women’s and infants’ outcomes. Recent studies demonstrate that infants born to women vaccinated with influenza are 45%-48% less likely to be hospitalized for culture-proven influenza.

Benowitz et al. reported a 91.5% effectiveness for maternal influenza vaccination for prevention of hospitalization of infants caused by influenza in the first 6 months of life. The presumed mechanisms of protection are both the transplacental transfer of protective antibody as well as indirect protection from disease prevention in the mother (Clin Infect Dis. 2010 Dec 15;51(12):1355-61). The recommendation is that inactivated influenza vaccine can be given at any time during pregnancy; however, live attenuated influenza vaccine (LAIV; FluMist) is contraindicated, as are all live-virus vaccines. In contrast, Tdap is recommended for use either during pregnancy or post partum.

However, Healy et al. (Pediatr Infect Dis J. 2015;34(1):22-60) failed to demonstrate a benefit to postpartum immunization and cocooning for reducing pertussis illness in infants 6 months of age or younger. The likely explanation for this failure is revealed in a recent study in infant baboons where immunization with Tdap failed to decrease colonization or transmission of Bordetella pertussis, compared with natural disease or whole-cell pertussis. Thus, even though protective against disease, Tdap failure to prevent transmission within the community still occurs. The current Advisory Committee on Immunization Practices recommendation, immunization between 27 and 36 weeks, is designed to ensure high antibody concentrations in both mother and newborn at the time of birth and bridge the time period until infant immunization can elicit protective antibody.

The benefits achieved with maternal immunization must be weighed against potential for adverse events. There is no evidence of risk to either mother or infant from inactivated vaccines administered during pregnancy. Still, the recommendations for influenza and Tdap vaccine incorporate the high likelihood of exposure, the risk of morbidity or mortality from the infectious agent, and the likelihood of harm. During the H₁N₁ epidemic, a cohort study by Chambers et al. of H₁N₁ vaccine in exposed and unexposed pregnant women concluded that there was no increase in risk for major congenital defects, spontaneous abortion, or small for gestational age (Vaccine. 2013 Oct 17;31(44):5026-32). There was a signal for increase in prematurity, but the difference between H₁N₁-vaccinated and unvaccinated pregnancies was 3 days. In addition, a review of 11 studies, including one of 10,428 pregnant women, concluded there were no harmful maternal or fetal effects.

Additionally, no adverse risks have been identified in women who were inadvertently vaccinated during pregnancy with live-attenuated rubella, influenza, and yellow fever vaccines. Tetanus vaccination has been administered safely to several millions of pregnant women without documented serious adverse outcomes. Ongoing postmarketing surveillance continues as an important tool for identification of potential adverse effects.

One potential limitation is the blunting of infant immune responses to vaccination due to high serum antibody concentrations at the time of primary immunizations. Some studies have found lower antibody concentrations prior to booster vaccinations at 1 year of age. However, as morbidity and mortality is greater in the first months of life for many infectious diseases, this may be an acceptable trade off if high morbidity and mortality can be reduced in the first months of life.

Immunization during pregnancy represents only one aspect of prevention of vaccine preventable diseases. Preconception, prenatal, and postpartum visits with health care professionals represents an opportune time to discuss the benefits of immunization and their contribution to a healthy pregnancy outcome. Inactivated vaccines are safe for administration during pregnancy, live virus vaccines, despite being attenuated, are a theoretical risk if spread to the fetus occurs and therefore are contraindicated and should be administered during preconception counseling if indicated. The table below outlines vaccines that can be administered before, during, and after pregnancy.

Although once considered potentially contraindicated in pregnant women, evidence now supports specific vaccines as both safe for a pregnant woman and her fetus and effective for preventing serious disease in both. Universal immunization with influenza vaccine and Tdap, as recommended by multiple national professional medical organizations, will improve the outcome of pregnancy by prevention of morbidity and mortality from common community pathogens.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. E-mail him at [email protected].

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Aspirin tablets

Photo by Sage Ross

LONDON—Fatal bleeding is rare with extended dual antiplatelet therapy (DAPT), according to research presented at the ESC Congress 2015.

The study included patients with a coronary stent who were receiving 30 months or 12 months of DAPT to prevent stent thrombosis and major cardiovascular and cerebrovascular events.

The results showed that bleeding-related mortality accounted for a minority of deaths in both patient groups.

