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Vitamin D deficiency linked to hepatitis B infection
More than half of hepatitis B patients were vitamin D deficient, and deficiency was associated with worse outcomes, in a Vietnamese study published in BMC Infectious Diseases.
A total of 48% of 165 chronic hepatitis B patients, 54% of 127 hepatitis B virus (HBV)-associated cirrhosis patients, and 55% of 108 virus-associated hepatocellular carcinoma (HCC) patients had levels below 20 ng/mL, compared with 33% of 122 healthy controls.
Vitamin D levels inversely correlated with viral DNA loads, and lower levels were associated with more severe cirrhosis. On multivariate analyses adjusted for age and sex, HBV infection was an independent risk factor for vitamin D inadequacy (BMC Infect Dis. 2016 Sep 23;16[1]:507).
“These findings suggest that serum vitamin D levels contribute significantly to the clinical courses of HBV infection, including the severe consequences of” cirrhosis and HCC. “Our findings allow speculating that vitamin D and its analogs might provide a potential therapeutic addendum in the treatment of chronic liver diseases,” concluded investigators led by Nghiem Xuan Hoan, MD, of the Vietnamese-German Center for Medical Research in Hanoi.
Total vitamin D (25[OH] D2 and D3) levels were measured only once in the study; the cross-sectional design meant that “we could not determine the fluctuation of vitamin D levels over the course of HBV infection as well as the causative association of vitamin D levels and HBV-related liver diseases,” the researchers explained.
Low levels could be caused by impaired hepatic function, because the liver is key to vitamin D metabolism. HBV patients also tended to be older than the healthy controls were, which also might have contributed to the greater likelihood of deficiency.
Even so, a case seems to be building that vitamin D has an active role in HBV liver disease. Other investigations also have found an inverse relationship between viral loads and vitamin D status, and low levels previously have been associated with HCC.
Vitamin D is involved in adaptive and innate immune responses that clear the virus and other infections from the body, or at least keep them in check. Deficiency has been associated with susceptibility to various infections and inflammatory diseases, as well as carcinogenesis.
There was no industry funding for the work, and the authors had no disclosures.
More than half of hepatitis B patients were vitamin D deficient, and deficiency was associated with worse outcomes, in a Vietnamese study published in BMC Infectious Diseases.
A total of 48% of 165 chronic hepatitis B patients, 54% of 127 hepatitis B virus (HBV)-associated cirrhosis patients, and 55% of 108 virus-associated hepatocellular carcinoma (HCC) patients had levels below 20 ng/mL, compared with 33% of 122 healthy controls.
Vitamin D levels inversely correlated with viral DNA loads, and lower levels were associated with more severe cirrhosis. On multivariate analyses adjusted for age and sex, HBV infection was an independent risk factor for vitamin D inadequacy (BMC Infect Dis. 2016 Sep 23;16[1]:507).
“These findings suggest that serum vitamin D levels contribute significantly to the clinical courses of HBV infection, including the severe consequences of” cirrhosis and HCC. “Our findings allow speculating that vitamin D and its analogs might provide a potential therapeutic addendum in the treatment of chronic liver diseases,” concluded investigators led by Nghiem Xuan Hoan, MD, of the Vietnamese-German Center for Medical Research in Hanoi.
Total vitamin D (25[OH] D2 and D3) levels were measured only once in the study; the cross-sectional design meant that “we could not determine the fluctuation of vitamin D levels over the course of HBV infection as well as the causative association of vitamin D levels and HBV-related liver diseases,” the researchers explained.
Low levels could be caused by impaired hepatic function, because the liver is key to vitamin D metabolism. HBV patients also tended to be older than the healthy controls were, which also might have contributed to the greater likelihood of deficiency.
Even so, a case seems to be building that vitamin D has an active role in HBV liver disease. Other investigations also have found an inverse relationship between viral loads and vitamin D status, and low levels previously have been associated with HCC.
Vitamin D is involved in adaptive and innate immune responses that clear the virus and other infections from the body, or at least keep them in check. Deficiency has been associated with susceptibility to various infections and inflammatory diseases, as well as carcinogenesis.
There was no industry funding for the work, and the authors had no disclosures.
More than half of hepatitis B patients were vitamin D deficient, and deficiency was associated with worse outcomes, in a Vietnamese study published in BMC Infectious Diseases.
A total of 48% of 165 chronic hepatitis B patients, 54% of 127 hepatitis B virus (HBV)-associated cirrhosis patients, and 55% of 108 virus-associated hepatocellular carcinoma (HCC) patients had levels below 20 ng/mL, compared with 33% of 122 healthy controls.
Vitamin D levels inversely correlated with viral DNA loads, and lower levels were associated with more severe cirrhosis. On multivariate analyses adjusted for age and sex, HBV infection was an independent risk factor for vitamin D inadequacy (BMC Infect Dis. 2016 Sep 23;16[1]:507).
“These findings suggest that serum vitamin D levels contribute significantly to the clinical courses of HBV infection, including the severe consequences of” cirrhosis and HCC. “Our findings allow speculating that vitamin D and its analogs might provide a potential therapeutic addendum in the treatment of chronic liver diseases,” concluded investigators led by Nghiem Xuan Hoan, MD, of the Vietnamese-German Center for Medical Research in Hanoi.
Total vitamin D (25[OH] D2 and D3) levels were measured only once in the study; the cross-sectional design meant that “we could not determine the fluctuation of vitamin D levels over the course of HBV infection as well as the causative association of vitamin D levels and HBV-related liver diseases,” the researchers explained.
Low levels could be caused by impaired hepatic function, because the liver is key to vitamin D metabolism. HBV patients also tended to be older than the healthy controls were, which also might have contributed to the greater likelihood of deficiency.
Even so, a case seems to be building that vitamin D has an active role in HBV liver disease. Other investigations also have found an inverse relationship between viral loads and vitamin D status, and low levels previously have been associated with HCC.
Vitamin D is involved in adaptive and innate immune responses that clear the virus and other infections from the body, or at least keep them in check. Deficiency has been associated with susceptibility to various infections and inflammatory diseases, as well as carcinogenesis.
There was no industry funding for the work, and the authors had no disclosures.
FROM BMC INFECTIOUS DISEASES
Asleep deep brain stimulation placement offers advantages in Parkinson’s
PORTLAND, ORE. – Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.
Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”
Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.
Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).
Better language measures with asleep DBS
Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.
Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.
Patients tolerated asleep DBS well, and there were no serious complications.
The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”
Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.
Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”
Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”
“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”
Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”
In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.
“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”
Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.
PORTLAND, ORE. – Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.
Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”
Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.
Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).
Better language measures with asleep DBS
Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.
Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.
Patients tolerated asleep DBS well, and there were no serious complications.
The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”
Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.
Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”
Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”
“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”
Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”
In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.
“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”
Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.
PORTLAND, ORE. – Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.
Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”
Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.
Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).
Better language measures with asleep DBS
Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.
Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.
Patients tolerated asleep DBS well, and there were no serious complications.
The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”
Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.
Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”
Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”
“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”
Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”
In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.
“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”
Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.
AT WPC 2016
Key clinical point:
Major finding: The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.
Data source: Prospective, open-label study of 64 patients receiving either awake or asleep deep brain stimulation placement.
Disclosures: Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.
Acne and diet: Still no solid basis for dietary recommendations
BOSTON – For years, much of the information that has circulated about the relationship of diet to acne has been inconsistent. And while recent studies have pointed to two aggravating factors – foods with a high glycemic index and skim milk – whether dietary changes can help control acne remains up in the air, according to Andrea Zaenglein, MD.
