SAN FRANCISCO – Congressional funding of the National Institutes of Health’s HEAL Initiative represents an unprecedented golden opportunity for research funding on headache and other pain conditions, according to Michael L. Oshinsky, PhD, a neurobiologist who serves as program director for pain and migraine at the National Institute of Neurological Disorders and Stroke (NINDS).

“This is a once-in-a-lifetime opportunity for physician researchers and basic science researchers to identify projects and request funding from NIH. This is an amount of money that doesn’t come along very often. It’s really a once in a lifetime situation, and I implore you to take advantage of this tremendous opportunity,” he urged attendees at the annual meeting of the American Headache Society.

Congress gave the NIH $500 million for the HEAL (Helping to End Addiction Long-term) Initiative to be spent over the course of fiscal years 2018 and 2019. The money is to be split equally on the initiative’s two components: opioid use disorder and pain management.

“We’re going to spend $250 million on pain, be sure of it,” Dr. Oshinsky promised.

Pain management issues cut across all 27 NIH institutes and centers. However, the biggest chunk of the money goes to NINDS, which leads the NIH Pain Consortium, charged with enhancing pain research and promoting collaboration across NIH.

Within NINDS, funding for migraine research has been formally designated as an HPP, or high program priority, according to Dr. Oshinsky.

“Headache research gets funded. It really does. I want to dispel the myth that there isn’t an interest in headache research or migraine research at NIH. Currently, at NINDS, we have more than 60 funded projects that specifically address scientific questions about migraine and headache. That’s more than any other government in the world,” he said.

And it’s not all basic science research related to headache that NINDS is interested in fostering, either. The institute is eager to fund large clinical trials, pediatric headache research, studies of device therapies, and a wealth of other projects.

Among the HEAL initiatives that have already been approved is a project aimed at identifying and validating new pain targets. Another is focused upon finding risk factors with clinically meaningful predictive value for transition from acute to chronic pain, be they biomarkers, imaging findings, or genetic characteristics. Yet another program is an NIH-industry collaboration that aims to identify new treatments for pain that are nonaddictive, nonrewarding, nonsedating, and safe across age groups; candidate biologics, small molecules, devices, and natural products will be screened in vitro and in animal models, with the successful ones moving on to clinical trials.

Funding opportunity announcements are imminent for creation of a planned NIH clinical trials network for pain research, which will conduct phase 2 trials in specialized pain centers. The focus will be on well-characterized pain conditions with high unmet medical need, including headache as well as orofacial, pelvic, gastrointestinal, and cancer pain.

Dr. Oshinsky encouraged academicians to have their fellows apply for the NIH early career development awards known as K awards.

“They are much easier to get than R01 awards and they provide a tremendous opportunity for jump-starting the career of new scientists in the headache field. Have them reach out to me. I can help them through the process, help them develop their project, and get them funded with a K award. And the transition from a K award to an R01 is a much smoother transition,” he said.

Research funding proposals should use the NINDS Common Data Elements for headache, recently updated by more than 40 experts in headache medicine and research.

Dr. Oshinsky said most of the new pain management programs will be funded in fiscal year 2019. These novel programs have to be approved by oversight committees, and that takes time. The reason that the bulk of HEAL Initiative funding in fiscal year 2018 is going for opioid use disorder is that much of that money is being spent on expansion of existing programs, which can quickly be ramped up without the same degree of oversight required for new programs.

[email protected]

SAN FRANCISCO – Congressional funding of the National Institutes of Health’s HEAL Initiative represents an unprecedented golden opportunity for research funding on headache and other pain conditions, according to Michael L. Oshinsky, PhD, a neurobiologist who serves as program director for pain and migraine at the National Institute of Neurological Disorders and Stroke (NINDS).

“This is a once-in-a-lifetime opportunity for physician researchers and basic science researchers to identify projects and request funding from NIH. This is an amount of money that doesn’t come along very often. It’s really a once in a lifetime situation, and I implore you to take advantage of this tremendous opportunity,” he urged attendees at the annual meeting of the American Headache Society.