Laura Mauri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results as abstract 3916. The study, known as the DAPT trial, was funded by a consortium of 8 device and drug manufacturers and other entities.

The trial enrolled patients who were set to receive a drug-eluting or bare-metal stent. After stent placement, they received DAPT—aspirin plus thienopyridine (clopidogrel or prasugrel)—for at least 12 months.

After 12 months of therapy, patients who were treatment-compliant and event-free (no myocardial infarction, stroke, or moderate or severe bleeding) were randomized to continued thienopyridine or placebo, each in addition to aspirin, for an additional 18 months. At month 30, patients discontinued randomized treatment but remained on aspirin for 3 months.

Results from patients with drug-eluting stents were published in NEJM in 2014.

But Dr Mauri reported on causes of death in all 11,648 randomized patients. All deaths were reviewed and adjudicated by an independent committee of cardiologists and oncologists who were blinded to the randomized treatment groups.

Any death that was possibly, probably, or definitely related to any prior clinically evident bleeding event was adjudicated as “bleeding-related,” and any death that was possibly, probably, or definitely related to a malignancy or to complications from treatments specifically administered for the malignancy was adjudicated as “cancer-related.” Fatal bleeding was defined using the Bleeding Academic Research Consortium (BARC) definition.

All-cause mortality

At 30 months (end of the randomization period), the mortality rate was 1.9% in the 30-month treatment group and 1.5% in 12-month group (P=0.07).

There was no significant difference between the groups for cardiovascular mortality—both about 1% (P=0.97)—but there was a significant difference for non-cardiovascular mortality—0.9% and 0.5%, respectively (P=0.01).

At 33 months (combined randomization and aspirin monotherapy periods), the mortality rate was 2.2% in the 30-month treatment group and 1.8% in the 12-month treatment group (P=0.05).

The rates of cardiovascular mortality were 1.2% and 1.1%, respectively (P=0.51). And the rates of non-cardiovascular mortality were 1.0% and 0.7%, respectively (P=0.02).

Bleeding-related deaths

At 33 months, there was no significant difference in bleeding-related mortality. Fatal bleeding occurred in 0.3% of patients in the 30-month group and 0.2% of those in the 12-month group (P=0.36).

There was no significant difference between the groups for bleeding-related death without cancer or trauma (P>0.99), bleeding-related death with cancer (P=0.25), bleeding-related death with trauma (P=0.58), trauma-related death (P=0.30), or trauma-related death without bleeding (P=0.50).

“This analysis of the DAPT study provides valuable insight to suggest that fatal bleeding is rare with extended dual antiplatelet therapy and may be avoided with careful patient selection,” Dr Mauri said.

Cancer-related deaths

Dr Mauri noted that there was no significant difference in the incidence of cancer between the randomized groups (P=0.12). But there was a significant difference in the incidence of cancer-related mortality at 33 months. It was 0.6% in the 30-month group and 0.3% in the 12-month group (P=0.02).

However, when the investigators excluded the cancer-related deaths that occurred in patients whose cancer was diagnosed before they enrolled in the DAPT study, the difference in cancer-related death became non-significant (0.4% and 0.3%, respectively, P=0.16).

“Given the clear benefits of dual antiplatelet therapy in reducing myocardial infarction, these medications remain essential for patients with acute coronary syndromes or coronary stents,” Dr Mauri said. “The relationship with cancer requires further investigation.”

Aspirin tablets

Photo by Sage Ross

LONDON—Fatal bleeding is rare with extended dual antiplatelet therapy (DAPT), according to research presented at the ESC Congress 2015.

The study included patients with a coronary stent who were receiving 30 months or 12 months of DAPT to prevent stent thrombosis and major cardiovascular and cerebrovascular events.

The results showed that bleeding-related mortality accounted for a minority of deaths in both patient groups.

Laura Mauri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results as abstract 3916. The study, known as the DAPT trial, was funded by a consortium of 8 device and drug manufacturers and other entities.

The trial enrolled patients who were set to receive a drug-eluting or bare-metal stent. After stent placement, they received DAPT—aspirin plus thienopyridine (clopidogrel or prasugrel)—for at least 12 months.

After 12 months of therapy, patients who were treatment-compliant and event-free (no myocardial infarction, stroke, or moderate or severe bleeding) were randomized to continued thienopyridine or placebo, each in addition to aspirin, for an additional 18 months. At month 30, patients discontinued randomized treatment but remained on aspirin for 3 months.