At the American Academy of Dermatology summer meeting, Dr. Zaenglein, professor of dermatology and pediatrics, Penn State University, Hershey, reviewed information about diet and acne dating back to the early 1930s, when reports suggested an increased risk of acne in people who were glucose intolerant. Subsequent studies looked at the role of dairy, carbohydrate, chloride, saturated and total fats, sugar, and chocolate in acne. Researchers found no acne in a study of natives of Kitava, an island in Papua New Guinea, whose diet consisted mostly of roots, coconut, fruit, and fish (Arch Dermatol. 2002;138[12]:1584-90). But genetics certainly appears to play a dominant role in acne, Dr. Zaenglein said, referring to a large twin study that found that in 81% of the population with acne, it was due to genetic factors, and in 19% it was due to environmental factors (J Invest Dermatol. 2002 Dec;119[6]:1317-22).
For now, Dr. Zaenglein’s advice is to recommend a low glycemic index diet mainly of fruits and vegetables and low in saturated fats and sugars, which may ameliorate acne by decreasing weight and insulin resistance – especially in patients who already have abnormal metabolic parameters. Patients should also be advised to limit processed foods, meat, and dairy, she added.
As far as dairy and acne, it is too early to say what the impact of intervention would be “because we don’t have any great interventional studies that have been done,” she said. Moreover, it is unclear how early dietary interventions would need to be started to reduce an individual’s risk of acne, she added.“It could go all the way back to things that happened when you were born that influence your outcome,” Dr. Zaenglein said. For example, babies born prematurely are at greater risk for endocrine stressors, which lead to premature adrenarche, increasing their risk for acne, she noted.
“We really need new, better intervention studies to be able to give advice to our patients,” she said. However, conducting such studies is challenging because it is difficult for people to eliminate dairy or other types of food from their diets for a prolonged period. To date, the majority of dietary studies have been observational and have relied on subjects’ recall of what they consumed, so these studies have their own inherent problems, she added.Dr. Zaenglein’s disclosures include serving as an adviser to Anacor Pharmaceuticals and Valeant Pharmaceuticals International, and serving as an investigator and receiving grants/research funding from Anacor, Astellas Pharma US, Ranbaxy Laboratories Limited, and Stiefel, a GSK company.
BOSTON – For years, much of the information that has circulated about the relationship of diet to acne has been inconsistent. And while recent studies have pointed to two aggravating factors – foods with a high glycemic index and skim milk – whether dietary changes can help control acne remains up in the air, according to Andrea Zaenglein, MD.
At the American Academy of Dermatology summer meeting, Dr. Zaenglein, professor of dermatology and pediatrics, Penn State University, Hershey, reviewed information about diet and acne dating back to the early 1930s, when reports suggested an increased risk of acne in people who were glucose intolerant. Subsequent studies looked at the role of dairy, carbohydrate, chloride, saturated and total fats, sugar, and chocolate in acne. Researchers found no acne in a study of natives of Kitava, an island in Papua New Guinea, whose diet consisted mostly of roots, coconut, fruit, and fish (Arch Dermatol. 2002;138[12]:1584-90). But genetics certainly appears to play a dominant role in acne, Dr. Zaenglein said, referring to a large twin study that found that in 81% of the population with acne, it was due to genetic factors, and in 19% it was due to environmental factors (J Invest Dermatol. 2002 Dec;119[6]:1317-22).
For now, Dr. Zaenglein’s advice is to recommend a low glycemic index diet mainly of fruits and vegetables and low in saturated fats and sugars, which may ameliorate acne by decreasing weight and insulin resistance – especially in patients who already have abnormal metabolic parameters. Patients should also be advised to limit processed foods, meat, and dairy, she added.
As far as dairy and acne, it is too early to say what the impact of intervention would be “because we don’t have any great interventional studies that have been done,” she said. Moreover, it is unclear how early dietary interventions would need to be started to reduce an individual’s risk of acne, she added.“It could go all the way back to things that happened when you were born that influence your outcome,” Dr. Zaenglein said. For example, babies born prematurely are at greater risk for endocrine stressors, which lead to premature adrenarche, increasing their risk for acne, she noted.
“We really need new, better intervention studies to be able to give advice to our patients,” she said. However, conducting such studies is challenging because it is difficult for people to eliminate dairy or other types of food from their diets for a prolonged period. To date, the majority of dietary studies have been observational and have relied on subjects’ recall of what they consumed, so these studies have their own inherent problems, she added.Dr. Zaenglein’s disclosures include serving as an adviser to Anacor Pharmaceuticals and Valeant Pharmaceuticals International, and serving as an investigator and receiving grants/research funding from Anacor, Astellas Pharma US, Ranbaxy Laboratories Limited, and Stiefel, a GSK company.
BOSTON – For years, much of the information that has circulated about the relationship of diet to acne has been inconsistent. And while recent studies have pointed to two aggravating factors – foods with a high glycemic index and skim milk – whether dietary changes can help control acne remains up in the air, according to Andrea Zaenglein, MD.
At the American Academy of Dermatology summer meeting, Dr. Zaenglein, professor of dermatology and pediatrics, Penn State University, Hershey, reviewed information about diet and acne dating back to the early 1930s, when reports suggested an increased risk of acne in people who were glucose intolerant. Subsequent studies looked at the role of dairy, carbohydrate, chloride, saturated and total fats, sugar, and chocolate in acne. Researchers found no acne in a study of natives of Kitava, an island in Papua New Guinea, whose diet consisted mostly of roots, coconut, fruit, and fish (Arch Dermatol. 2002;138[12]:1584-90). But genetics certainly appears to play a dominant role in acne, Dr. Zaenglein said, referring to a large twin study that found that in 81% of the population with acne, it was due to genetic factors, and in 19% it was due to environmental factors (J Invest Dermatol. 2002 Dec;119[6]:1317-22).
For now, Dr. Zaenglein’s advice is to recommend a low glycemic index diet mainly of fruits and vegetables and low in saturated fats and sugars, which may ameliorate acne by decreasing weight and insulin resistance – especially in patients who already have abnormal metabolic parameters. Patients should also be advised to limit processed foods, meat, and dairy, she added.
As far as dairy and acne, it is too early to say what the impact of intervention would be “because we don’t have any great interventional studies that have been done,” she said. Moreover, it is unclear how early dietary interventions would need to be started to reduce an individual’s risk of acne, she added.“It could go all the way back to things that happened when you were born that influence your outcome,” Dr. Zaenglein said. For example, babies born prematurely are at greater risk for endocrine stressors, which lead to premature adrenarche, increasing their risk for acne, she noted.
“We really need new, better intervention studies to be able to give advice to our patients,” she said. However, conducting such studies is challenging because it is difficult for people to eliminate dairy or other types of food from their diets for a prolonged period. To date, the majority of dietary studies have been observational and have relied on subjects’ recall of what they consumed, so these studies have their own inherent problems, she added.Dr. Zaenglein’s disclosures include serving as an adviser to Anacor Pharmaceuticals and Valeant Pharmaceuticals International, and serving as an investigator and receiving grants/research funding from Anacor, Astellas Pharma US, Ranbaxy Laboratories Limited, and Stiefel, a GSK company.
Perinatal problems raise adult OCD risk
Adverse events during the perinatal period were independently associated with an increased risk of obsessive-compulsive disorder at age 40 years, based on data published Oct. 5 from a population-based cohort study of more than 2 million Swedish children.
Perinatal complications, including C-section delivery and preterm birth, have been linked to psychiatric disorders including schizophrenia, autism, and attention-deficit/hyperactivity disorder, but evidence of an impact of obsessive-compulsive disorders has not been well studied, reported Gustaf Brander of the Karolinska Institutet, Stockholm, and his colleagues.
The researchers reviewed data from 2,421,284 live singleton births in Sweden between Jan. 1, 1973, and Dec. 31, 1996. The overall prevalence of OCD was 1.3% at 40 years of age. Several perinatal factors were independently associated with an increased OCD risk: breech presentation, cesarean section delivery, gestational age of less than 32 weeks, maternal smoking during pregnancy, Apgar scores near the distress level, and both low and high birth weight (defined as 1,500-2,500 g and greater than 4,500 g, respectively).