Results from patients with drug-eluting stents were published in NEJM in 2014.

But Dr Mauri reported on causes of death in all 11,648 randomized patients. All deaths were reviewed and adjudicated by an independent committee of cardiologists and oncologists who were blinded to the randomized treatment groups.

Any death that was possibly, probably, or definitely related to any prior clinically evident bleeding event was adjudicated as “bleeding-related,” and any death that was possibly, probably, or definitely related to a malignancy or to complications from treatments specifically administered for the malignancy was adjudicated as “cancer-related.” Fatal bleeding was defined using the Bleeding Academic Research Consortium (BARC) definition.

All-cause mortality

At 30 months (end of the randomization period), the mortality rate was 1.9% in the 30-month treatment group and 1.5% in 12-month group (P=0.07).

There was no significant difference between the groups for cardiovascular mortality—both about 1% (P=0.97)—but there was a significant difference for non-cardiovascular mortality—0.9% and 0.5%, respectively (P=0.01).

At 33 months (combined randomization and aspirin monotherapy periods), the mortality rate was 2.2% in the 30-month treatment group and 1.8% in the 12-month treatment group (P=0.05).

The rates of cardiovascular mortality were 1.2% and 1.1%, respectively (P=0.51). And the rates of non-cardiovascular mortality were 1.0% and 0.7%, respectively (P=0.02).

Bleeding-related deaths

At 33 months, there was no significant difference in bleeding-related mortality. Fatal bleeding occurred in 0.3% of patients in the 30-month group and 0.2% of those in the 12-month group (P=0.36).

There was no significant difference between the groups for bleeding-related death without cancer or trauma (P>0.99), bleeding-related death with cancer (P=0.25), bleeding-related death with trauma (P=0.58), trauma-related death (P=0.30), or trauma-related death without bleeding (P=0.50).

“This analysis of the DAPT study provides valuable insight to suggest that fatal bleeding is rare with extended dual antiplatelet therapy and may be avoided with careful patient selection,” Dr Mauri said.

Cancer-related deaths

Dr Mauri noted that there was no significant difference in the incidence of cancer between the randomized groups (P=0.12). But there was a significant difference in the incidence of cancer-related mortality at 33 months. It was 0.6% in the 30-month group and 0.3% in the 12-month group (P=0.02).

However, when the investigators excluded the cancer-related deaths that occurred in patients whose cancer was diagnosed before they enrolled in the DAPT study, the difference in cancer-related death became non-significant (0.4% and 0.3%, respectively, P=0.16).

“Given the clear benefits of dual antiplatelet therapy in reducing myocardial infarction, these medications remain essential for patients with acute coronary syndromes or coronary stents,” Dr Mauri said. “The relationship with cancer requires further investigation.”

Aspirin tablets

Photo by Sage Ross

LONDON—Fatal bleeding is rare with extended dual antiplatelet therapy (DAPT), according to research presented at the ESC Congress 2015.

The study included patients with a coronary stent who were receiving 30 months or 12 months of DAPT to prevent stent thrombosis and major cardiovascular and cerebrovascular events.

The results showed that bleeding-related mortality accounted for a minority of deaths in both patient groups.

Laura Mauri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results as abstract 3916. The study, known as the DAPT trial, was funded by a consortium of 8 device and drug manufacturers and other entities.

The trial enrolled patients who were set to receive a drug-eluting or bare-metal stent. After stent placement, they received DAPT—aspirin plus thienopyridine (clopidogrel or prasugrel)—for at least 12 months.

After 12 months of therapy, patients who were treatment-compliant and event-free (no myocardial infarction, stroke, or moderate or severe bleeding) were randomized to continued thienopyridine or placebo, each in addition to aspirin, for an additional 18 months. At month 30, patients discontinued randomized treatment but remained on aspirin for 3 months.

Results from patients with drug-eluting stents were published in NEJM in 2014.

But Dr Mauri reported on causes of death in all 11,648 randomized patients. All deaths were reviewed and adjudicated by an independent committee of cardiologists and oncologists who were blinded to the randomized treatment groups.

Any death that was possibly, probably, or definitely related to any prior clinically evident bleeding event was adjudicated as “bleeding-related,” and any death that was possibly, probably, or definitely related to a malignancy or to complications from treatments specifically administered for the malignancy was adjudicated as “cancer-related.” Fatal bleeding was defined using the Bleeding Academic Research Consortium (BARC) definition.

All-cause mortality

At 30 months (end of the randomization period), the mortality rate was 1.9% in the 30-month treatment group and 1.5% in 12-month group (P=0.07).

There was no significant difference between the groups for cardiovascular mortality—both about 1% (P=0.97)—but there was a significant difference for non-cardiovascular mortality—0.9% and 0.5%, respectively (P=0.01).

At 33 months (combined randomization and aspirin monotherapy periods), the mortality rate was 2.2% in the 30-month treatment group and 1.8% in the 12-month treatment group (P=0.05).

The rates of cardiovascular mortality were 1.2% and 1.1%, respectively (P=0.51). And the rates of non-cardiovascular mortality were 1.0% and 0.7%, respectively (P=0.02).

Bleeding-related deaths

At 33 months, there was no significant difference in bleeding-related mortality. Fatal bleeding occurred in 0.3% of patients in the 30-month group and 0.2% of those in the 12-month group (P=0.36).

There was no significant difference between the groups for bleeding-related death without cancer or trauma (P>0.99), bleeding-related death with cancer (P=0.25), bleeding-related death with trauma (P=0.58), trauma-related death (P=0.30), or trauma-related death without bleeding (P=0.50).

“This analysis of the DAPT study provides valuable insight to suggest that fatal bleeding is rare with extended dual antiplatelet therapy and may be avoided with careful patient selection,” Dr Mauri said.

Cancer-related deaths

Dr Mauri noted that there was no significant difference in the incidence of cancer between the randomized groups (P=0.12). But there was a significant difference in the incidence of cancer-related mortality at 33 months. It was 0.6% in the 30-month group and 0.3% in the 12-month group (P=0.02).

However, when the investigators excluded the cancer-related deaths that occurred in patients whose cancer was diagnosed before they enrolled in the DAPT study, the difference in cancer-related death became non-significant (0.4% and 0.3%, respectively, P=0.16).

“Given the clear benefits of dual antiplatelet therapy in reducing myocardial infarction, these medications remain essential for patients with acute coronary syndromes or coronary stents,” Dr Mauri said. “The relationship with cancer requires further investigation.”

Thrombus

Image by Kevin MacKEnzie

LONDON—A score used to predict the risk of thromboembolic events, ischemic stroke, and death is only modestly accurate in patients with heart failure (HF), according to researchers.

They found the accuracy of the CHA2DS2-VASc score was dependent upon the endpoint being assessed and the duration of follow-up.

The score proved least effective for predicting thromboembolism, and its negative predictive values (NPVs) were inferior at 5 years of follow-up compared to 1 year.

Gregory Y. H Lip, MD, of Aalborg University in Denmark, and his colleagues reported these findings in JAMA and at the ESC Congress 2015 (abstract 1830*).

The team noted that the CHA2DS2-VASc score (congestive heart failure, hypertension, age 75 years or older [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior heart attack, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is already used clinically for stroke risk stratification in patients with atrial fibrillation (AF).

But its usefulness in a population of patients with HF has been unclear. So the researchers investigated whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in patients with a new diagnosis of HF, with or without AF.

Using Danish registries, the researchers compiled data from 42,987 patients (22% with concomitant AF). The patients were not receiving anticoagulation and had been diagnosed with new-onset HF from 2000 to 2012.

The end of follow-up was December 31, 2012. Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk) were stratified by the presence of AF at study entry.

Among patients without AF, the incidence of thromboembolism was 3.5%, the rate of ischemic stroke was 1%, and the death rate was 7.2%. Among patients with AF, the rates were 4.2%, 2%, and 13.2%, respectively.

Predictive accuracy

For predicting thromboembolism in patients without AF, the C statistics were 0.63 at 1 year and 0.67 at 5 years. The NPVs were 88% and 73%, respectively.

For predicting thromboembolism in patients with AF, the C statistics were 0.62 at 1 year and 0.69 at 5 years. The NPVs were 88% and 61%, respectively.

For predicting ischemic stroke in patients without AF, the C statistics were 0.67 at 1 year and 0.69 at 5 years. The NPVs were 92% and 78%, respectively.