“These findings contradict the widely held notion that, although mental disorders share genetic risk factors, the contribution of environmental risk factors is largely disorder specific,” with the exception of maternal smoking during pregnancy, the researchers wrote. In addition, the researchers found a dose-response relationship in which the risk for OCD increased with the greater number of perinatal adverse events.
“The findings are important for the understanding of the cause of OCD and will inform future studies of gene by environment interaction and epigenetics,” the researchers said. “If the finding is replication, the association between maternal smoking during pregnancy and OCD may emerge as an interesting disorder-specific risk factor for evaluation in future research,” they added.
Mr. Brander had no financial conflicts to disclose; several coauthors disclosed relationships with companies including Eli Lilly, Shire, and Medice.
Find the full study here: (JAMA Psychiatry. 2016 Oct 5. doi: 10.1001/jamapsychiatry.2016.2095).
Adverse events during the perinatal period were independently associated with an increased risk of obsessive-compulsive disorder at age 40 years, based on data published Oct. 5 from a population-based cohort study of more than 2 million Swedish children.
Perinatal complications, including C-section delivery and preterm birth, have been linked to psychiatric disorders including schizophrenia, autism, and attention-deficit/hyperactivity disorder, but evidence of an impact of obsessive-compulsive disorders has not been well studied, reported Gustaf Brander of the Karolinska Institutet, Stockholm, and his colleagues.
The researchers reviewed data from 2,421,284 live singleton births in Sweden between Jan. 1, 1973, and Dec. 31, 1996. The overall prevalence of OCD was 1.3% at 40 years of age. Several perinatal factors were independently associated with an increased OCD risk: breech presentation, cesarean section delivery, gestational age of less than 32 weeks, maternal smoking during pregnancy, Apgar scores near the distress level, and both low and high birth weight (defined as 1,500-2,500 g and greater than 4,500 g, respectively).
“These findings contradict the widely held notion that, although mental disorders share genetic risk factors, the contribution of environmental risk factors is largely disorder specific,” with the exception of maternal smoking during pregnancy, the researchers wrote. In addition, the researchers found a dose-response relationship in which the risk for OCD increased with the greater number of perinatal adverse events.
“The findings are important for the understanding of the cause of OCD and will inform future studies of gene by environment interaction and epigenetics,” the researchers said. “If the finding is replication, the association between maternal smoking during pregnancy and OCD may emerge as an interesting disorder-specific risk factor for evaluation in future research,” they added.
Mr. Brander had no financial conflicts to disclose; several coauthors disclosed relationships with companies including Eli Lilly, Shire, and Medice.
Find the full study here: (JAMA Psychiatry. 2016 Oct 5. doi: 10.1001/jamapsychiatry.2016.2095).
Adverse events during the perinatal period were independently associated with an increased risk of obsessive-compulsive disorder at age 40 years, based on data published Oct. 5 from a population-based cohort study of more than 2 million Swedish children.
Perinatal complications, including C-section delivery and preterm birth, have been linked to psychiatric disorders including schizophrenia, autism, and attention-deficit/hyperactivity disorder, but evidence of an impact of obsessive-compulsive disorders has not been well studied, reported Gustaf Brander of the Karolinska Institutet, Stockholm, and his colleagues.
The researchers reviewed data from 2,421,284 live singleton births in Sweden between Jan. 1, 1973, and Dec. 31, 1996. The overall prevalence of OCD was 1.3% at 40 years of age. Several perinatal factors were independently associated with an increased OCD risk: breech presentation, cesarean section delivery, gestational age of less than 32 weeks, maternal smoking during pregnancy, Apgar scores near the distress level, and both low and high birth weight (defined as 1,500-2,500 g and greater than 4,500 g, respectively).
“These findings contradict the widely held notion that, although mental disorders share genetic risk factors, the contribution of environmental risk factors is largely disorder specific,” with the exception of maternal smoking during pregnancy, the researchers wrote. In addition, the researchers found a dose-response relationship in which the risk for OCD increased with the greater number of perinatal adverse events.
“The findings are important for the understanding of the cause of OCD and will inform future studies of gene by environment interaction and epigenetics,” the researchers said. “If the finding is replication, the association between maternal smoking during pregnancy and OCD may emerge as an interesting disorder-specific risk factor for evaluation in future research,” they added.
Mr. Brander had no financial conflicts to disclose; several coauthors disclosed relationships with companies including Eli Lilly, Shire, and Medice.
Find the full study here: (JAMA Psychiatry. 2016 Oct 5. doi: 10.1001/jamapsychiatry.2016.2095).
For HPV-negative women, longer screening intervals are effective
It may be safe to extend cervical cancer screening intervals beyond 5 years, at least for women who are not infected with human papillomavirus.
The rate of cervical cancers was the same among HPV-negative women, whether they had gone through two or three rounds of 5-year exams using both HPV testing and cervical cytology, a large Dutch study has found. This suggests a longer period between screenings wouldn’t significantly increase the risk of letting new cancers go unnoticed, Maaike G Dijkstra, MD, and associates reported (BMJ. 2016;355:i4924. doi: 10.1136/bmj.i4924).
The picture, however, is very different for women with an HPV infection, the researchers noted. These women were 12 times more likely to develop cervical cancer and up to 29 times more likely to have a cervical intraepithelial neoplasia of at least grade 3 (CIN3+), compared with women who were HPV negative.
The findings bring a measure of reassurance to the Dutch population, the researchers wrote. The Netherlands intends to lengthen its cervical cancer screening interval to 10 years for HPV-negative women aged 40 years or older.
“HPV-negative women have a very low risk of CIN3+ in the long term, indicating that extension of the current screening interval in the Netherlands to 10 years seems justifiable,” wrote Dr. Dijkstra of the VU University Medical Centre, Amsterdam, and her colleagues. “For HPV positive, triage negative women, the long term risk of CIN3+ was too high to support an extension of the screening interval beyond 5 years.”
The study assessed the 14-year risks of cervical cancer and CIN3+ in 43,339 women aged 29 years and older. As per national guidelines, all women underwent cervical cancer screening every 5 years, resulting in three rounds. They were randomized to receive HPV and cytology testing or cytology only.
Among HPV-negative women in the double-screening group, the cumulative cervical cancer incidence was 0.03% after round two and 0.09% after round three – not a statistically significant difference.
After round three, cervical cancer incidence among HPV-negative women with negative cytology (double negative) was similar to that among cytology-negative women from the control group after round two.
In the cytology-only group, the rates among negative women were 0.09% after round two of screening and 0.19% after round three.
“This indicated that a negative HPV test provides longer reassurance against cervical cancer than negative cytology,” the researchers noted.
HPV-positive women, however, faced much higher risks, regardless of the screening protocol. Even with negative cytology, they were 12 times more likely to have a cancer by round three than HPV-negative women. The risk of CIN3+ was up to 29 times higher. Even HPV-positive women with negative cytology, negative HPV 16/18 genotyping, and negative repeat cytology faced a 10-fold increased risk of CIN+3, the researchers reported.
Dr. Dijkstra reported having no financial disclosures. Several of the coauthors disclosed financial relationships with various pharmaceutical companies.
[email protected]
On Twitter @Alz_Gal
The ultimate goal of cervical cancer screening is to minimize unnecessary procedures while maximizing identification of preinvasive disease. The recent article by Dr. Dijkstra and her associates provides 14-year follow-up for a national population-based cervical screening randomized trial.
The authors, who focused their analysis on patients older than age 40, describe how HPV results allow for a more targeted intervention triage than cytology alone. The study is impressive in its large patient cohort and extremely low detection rate of cervical cancer among HPV-negative patients in the intervention group. Their main argument stems from identifying an equivalent risk for CIN3+ between patients who were negative for HPV at 10 years and those with negative cytology at 5 years.
In the United States, current guidelines endorse cotesting for patients in this age group, with a negative cotest requiring repeat testing at 5 years. Changes to the screening protocol in the United States are often met with skepticism and slow uptake. This study certainly shows strong data to support HPV testing as the preferred option, but when does the time gap between screenings become too large, particularly for women whose only health care evaluation is through the gynecologist? Patients often think that not needing yearly Pap test equates to no need for routine examinations. We may be missing out on the opportunity to not only grow the patient-physician relationship, but also impact other aspects of the patients’ general health.
This article may not change practice, but it does add considerable weight to the growing literature on primary HPV screening, especially in an older population.
Ritu Salani, MD, is associate professor of gynecologic oncology at Ohio State University in Columbus. Robert T. Neff, MD, is a second-year fellow in gynecologic oncology at the university. They reported having no relevant financial disclosures.
The ultimate goal of cervical cancer screening is to minimize unnecessary procedures while maximizing identification of preinvasive disease. The recent article by Dr. Dijkstra and her associates provides 14-year follow-up for a national population-based cervical screening randomized trial.
The authors, who focused their analysis on patients older than age 40, describe how HPV results allow for a more targeted intervention triage than cytology alone. The study is impressive in its large patient cohort and extremely low detection rate of cervical cancer among HPV-negative patients in the intervention group. Their main argument stems from identifying an equivalent risk for CIN3+ between patients who were negative for HPV at 10 years and those with negative cytology at 5 years.
In the United States, current guidelines endorse cotesting for patients in this age group, with a negative cotest requiring repeat testing at 5 years. Changes to the screening protocol in the United States are often met with skepticism and slow uptake. This study certainly shows strong data to support HPV testing as the preferred option, but when does the time gap between screenings become too large, particularly for women whose only health care evaluation is through the gynecologist? Patients often think that not needing yearly Pap test equates to no need for routine examinations. We may be missing out on the opportunity to not only grow the patient-physician relationship, but also impact other aspects of the patients’ general health.
This article may not change practice, but it does add considerable weight to the growing literature on primary HPV screening, especially in an older population.
Ritu Salani, MD, is associate professor of gynecologic oncology at Ohio State University in Columbus. Robert T. Neff, MD, is a second-year fellow in gynecologic oncology at the university. They reported having no relevant financial disclosures.
The ultimate goal of cervical cancer screening is to minimize unnecessary procedures while maximizing identification of preinvasive disease. The recent article by Dr. Dijkstra and her associates provides 14-year follow-up for a national population-based cervical screening randomized trial.
The authors, who focused their analysis on patients older than age 40, describe how HPV results allow for a more targeted intervention triage than cytology alone. The study is impressive in its large patient cohort and extremely low detection rate of cervical cancer among HPV-negative patients in the intervention group. Their main argument stems from identifying an equivalent risk for CIN3+ between patients who were negative for HPV at 10 years and those with negative cytology at 5 years.
In the United States, current guidelines endorse cotesting for patients in this age group, with a negative cotest requiring repeat testing at 5 years. Changes to the screening protocol in the United States are often met with skepticism and slow uptake. This study certainly shows strong data to support HPV testing as the preferred option, but when does the time gap between screenings become too large, particularly for women whose only health care evaluation is through the gynecologist? Patients often think that not needing yearly Pap test equates to no need for routine examinations. We may be missing out on the opportunity to not only grow the patient-physician relationship, but also impact other aspects of the patients’ general health.
This article may not change practice, but it does add considerable weight to the growing literature on primary HPV screening, especially in an older population.
Ritu Salani, MD, is associate professor of gynecologic oncology at Ohio State University in Columbus. Robert T. Neff, MD, is a second-year fellow in gynecologic oncology at the university. They reported having no relevant financial disclosures.
It may be safe to extend cervical cancer screening intervals beyond 5 years, at least for women who are not infected with human papillomavirus.
The rate of cervical cancers was the same among HPV-negative women, whether they had gone through two or three rounds of 5-year exams using both HPV testing and cervical cytology, a large Dutch study has found. This suggests a longer period between screenings wouldn’t significantly increase the risk of letting new cancers go unnoticed, Maaike G Dijkstra, MD, and associates reported (BMJ. 2016;355:i4924. doi: 10.1136/bmj.i4924).
The picture, however, is very different for women with an HPV infection, the researchers noted. These women were 12 times more likely to develop cervical cancer and up to 29 times more likely to have a cervical intraepithelial neoplasia of at least grade 3 (CIN3+), compared with women who were HPV negative.
The findings bring a measure of reassurance to the Dutch population, the researchers wrote. The Netherlands intends to lengthen its cervical cancer screening interval to 10 years for HPV-negative women aged 40 years or older.
“HPV-negative women have a very low risk of CIN3+ in the long term, indicating that extension of the current screening interval in the Netherlands to 10 years seems justifiable,” wrote Dr. Dijkstra of the VU University Medical Centre, Amsterdam, and her colleagues. “For HPV positive, triage negative women, the long term risk of CIN3+ was too high to support an extension of the screening interval beyond 5 years.”
The study assessed the 14-year risks of cervical cancer and CIN3+ in 43,339 women aged 29 years and older. As per national guidelines, all women underwent cervical cancer screening every 5 years, resulting in three rounds. They were randomized to receive HPV and cytology testing or cytology only.
Among HPV-negative women in the double-screening group, the cumulative cervical cancer incidence was 0.03% after round two and 0.09% after round three – not a statistically significant difference.
After round three, cervical cancer incidence among HPV-negative women with negative cytology (double negative) was similar to that among cytology-negative women from the control group after round two.
In the cytology-only group, the rates among negative women were 0.09% after round two of screening and 0.19% after round three.
“This indicated that a negative HPV test provides longer reassurance against cervical cancer than negative cytology,” the researchers noted.
HPV-positive women, however, faced much higher risks, regardless of the screening protocol. Even with negative cytology, they were 12 times more likely to have a cancer by round three than HPV-negative women. The risk of CIN3+ was up to 29 times higher. Even HPV-positive women with negative cytology, negative HPV 16/18 genotyping, and negative repeat cytology faced a 10-fold increased risk of CIN+3, the researchers reported.
Dr. Dijkstra reported having no financial disclosures. Several of the coauthors disclosed financial relationships with various pharmaceutical companies.
[email protected]
On Twitter @Alz_Gal
It may be safe to extend cervical cancer screening intervals beyond 5 years, at least for women who are not infected with human papillomavirus.
The rate of cervical cancers was the same among HPV-negative women, whether they had gone through two or three rounds of 5-year exams using both HPV testing and cervical cytology, a large Dutch study has found. This suggests a longer period between screenings wouldn’t significantly increase the risk of letting new cancers go unnoticed, Maaike G Dijkstra, MD, and associates reported (BMJ. 2016;355:i4924. doi: 10.1136/bmj.i4924).
The picture, however, is very different for women with an HPV infection, the researchers noted. These women were 12 times more likely to develop cervical cancer and up to 29 times more likely to have a cervical intraepithelial neoplasia of at least grade 3 (CIN3+), compared with women who were HPV negative.
The findings bring a measure of reassurance to the Dutch population, the researchers wrote. The Netherlands intends to lengthen its cervical cancer screening interval to 10 years for HPV-negative women aged 40 years or older.
“HPV-negative women have a very low risk of CIN3+ in the long term, indicating that extension of the current screening interval in the Netherlands to 10 years seems justifiable,” wrote Dr. Dijkstra of the VU University Medical Centre, Amsterdam, and her colleagues. “For HPV positive, triage negative women, the long term risk of CIN3+ was too high to support an extension of the screening interval beyond 5 years.”
The study assessed the 14-year risks of cervical cancer and CIN3+ in 43,339 women aged 29 years and older. As per national guidelines, all women underwent cervical cancer screening every 5 years, resulting in three rounds. They were randomized to receive HPV and cytology testing or cytology only.