For predicting ischemic stroke in patients with AF, the C statistics were 0.64 at 1 year and 0.71 at 5 years. The NPVs were 91% and 69%, respectively.

For predicting death in patients without AF, the C statistics were 0.64 at 1 year and 0.68 at 5 years. The NPVs were 93% and 81%, respectively.

For predicting death in patients with AF, the C statistics were 0.63 at 1 year and 0.70 at 5 years. The NPVs were 94% and 76%, respectively.

Based on these results, the researchers said the clinical usefulness of the CHA2DS2-VASc score for patients with HF remains to be determined. And preventative strategies to reduce thromboembolism and ischemic stroke among these patients require further investigation.

*Information in the abstract differs from that presented.

Thrombus

Image by Kevin MacKEnzie

LONDON—A score used to predict the risk of thromboembolic events, ischemic stroke, and death is only modestly accurate in patients with heart failure (HF), according to researchers.

They found the accuracy of the CHA2DS2-VASc score was dependent upon the endpoint being assessed and the duration of follow-up.

The score proved least effective for predicting thromboembolism, and its negative predictive values (NPVs) were inferior at 5 years of follow-up compared to 1 year.

Gregory Y. H Lip, MD, of Aalborg University in Denmark, and his colleagues reported these findings in JAMA and at the ESC Congress 2015 (abstract 1830*).

The team noted that the CHA2DS2-VASc score (congestive heart failure, hypertension, age 75 years or older [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior heart attack, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is already used clinically for stroke risk stratification in patients with atrial fibrillation (AF).

But its usefulness in a population of patients with HF has been unclear. So the researchers investigated whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in patients with a new diagnosis of HF, with or without AF.

Using Danish registries, the researchers compiled data from 42,987 patients (22% with concomitant AF). The patients were not receiving anticoagulation and had been diagnosed with new-onset HF from 2000 to 2012.

The end of follow-up was December 31, 2012. Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk) were stratified by the presence of AF at study entry.

Among patients without AF, the incidence of thromboembolism was 3.5%, the rate of ischemic stroke was 1%, and the death rate was 7.2%. Among patients with AF, the rates were 4.2%, 2%, and 13.2%, respectively.

Predictive accuracy

For predicting thromboembolism in patients without AF, the C statistics were 0.63 at 1 year and 0.67 at 5 years. The NPVs were 88% and 73%, respectively.

For predicting thromboembolism in patients with AF, the C statistics were 0.62 at 1 year and 0.69 at 5 years. The NPVs were 88% and 61%, respectively.

For predicting ischemic stroke in patients without AF, the C statistics were 0.67 at 1 year and 0.69 at 5 years. The NPVs were 92% and 78%, respectively.

For predicting ischemic stroke in patients with AF, the C statistics were 0.64 at 1 year and 0.71 at 5 years. The NPVs were 91% and 69%, respectively.

For predicting death in patients without AF, the C statistics were 0.64 at 1 year and 0.68 at 5 years. The NPVs were 93% and 81%, respectively.

For predicting death in patients with AF, the C statistics were 0.63 at 1 year and 0.70 at 5 years. The NPVs were 94% and 76%, respectively.

Based on these results, the researchers said the clinical usefulness of the CHA2DS2-VASc score for patients with HF remains to be determined. And preventative strategies to reduce thromboembolism and ischemic stroke among these patients require further investigation.

*Information in the abstract differs from that presented.

Thrombus

Image by Kevin MacKEnzie

LONDON—A score used to predict the risk of thromboembolic events, ischemic stroke, and death is only modestly accurate in patients with heart failure (HF), according to researchers.

They found the accuracy of the CHA2DS2-VASc score was dependent upon the endpoint being assessed and the duration of follow-up.

The score proved least effective for predicting thromboembolism, and its negative predictive values (NPVs) were inferior at 5 years of follow-up compared to 1 year.

Gregory Y. H Lip, MD, of Aalborg University in Denmark, and his colleagues reported these findings in JAMA and at the ESC Congress 2015 (abstract 1830*).

The team noted that the CHA2DS2-VASc score (congestive heart failure, hypertension, age 75 years or older [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior heart attack, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is already used clinically for stroke risk stratification in patients with atrial fibrillation (AF).

But its usefulness in a population of patients with HF has been unclear. So the researchers investigated whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in patients with a new diagnosis of HF, with or without AF.