Among HPV-negative women in the double-screening group, the cumulative cervical cancer incidence was 0.03% after round two and 0.09% after round three – not a statistically significant difference.
After round three, cervical cancer incidence among HPV-negative women with negative cytology (double negative) was similar to that among cytology-negative women from the control group after round two.
In the cytology-only group, the rates among negative women were 0.09% after round two of screening and 0.19% after round three.
“This indicated that a negative HPV test provides longer reassurance against cervical cancer than negative cytology,” the researchers noted.
HPV-positive women, however, faced much higher risks, regardless of the screening protocol. Even with negative cytology, they were 12 times more likely to have a cancer by round three than HPV-negative women. The risk of CIN3+ was up to 29 times higher. Even HPV-positive women with negative cytology, negative HPV 16/18 genotyping, and negative repeat cytology faced a 10-fold increased risk of CIN+3, the researchers reported.
Dr. Dijkstra reported having no financial disclosures. Several of the coauthors disclosed financial relationships with various pharmaceutical companies.
[email protected]
On Twitter @Alz_Gal
FROM BMJ
Key clinical point:
Major finding: The cumulative cervical cancer incidence was 0.03% after round two and 0.09% after round three – not a statistically significant difference.
Data source: The 14-year study randomized more than 43,000 women to either the double-method screen or just to cervical cytology.
Disclosures: Dr. Dijkstra reported having no financial disclosures. Several of the coauthors disclosed financial relationships with various pharmaceutical companies.
Rivaroxaban linked to more bleeding compared with dabigatran in elderly patients with nonvalvular AF
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
Key clinical point: Rivaroxaban is associated with significantly more intra- and extracranial bleeding than dabigatran in patients aged 75 and older with nonvalvular atrial fibrillation.
Major finding: Rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment.
Data source: A retrospective cohort study of 118,891 patients aged 65 and older who initiated anticoagulation therapy for AF during a 2.5-year period.
Disclosures: This study was conducted by employees or contractors of the Centers for Medicare & Medicaid Services and the Food and Drug Administration. Dr. Graham and his associates reported having no relevant financial disclosures.
COPD patient characteristics predict response to maintenance drug
Azithromycin maintenance therapy may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) and few symptoms, according to an analysis from the COLUMBUS randomized controlled trial. The study, reported on in Family Practice News, also revealed that patients with a high serum eosinophil level… http://www.familypracticenews.com/specialty-focus/pulmonary-sleep-medicine/single-article-page/copd-patient-characteristics-predict-response-to-maintenance-drug/f29efaba9a4874ed9b754fb87b77b663.html.
Azithromycin maintenance therapy may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) and few symptoms, according to an analysis from the COLUMBUS randomized controlled trial. The study, reported on in Family Practice News, also revealed that patients with a high serum eosinophil level… http://www.familypracticenews.com/specialty-focus/pulmonary-sleep-medicine/single-article-page/copd-patient-characteristics-predict-response-to-maintenance-drug/f29efaba9a4874ed9b754fb87b77b663.html.
Azithromycin maintenance therapy may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) and few symptoms, according to an analysis from the COLUMBUS randomized controlled trial. The study, reported on in Family Practice News, also revealed that patients with a high serum eosinophil level… http://www.familypracticenews.com/specialty-focus/pulmonary-sleep-medicine/single-article-page/copd-patient-characteristics-predict-response-to-maintenance-drug/f29efaba9a4874ed9b754fb87b77b663.html.
VIDEO: New oral anticoagulants cut intracranial bleeds in real-world atrial fib patients
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin. But they also had a significantly reduced rate of intracranial hemorrhage, according to Laila Stærk, MD, who reported on the findings at the annual congress of the European Society of Cardiology. The study included 43,299 Danish patients, of which 42% received warfarin, 29% received dabigatran, 16% received apixaban, and 13% received rivaroxaban. More on the results of this study are available in this article and video from Cardiology News: http://www.ecardiologynews.com/specialty-focus/arrhythmias-electrophysiology/single-article-page/video-noacs-cut-intracranial-bleeds-in-real-world-atrial-fib-patients/2c213686c34e2f2e9fb58000ff2cad80.html.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin. But they also had a significantly reduced rate of intracranial hemorrhage, according to Laila Stærk, MD, who reported on the findings at the annual congress of the European Society of Cardiology. The study included 43,299 Danish patients, of which 42% received warfarin, 29% received dabigatran, 16% received apixaban, and 13% received rivaroxaban. More on the results of this study are available in this article and video from Cardiology News: http://www.ecardiologynews.com/specialty-focus/arrhythmias-electrophysiology/single-article-page/video-noacs-cut-intracranial-bleeds-in-real-world-atrial-fib-patients/2c213686c34e2f2e9fb58000ff2cad80.html.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin. But they also had a significantly reduced rate of intracranial hemorrhage, according to Laila Stærk, MD, who reported on the findings at the annual congress of the European Society of Cardiology. The study included 43,299 Danish patients, of which 42% received warfarin, 29% received dabigatran, 16% received apixaban, and 13% received rivaroxaban. More on the results of this study are available in this article and video from Cardiology News: http://www.ecardiologynews.com/specialty-focus/arrhythmias-electrophysiology/single-article-page/video-noacs-cut-intracranial-bleeds-in-real-world-atrial-fib-patients/2c213686c34e2f2e9fb58000ff2cad80.html.
Malignant Transformation of an Aneurysmal Bone Cyst to Fibroblastic Osteosarcoma
Aneurysmal bone cysts (ABC) are expansile, hemorrhagic, non-neoplastic lesions that can be locally destructive1 and that can arise either de novo or secondary to another benign or malignant lesion.2 Although primary and secondary ABCs typically are benign, there are cases of malignant degeneration of primary ABCs, though the transformation arises almost exclusively in the context of prior radiation exposure.3-5 Malignant change without history of irradiation is rare; only 6 such cases have been reported.5-10 In 4 of these cases, the transformation was to osteosarcoma.5,8-10
Here we report on an ABC that degenerated into a fibroblastic osteosarcoma—the fifth such case in the medical literature. In addition to reviewing the earlier cases, we describe the radiologic and histologic underpinnings of this diagnosis and the insight that they provide into the pathogenesis of this rare process. Although the prevailing view is that ABCs are benign, it is important to know these lesions have the potential to undergo malignant transformation, even in the absence of prior radiation exposure. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A healthy and previously asymptomatic 37-year-old man presented with thigh pain after a minor fall onto a couch. Radiographs showed a diaphyseal femoral pathologic fracture adjacent to a small but benign-appearing cystic lesion (Figures 1A, 1B). 
Two years later, the patient had a bicycle accident and, after 2 weeks of significantly increased thigh swelling, presented to the emergency department at the referring institution. Radiographs showed a lytic lesion in the femoral diaphysis that was highly suspicious for malignancy (Figures 3A, 3B). 
The initial biopsy specimens were evaluated at our institution and interpreted as being consistent with an ABC, with negative immunohistochemical staining for MDM2 (Figures 5A, 5B). 
The patient underwent a 3-month course of neoadjuvant chemotherapy with cisplatin and doxorubicin. Interval-staging contrast-enhanced chest, abdomen, and pelvis computed tomography (CT) showed no evidence of metastatic disease. Preoperative MRI showed a significantly larger heterogeneous mass, now with neurovascular involvement, which precluded limb salvage. 
Discussion
Aneurysmal bone cysts are expansile, hemorrhagic, locally destructive lesions that generally develop within the first 3 decades of life. Ever since they were first described by Jaffe and Lichtenstein11 in 1942, the most widely accepted theory of their pathogenesis has been that they begin as a benign reactive vascular process.12 However, more recent molecular studies by Oliveira and colleagues13 and Panoutsakopoulos and colleagues14 have demonstrated a clonal neoplastic basis for primary ABCs related to cytogenetic upregulation of oncogenes USP6 and CDH11 after translocation of 17p13 and 16q22.