Using Danish registries, the researchers compiled data from 42,987 patients (22% with concomitant AF). The patients were not receiving anticoagulation and had been diagnosed with new-onset HF from 2000 to 2012.

The end of follow-up was December 31, 2012. Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk) were stratified by the presence of AF at study entry.

Among patients without AF, the incidence of thromboembolism was 3.5%, the rate of ischemic stroke was 1%, and the death rate was 7.2%. Among patients with AF, the rates were 4.2%, 2%, and 13.2%, respectively.

Predictive accuracy

For predicting thromboembolism in patients without AF, the C statistics were 0.63 at 1 year and 0.67 at 5 years. The NPVs were 88% and 73%, respectively.

For predicting thromboembolism in patients with AF, the C statistics were 0.62 at 1 year and 0.69 at 5 years. The NPVs were 88% and 61%, respectively.

For predicting ischemic stroke in patients without AF, the C statistics were 0.67 at 1 year and 0.69 at 5 years. The NPVs were 92% and 78%, respectively.

For predicting ischemic stroke in patients with AF, the C statistics were 0.64 at 1 year and 0.71 at 5 years. The NPVs were 91% and 69%, respectively.

For predicting death in patients without AF, the C statistics were 0.64 at 1 year and 0.68 at 5 years. The NPVs were 93% and 81%, respectively.

For predicting death in patients with AF, the C statistics were 0.63 at 1 year and 0.70 at 5 years. The NPVs were 94% and 76%, respectively.

Based on these results, the researchers said the clinical usefulness of the CHA2DS2-VASc score for patients with HF remains to be determined. And preventative strategies to reduce thromboembolism and ischemic stroke among these patients require further investigation.

*Information in the abstract differs from that presented.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

LONDON—Immune cells may represent an important therapeutic target for preventing stent thrombosis, according to investigators from the PRESTIGE study.

The team analyzed more than 250 thrombus specimens and observed leukocyte infiltration in the context of early and late stent thrombosis.

Neutrophils were the most common leukocyte detected, and eosinophils were present in thrombi from all stent types.

The investigators reported these findings in the European Heart Journal and at the ESC Congress 2015 (abstract 1996*).

“Our results suggest that immune-cell-mediated thrombotic processes may be a realistic target for novel therapies to prevent [stent thrombosis],” said study investigator Steffen Massberg, PhD, of Ludwig-Maximilians University in Munich, Germany.

“Inhibition of triggers, such as extracellular nucleic acids activating the contact phase, may not only result in efficient anticoagulation in the setting of [stent thrombosis] but might also yield less therapy-associated bleeding. Future studies should evaluate whether inhibition of immune-cell-driven thrombotic pathways are effective and safe in clinical practice.”

The PRESTIGE study included patients with stent thrombosis who underwent thrombus aspiration at 9 centers in Europe between 2010 and 2014. In all, the investigators analyzed 253 thrombus specimens from these patients.

Seventy-nine specimens (31.2%) were from patients presenting with early stent thrombosis, and 174 (68.8%) were from patients with late stent thrombosis. Seventy-nine (31.2%) were from bare metal stents, 166 (65.6%) were from drug-eluting stents, and 8 (3.2%) were from stents of unknown type.

The thrombus specimens had heterogeneous morphology, with platelet-rich thrombus and fibrin/fibrinogen fragments being most abundant.

The investigators said leukocyte infiltrations were hallmarks of both early and late stent thrombosis, with neutrophils representing the most prominent subset. Neutrophils were found in similar amounts in early and late stent thrombosis.

“It is important to note that leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction,” Dr Massberg said.

He and his colleagues also observed neutrophil extracellular traps (NETs) in 23% of samples.

And they found that eosinophils were present in all stent types, but there were higher numbers in patients with late stent thrombosis in sirolimus-eluting and everolimus-eluting stents.

“The presence of NETs supports their pathophysiological relevance in [stent thrombosis], while eosinophil recruitment suggests an allergic component to the process of [stent thrombosis],” Dr Massberg said.

*Information in the abstract differs from that presented.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

LONDON—Immune cells may represent an important therapeutic target for preventing stent thrombosis, according to investigators from the PRESTIGE study.

The team analyzed more than 250 thrombus specimens and observed leukocyte infiltration in the context of early and late stent thrombosis.

Neutrophils were the most common leukocyte detected, and eosinophils were present in thrombi from all stent types.