Given the clonal nature of these lesions, it is surprising that malignant transformation is so rare. Until now, there have been only 4 reports of an ABC undergoing malignant degeneration to osteosarcoma without prior radiation exposure. 
In this article, we have presented a fifth case of a primary ABC degenerating into an osteosarcoma, which in this instance was the fibroblastic subtype. This diagnosis was strongly supported by radiologic and pathologic evidence. From a radiologic perspective, imaging at initial presentation showed absolutely no suspicious features, and the same was true when follow-up radiographs were obtained, 1 month later. Although 1 month is short for a follow-up, the complete lack of radiographic changes would be highly unusual if in fact there had been a coexisting, undetected lesion as aggressive as the one that ultimately developed. Furthermore, imaging at second presentation, almost 2 years later, showed an extremely rapid evolution of findings over 1 month. Extrapolating back in time, we think this time course indicates the malignancy developed not long before its aggressive features were detected.
Genetic evidence suggests that most conventional high-grade osteosarcomas arise de novo from a mesenchymal precursor driven by multiple genetic aberrations. Less often, low-grade osteosarcomas progress to high-grade osteosarcomas. Amplification of 12q13-15 with resulting overexpression of MDM2 and CDK4 proteins is found in low-grade osteosarcomas and persists in examples that progress to higher-grade forms.15 Not only did review of our patient’s initial biopsy sample reveal no evidence of malignant features or abnormal mitotic activity, but the complete absence of MDM2 suggests not even a low-grade osteosarcoma was present at the time. By contrast, the second incisional biopsy specimen, 2 years later, showed markedly different histology and pronounced expression of MDM2 throughout the specimen. This finding suggests the histologically high-grade osteosarcoma did not arise de novo but rather secondarily from a low-grade osteosarcoma that had arisen from an ABC. Results of the final heterogeneous histology of the very large mass, which contained benign ABC areas indistinguishable from the initial biopsy sample, as well as areas of high-grade osteosarcoma, further support a multistep process of de-differentiation. Together, these findings are compelling evidence of malignant transformation of a primary ABC.
We acknowledge that the initial surgery performed at the outside hospital might have properly included frozen-section analysis of the biopsy material and that sampling error may have occurred during the index procedure—possibilities in the absence of complete lesional resection. In this case, however, the radiographic findings and the dominant histologic immunophenotype from medullary canal bone were both consistent with ABC and not osteosarcoma, lending support to malignant degeneration.
We have presented a fifth case of primary ABC degenerating into an osteosarcoma, now with immunohistochemical evidence supporting traditional radiologic and histologic evidence. Despite the rarity of the diagnosis, this case yields considerable insight into the pathogenetic mechanisms underlying malignant degeneration. Despite the widely held view that ABCs are benign, physicians caring for these patients must be aware that malignant transformation can occur.
Am J Orthop. 2016;45(6):E367-E372. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Donaldson WF. Aneurysmal bone cyst. J Bone Joint Surg Am. 1962;44:25-40.
2. Biesecker JL, Marcove RC, Huvos AG, Miké V. Aneurysmal bone cysts. A clinicopathologic study of 66 cases. Cancer. 1970;26(3):615-625.
3. Aho HJ, Aho AJ, Einola S. Aneurysmal bone cyst, a study of ultrastructure and malignant transformation. Virchows Arch A Pathol Anat Histol. 1982;395(2):169-179.
4. Tillman BP, Dahlin DC, Lipscomb PR, Stewart JR. Aneurysmal bone cyst: an analysis of ninety-five cases. Mayo Clin Proc. 1968;43(7):478-495.
5. Kyriakos M, Hardy D. Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer. 1991;68(8):1770-1780.
6. Mei J, Gao YS, Wang SQ, Cai XS. Malignant transformation of aneurysmal bone cysts: a case report. Chin Med J (Engl). 2009;122(1):110-112.
7. Anract P, de Pinieux G, Jeanrot C, Babinet A, Forest M, Tomeno B. Malignant fibrous histiocytoma at the site of a previously treated aneurysmal bone cyst: a case report. J Bone Joint Surg Am. 2002;84(1):106-111.
8. Hsu CC, Wang JW, Huang CH, Chen WJ. Osteosarcoma at the site of a previously treated aneurysmal bone cyst. A case report. J Bone Joint Surg Am. 2005;87(2):395-398.
9. Wuisman P, Roessner A, Blasius S, Grünert J, Vestering T, Winkelmann W. High malignant surface osteosarcoma arising at the site of a previously treated aneurysmal bone cyst. J Cancer Res Clin Oncol. 1993;119(7):375-378.
10. Brindley GW, Greene JF Jr, Frankel LS. Case reports: malignant transformation of aneurysmal bone cysts. Clin Orthop Relat Res. 2005;(438):282-287.
11. Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: with emphasis on the roentgen picture, the pathologic appearance and the pathogenesis. Arch Surg. 1942;44:1004-1025.
12. Mirra JM. Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA: Lea & Febiger; 1989.
13. Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE. Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006;24(1):e1.
14. Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P, Mertens F, Mandahl N. Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. Genes Chromosomes Cancer. 1999;26(3):265-266.
15. Dujardin F, Binh MB, Bouvier C, et al. MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone. Mod Pathol. 2001;24(5):624-637.
Aneurysmal bone cysts (ABC) are expansile, hemorrhagic, non-neoplastic lesions that can be locally destructive1 and that can arise either de novo or secondary to another benign or malignant lesion.2 Although primary and secondary ABCs typically are benign, there are cases of malignant degeneration of primary ABCs, though the transformation arises almost exclusively in the context of prior radiation exposure.3-5 Malignant change without history of irradiation is rare; only 6 such cases have been reported.5-10 In 4 of these cases, the transformation was to osteosarcoma.5,8-10
Here we report on an ABC that degenerated into a fibroblastic osteosarcoma—the fifth such case in the medical literature. In addition to reviewing the earlier cases, we describe the radiologic and histologic underpinnings of this diagnosis and the insight that they provide into the pathogenesis of this rare process. Although the prevailing view is that ABCs are benign, it is important to know these lesions have the potential to undergo malignant transformation, even in the absence of prior radiation exposure. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A healthy and previously asymptomatic 37-year-old man presented with thigh pain after a minor fall onto a couch. Radiographs showed a diaphyseal femoral pathologic fracture adjacent to a small but benign-appearing cystic lesion (Figures 1A, 1B).
Two years later, the patient had a bicycle accident and, after 2 weeks of significantly increased thigh swelling, presented to the emergency department at the referring institution. Radiographs showed a lytic lesion in the femoral diaphysis that was highly suspicious for malignancy (Figures 3A, 3B).
The initial biopsy specimens were evaluated at our institution and interpreted as being consistent with an ABC, with negative immunohistochemical staining for MDM2 (Figures 5A, 5B).
The patient underwent a 3-month course of neoadjuvant chemotherapy with cisplatin and doxorubicin. Interval-staging contrast-enhanced chest, abdomen, and pelvis computed tomography (CT) showed no evidence of metastatic disease. Preoperative MRI showed a significantly larger heterogeneous mass, now with neurovascular involvement, which precluded limb salvage.
Discussion
Aneurysmal bone cysts are expansile, hemorrhagic, locally destructive lesions that generally develop within the first 3 decades of life. Ever since they were first described by Jaffe and Lichtenstein11 in 1942, the most widely accepted theory of their pathogenesis has been that they begin as a benign reactive vascular process.12 However, more recent molecular studies by Oliveira and colleagues13 and Panoutsakopoulos and colleagues14 have demonstrated a clonal neoplastic basis for primary ABCs related to cytogenetic upregulation of oncogenes USP6 and CDH11 after translocation of 17p13 and 16q22.
Given the clonal nature of these lesions, it is surprising that malignant transformation is so rare. Until now, there have been only 4 reports of an ABC undergoing malignant degeneration to osteosarcoma without prior radiation exposure.
In this article, we have presented a fifth case of a primary ABC degenerating into an osteosarcoma, which in this instance was the fibroblastic subtype. This diagnosis was strongly supported by radiologic and pathologic evidence. From a radiologic perspective, imaging at initial presentation showed absolutely no suspicious features, and the same was true when follow-up radiographs were obtained, 1 month later. Although 1 month is short for a follow-up, the complete lack of radiographic changes would be highly unusual if in fact there had been a coexisting, undetected lesion as aggressive as the one that ultimately developed. Furthermore, imaging at second presentation, almost 2 years later, showed an extremely rapid evolution of findings over 1 month. Extrapolating back in time, we think this time course indicates the malignancy developed not long before its aggressive features were detected.
Genetic evidence suggests that most conventional high-grade osteosarcomas arise de novo from a mesenchymal precursor driven by multiple genetic aberrations. Less often, low-grade osteosarcomas progress to high-grade osteosarcomas. Amplification of 12q13-15 with resulting overexpression of MDM2 and CDK4 proteins is found in low-grade osteosarcomas and persists in examples that progress to higher-grade forms.15 Not only did review of our patient’s initial biopsy sample reveal no evidence of malignant features or abnormal mitotic activity, but the complete absence of MDM2 suggests not even a low-grade osteosarcoma was present at the time. By contrast, the second incisional biopsy specimen, 2 years later, showed markedly different histology and pronounced expression of MDM2 throughout the specimen. This finding suggests the histologically high-grade osteosarcoma did not arise de novo but rather secondarily from a low-grade osteosarcoma that had arisen from an ABC. Results of the final heterogeneous histology of the very large mass, which contained benign ABC areas indistinguishable from the initial biopsy sample, as well as areas of high-grade osteosarcoma, further support a multistep process of de-differentiation. Together, these findings are compelling evidence of malignant transformation of a primary ABC.
We acknowledge that the initial surgery performed at the outside hospital might have properly included frozen-section analysis of the biopsy material and that sampling error may have occurred during the index procedure—possibilities in the absence of complete lesional resection. In this case, however, the radiographic findings and the dominant histologic immunophenotype from medullary canal bone were both consistent with ABC and not osteosarcoma, lending support to malignant degeneration.
We have presented a fifth case of primary ABC degenerating into an osteosarcoma, now with immunohistochemical evidence supporting traditional radiologic and histologic evidence. Despite the rarity of the diagnosis, this case yields considerable insight into the pathogenetic mechanisms underlying malignant degeneration. Despite the widely held view that ABCs are benign, physicians caring for these patients must be aware that malignant transformation can occur.
Am J Orthop. 2016;45(6):E367-E372. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
Aneurysmal bone cysts (ABC) are expansile, hemorrhagic, non-neoplastic lesions that can be locally destructive1 and that can arise either de novo or secondary to another benign or malignant lesion.2 Although primary and secondary ABCs typically are benign, there are cases of malignant degeneration of primary ABCs, though the transformation arises almost exclusively in the context of prior radiation exposure.3-5 Malignant change without history of irradiation is rare; only 6 such cases have been reported.5-10 In 4 of these cases, the transformation was to osteosarcoma.5,8-10
Here we report on an ABC that degenerated into a fibroblastic osteosarcoma—the fifth such case in the medical literature. In addition to reviewing the earlier cases, we describe the radiologic and histologic underpinnings of this diagnosis and the insight that they provide into the pathogenesis of this rare process. Although the prevailing view is that ABCs are benign, it is important to know these lesions have the potential to undergo malignant transformation, even in the absence of prior radiation exposure. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A healthy and previously asymptomatic 37-year-old man presented with thigh pain after a minor fall onto a couch. Radiographs showed a diaphyseal femoral pathologic fracture adjacent to a small but benign-appearing cystic lesion (Figures 1A, 1B).
Two years later, the patient had a bicycle accident and, after 2 weeks of significantly increased thigh swelling, presented to the emergency department at the referring institution. Radiographs showed a lytic lesion in the femoral diaphysis that was highly suspicious for malignancy (Figures 3A, 3B).
The initial biopsy specimens were evaluated at our institution and interpreted as being consistent with an ABC, with negative immunohistochemical staining for MDM2 (Figures 5A, 5B).
The patient underwent a 3-month course of neoadjuvant chemotherapy with cisplatin and doxorubicin. Interval-staging contrast-enhanced chest, abdomen, and pelvis computed tomography (CT) showed no evidence of metastatic disease. Preoperative MRI showed a significantly larger heterogeneous mass, now with neurovascular involvement, which precluded limb salvage.
Discussion
Aneurysmal bone cysts are expansile, hemorrhagic, locally destructive lesions that generally develop within the first 3 decades of life. Ever since they were first described by Jaffe and Lichtenstein11 in 1942, the most widely accepted theory of their pathogenesis has been that they begin as a benign reactive vascular process.12 However, more recent molecular studies by Oliveira and colleagues13 and Panoutsakopoulos and colleagues14 have demonstrated a clonal neoplastic basis for primary ABCs related to cytogenetic upregulation of oncogenes USP6 and CDH11 after translocation of 17p13 and 16q22.
Given the clonal nature of these lesions, it is surprising that malignant transformation is so rare. Until now, there have been only 4 reports of an ABC undergoing malignant degeneration to osteosarcoma without prior radiation exposure.
In this article, we have presented a fifth case of a primary ABC degenerating into an osteosarcoma, which in this instance was the fibroblastic subtype. This diagnosis was strongly supported by radiologic and pathologic evidence. From a radiologic perspective, imaging at initial presentation showed absolutely no suspicious features, and the same was true when follow-up radiographs were obtained, 1 month later. Although 1 month is short for a follow-up, the complete lack of radiographic changes would be highly unusual if in fact there had been a coexisting, undetected lesion as aggressive as the one that ultimately developed. Furthermore, imaging at second presentation, almost 2 years later, showed an extremely rapid evolution of findings over 1 month. Extrapolating back in time, we think this time course indicates the malignancy developed not long before its aggressive features were detected.
Genetic evidence suggests that most conventional high-grade osteosarcomas arise de novo from a mesenchymal precursor driven by multiple genetic aberrations. Less often, low-grade osteosarcomas progress to high-grade osteosarcomas. Amplification of 12q13-15 with resulting overexpression of MDM2 and CDK4 proteins is found in low-grade osteosarcomas and persists in examples that progress to higher-grade forms.15 Not only did review of our patient’s initial biopsy sample reveal no evidence of malignant features or abnormal mitotic activity, but the complete absence of MDM2 suggests not even a low-grade osteosarcoma was present at the time. By contrast, the second incisional biopsy specimen, 2 years later, showed markedly different histology and pronounced expression of MDM2 throughout the specimen. This finding suggests the histologically high-grade osteosarcoma did not arise de novo but rather secondarily from a low-grade osteosarcoma that had arisen from an ABC. Results of the final heterogeneous histology of the very large mass, which contained benign ABC areas indistinguishable from the initial biopsy sample, as well as areas of high-grade osteosarcoma, further support a multistep process of de-differentiation. Together, these findings are compelling evidence of malignant transformation of a primary ABC.
We acknowledge that the initial surgery performed at the outside hospital might have properly included frozen-section analysis of the biopsy material and that sampling error may have occurred during the index procedure—possibilities in the absence of complete lesional resection. In this case, however, the radiographic findings and the dominant histologic immunophenotype from medullary canal bone were both consistent with ABC and not osteosarcoma, lending support to malignant degeneration.
We have presented a fifth case of primary ABC degenerating into an osteosarcoma, now with immunohistochemical evidence supporting traditional radiologic and histologic evidence. Despite the rarity of the diagnosis, this case yields considerable insight into the pathogenetic mechanisms underlying malignant degeneration. Despite the widely held view that ABCs are benign, physicians caring for these patients must be aware that malignant transformation can occur.