The investigators reported these findings in the European Heart Journal and at the ESC Congress 2015 (abstract 1996*).

“Our results suggest that immune-cell-mediated thrombotic processes may be a realistic target for novel therapies to prevent [stent thrombosis],” said study investigator Steffen Massberg, PhD, of Ludwig-Maximilians University in Munich, Germany.

“Inhibition of triggers, such as extracellular nucleic acids activating the contact phase, may not only result in efficient anticoagulation in the setting of [stent thrombosis] but might also yield less therapy-associated bleeding. Future studies should evaluate whether inhibition of immune-cell-driven thrombotic pathways are effective and safe in clinical practice.”

The PRESTIGE study included patients with stent thrombosis who underwent thrombus aspiration at 9 centers in Europe between 2010 and 2014. In all, the investigators analyzed 253 thrombus specimens from these patients.

Seventy-nine specimens (31.2%) were from patients presenting with early stent thrombosis, and 174 (68.8%) were from patients with late stent thrombosis. Seventy-nine (31.2%) were from bare metal stents, 166 (65.6%) were from drug-eluting stents, and 8 (3.2%) were from stents of unknown type.

The thrombus specimens had heterogeneous morphology, with platelet-rich thrombus and fibrin/fibrinogen fragments being most abundant.

The investigators said leukocyte infiltrations were hallmarks of both early and late stent thrombosis, with neutrophils representing the most prominent subset. Neutrophils were found in similar amounts in early and late stent thrombosis.

“It is important to note that leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction,” Dr Massberg said.

He and his colleagues also observed neutrophil extracellular traps (NETs) in 23% of samples.

And they found that eosinophils were present in all stent types, but there were higher numbers in patients with late stent thrombosis in sirolimus-eluting and everolimus-eluting stents.

“The presence of NETs supports their pathophysiological relevance in [stent thrombosis], while eosinophil recruitment suggests an allergic component to the process of [stent thrombosis],” Dr Massberg said.

*Information in the abstract differs from that presented.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

LONDON—Immune cells may represent an important therapeutic target for preventing stent thrombosis, according to investigators from the PRESTIGE study.

The team analyzed more than 250 thrombus specimens and observed leukocyte infiltration in the context of early and late stent thrombosis.

Neutrophils were the most common leukocyte detected, and eosinophils were present in thrombi from all stent types.

The investigators reported these findings in the European Heart Journal and at the ESC Congress 2015 (abstract 1996*).

“Our results suggest that immune-cell-mediated thrombotic processes may be a realistic target for novel therapies to prevent [stent thrombosis],” said study investigator Steffen Massberg, PhD, of Ludwig-Maximilians University in Munich, Germany.

“Inhibition of triggers, such as extracellular nucleic acids activating the contact phase, may not only result in efficient anticoagulation in the setting of [stent thrombosis] but might also yield less therapy-associated bleeding. Future studies should evaluate whether inhibition of immune-cell-driven thrombotic pathways are effective and safe in clinical practice.”

The PRESTIGE study included patients with stent thrombosis who underwent thrombus aspiration at 9 centers in Europe between 2010 and 2014. In all, the investigators analyzed 253 thrombus specimens from these patients.

Seventy-nine specimens (31.2%) were from patients presenting with early stent thrombosis, and 174 (68.8%) were from patients with late stent thrombosis. Seventy-nine (31.2%) were from bare metal stents, 166 (65.6%) were from drug-eluting stents, and 8 (3.2%) were from stents of unknown type.

The thrombus specimens had heterogeneous morphology, with platelet-rich thrombus and fibrin/fibrinogen fragments being most abundant.

The investigators said leukocyte infiltrations were hallmarks of both early and late stent thrombosis, with neutrophils representing the most prominent subset. Neutrophils were found in similar amounts in early and late stent thrombosis.

“It is important to note that leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction,” Dr Massberg said.

He and his colleagues also observed neutrophil extracellular traps (NETs) in 23% of samples.

And they found that eosinophils were present in all stent types, but there were higher numbers in patients with late stent thrombosis in sirolimus-eluting and everolimus-eluting stents.

“The presence of NETs supports their pathophysiological relevance in [stent thrombosis], while eosinophil recruitment suggests an allergic component to the process of [stent thrombosis],” Dr Massberg said.

*Information in the abstract differs from that presented.