Am J Orthop. 2016;45(6):E367-E372. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Donaldson WF. Aneurysmal bone cyst. J Bone Joint Surg Am. 1962;44:25-40.
2. Biesecker JL, Marcove RC, Huvos AG, Miké V. Aneurysmal bone cysts. A clinicopathologic study of 66 cases. Cancer. 1970;26(3):615-625.
3. Aho HJ, Aho AJ, Einola S. Aneurysmal bone cyst, a study of ultrastructure and malignant transformation. Virchows Arch A Pathol Anat Histol. 1982;395(2):169-179.
4. Tillman BP, Dahlin DC, Lipscomb PR, Stewart JR. Aneurysmal bone cyst: an analysis of ninety-five cases. Mayo Clin Proc. 1968;43(7):478-495.
5. Kyriakos M, Hardy D. Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer. 1991;68(8):1770-1780.
6. Mei J, Gao YS, Wang SQ, Cai XS. Malignant transformation of aneurysmal bone cysts: a case report. Chin Med J (Engl). 2009;122(1):110-112.
7. Anract P, de Pinieux G, Jeanrot C, Babinet A, Forest M, Tomeno B. Malignant fibrous histiocytoma at the site of a previously treated aneurysmal bone cyst: a case report. J Bone Joint Surg Am. 2002;84(1):106-111.
8. Hsu CC, Wang JW, Huang CH, Chen WJ. Osteosarcoma at the site of a previously treated aneurysmal bone cyst. A case report. J Bone Joint Surg Am. 2005;87(2):395-398.
9. Wuisman P, Roessner A, Blasius S, Grünert J, Vestering T, Winkelmann W. High malignant surface osteosarcoma arising at the site of a previously treated aneurysmal bone cyst. J Cancer Res Clin Oncol. 1993;119(7):375-378.
10. Brindley GW, Greene JF Jr, Frankel LS. Case reports: malignant transformation of aneurysmal bone cysts. Clin Orthop Relat Res. 2005;(438):282-287.
11. Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: with emphasis on the roentgen picture, the pathologic appearance and the pathogenesis. Arch Surg. 1942;44:1004-1025.
12. Mirra JM. Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA: Lea & Febiger; 1989.
13. Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE. Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006;24(1):e1.
14. Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P, Mertens F, Mandahl N. Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. Genes Chromosomes Cancer. 1999;26(3):265-266.
15. Dujardin F, Binh MB, Bouvier C, et al. MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone. Mod Pathol. 2001;24(5):624-637.
1. Donaldson WF. Aneurysmal bone cyst. J Bone Joint Surg Am. 1962;44:25-40.
2. Biesecker JL, Marcove RC, Huvos AG, Miké V. Aneurysmal bone cysts. A clinicopathologic study of 66 cases. Cancer. 1970;26(3):615-625.
3. Aho HJ, Aho AJ, Einola S. Aneurysmal bone cyst, a study of ultrastructure and malignant transformation. Virchows Arch A Pathol Anat Histol. 1982;395(2):169-179.
4. Tillman BP, Dahlin DC, Lipscomb PR, Stewart JR. Aneurysmal bone cyst: an analysis of ninety-five cases. Mayo Clin Proc. 1968;43(7):478-495.
5. Kyriakos M, Hardy D. Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer. 1991;68(8):1770-1780.
6. Mei J, Gao YS, Wang SQ, Cai XS. Malignant transformation of aneurysmal bone cysts: a case report. Chin Med J (Engl). 2009;122(1):110-112.
7. Anract P, de Pinieux G, Jeanrot C, Babinet A, Forest M, Tomeno B. Malignant fibrous histiocytoma at the site of a previously treated aneurysmal bone cyst: a case report. J Bone Joint Surg Am. 2002;84(1):106-111.
8. Hsu CC, Wang JW, Huang CH, Chen WJ. Osteosarcoma at the site of a previously treated aneurysmal bone cyst. A case report. J Bone Joint Surg Am. 2005;87(2):395-398.
9. Wuisman P, Roessner A, Blasius S, Grünert J, Vestering T, Winkelmann W. High malignant surface osteosarcoma arising at the site of a previously treated aneurysmal bone cyst. J Cancer Res Clin Oncol. 1993;119(7):375-378.
10. Brindley GW, Greene JF Jr, Frankel LS. Case reports: malignant transformation of aneurysmal bone cysts. Clin Orthop Relat Res. 2005;(438):282-287.
11. Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: with emphasis on the roentgen picture, the pathologic appearance and the pathogenesis. Arch Surg. 1942;44:1004-1025.
12. Mirra JM. Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA: Lea & Febiger; 1989.
13. Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE. Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006;24(1):e1.
14. Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P, Mertens F, Mandahl N. Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. Genes Chromosomes Cancer. 1999;26(3):265-266.
15. Dujardin F, Binh MB, Bouvier C, et al. MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone. Mod Pathol. 2001;24(5):624-637.
Cerebral protection in TAVI reduces ischemic brain lesions
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
These findings are compelling and encouraging, even though we don’t yet know whether the reduction in the number and volume of ischemic brain lesions translates into clinical benefit.
The results also confirm what previous research has suggested: that emboli to the brain are extremely common and do cause small infarctions detectable on MRI. In this trial, virtually every patient demonstrated such acute lesions, though the vast majority were quite small.
Steven R. Messe, MD, is in the department of neurology at the Hospital of the University of Pennsylvania, Philadelphia. Michael J. Mack, MD, is in the department of cardiac surgery at The Heart Hospital Baylor Plano in Plano, Tex. Dr. Messe reported ties to GlaxoSmithKline; Dr. Mack reported having no relevant financial disclosures. Dr. Messe and Dr. Mack made these remarks in an editorial accompanying Dr. Haussig’s report (JAMA 2016;316[6]:587-8).
These findings are compelling and encouraging, even though we don’t yet know whether the reduction in the number and volume of ischemic brain lesions translates into clinical benefit.
The results also confirm what previous research has suggested: that emboli to the brain are extremely common and do cause small infarctions detectable on MRI. In this trial, virtually every patient demonstrated such acute lesions, though the vast majority were quite small.
Steven R. Messe, MD, is in the department of neurology at the Hospital of the University of Pennsylvania, Philadelphia. Michael J. Mack, MD, is in the department of cardiac surgery at The Heart Hospital Baylor Plano in Plano, Tex. Dr. Messe reported ties to GlaxoSmithKline; Dr. Mack reported having no relevant financial disclosures. Dr. Messe and Dr. Mack made these remarks in an editorial accompanying Dr. Haussig’s report (JAMA 2016;316[6]:587-8).
These findings are compelling and encouraging, even though we don’t yet know whether the reduction in the number and volume of ischemic brain lesions translates into clinical benefit.
The results also confirm what previous research has suggested: that emboli to the brain are extremely common and do cause small infarctions detectable on MRI. In this trial, virtually every patient demonstrated such acute lesions, though the vast majority were quite small.
Steven R. Messe, MD, is in the department of neurology at the Hospital of the University of Pennsylvania, Philadelphia. Michael J. Mack, MD, is in the department of cardiac surgery at The Heart Hospital Baylor Plano in Plano, Tex. Dr. Messe reported ties to GlaxoSmithKline; Dr. Mack reported having no relevant financial disclosures. Dr. Messe and Dr. Mack made these remarks in an editorial accompanying Dr. Haussig’s report (JAMA 2016;316[6]:587-8).
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Key clinical point: In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions.
Major finding: At 2 days, the number of new brain lesions was markedly lower in the filter group than in the control group (8 vs. 16), as was the lesion volume (466 mm vs. 800 mm).
Data source: A prospective single-center randomized clinical trial involving 100 patients undergoing TAVI for severe aortic stenosis.
Disclosures: This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.