Congress gave the NIH $500 million for the HEAL (Helping to End Addiction Long-term) Initiative to be spent over the course of fiscal years 2018 and 2019. The money is to be split equally on the initiative’s two components: opioid use disorder and pain management.

“We’re going to spend $250 million on pain, be sure of it,” Dr. Oshinsky promised.

Pain management issues cut across all 27 NIH institutes and centers. However, the biggest chunk of the money goes to NINDS, which leads the NIH Pain Consortium, charged with enhancing pain research and promoting collaboration across NIH.

Within NINDS, funding for migraine research has been formally designated as an HPP, or high program priority, according to Dr. Oshinsky.

“Headache research gets funded. It really does. I want to dispel the myth that there isn’t an interest in headache research or migraine research at NIH. Currently, at NINDS, we have more than 60 funded projects that specifically address scientific questions about migraine and headache. That’s more than any other government in the world,” he said.

And it’s not all basic science research related to headache that NINDS is interested in fostering, either. The institute is eager to fund large clinical trials, pediatric headache research, studies of device therapies, and a wealth of other projects.

Among the HEAL initiatives that have already been approved is a project aimed at identifying and validating new pain targets. Another is focused upon finding risk factors with clinically meaningful predictive value for transition from acute to chronic pain, be they biomarkers, imaging findings, or genetic characteristics. Yet another program is an NIH-industry collaboration that aims to identify new treatments for pain that are nonaddictive, nonrewarding, nonsedating, and safe across age groups; candidate biologics, small molecules, devices, and natural products will be screened in vitro and in animal models, with the successful ones moving on to clinical trials.

Funding opportunity announcements are imminent for creation of a planned NIH clinical trials network for pain research, which will conduct phase 2 trials in specialized pain centers. The focus will be on well-characterized pain conditions with high unmet medical need, including headache as well as orofacial, pelvic, gastrointestinal, and cancer pain.

Dr. Oshinsky encouraged academicians to have their fellows apply for the NIH early career development awards known as K awards.

“They are much easier to get than R01 awards and they provide a tremendous opportunity for jump-starting the career of new scientists in the headache field. Have them reach out to me. I can help them through the process, help them develop their project, and get them funded with a K award. And the transition from a K award to an R01 is a much smoother transition,” he said.

Research funding proposals should use the NINDS Common Data Elements for headache, recently updated by more than 40 experts in headache medicine and research.

Dr. Oshinsky said most of the new pain management programs will be funded in fiscal year 2019. These novel programs have to be approved by oversight committees, and that takes time. The reason that the bulk of HEAL Initiative funding in fiscal year 2018 is going for opioid use disorder is that much of that money is being spent on expansion of existing programs, which can quickly be ramped up without the same degree of oversight required for new programs.

[email protected]

SAN FRANCISCO – Congressional funding of the National Institutes of Health’s HEAL Initiative represents an unprecedented golden opportunity for research funding on headache and other pain conditions, according to Michael L. Oshinsky, PhD, a neurobiologist who serves as program director for pain and migraine at the National Institute of Neurological Disorders and Stroke (NINDS).

“This is a once-in-a-lifetime opportunity for physician researchers and basic science researchers to identify projects and request funding from NIH. This is an amount of money that doesn’t come along very often. It’s really a once in a lifetime situation, and I implore you to take advantage of this tremendous opportunity,” he urged attendees at the annual meeting of the American Headache Society.

Congress gave the NIH $500 million for the HEAL (Helping to End Addiction Long-term) Initiative to be spent over the course of fiscal years 2018 and 2019. The money is to be split equally on the initiative’s two components: opioid use disorder and pain management.

“We’re going to spend $250 million on pain, be sure of it,” Dr. Oshinsky promised.

Pain management issues cut across all 27 NIH institutes and centers. However, the biggest chunk of the money goes to NINDS, which leads the NIH Pain Consortium, charged with enhancing pain research and promoting collaboration across NIH.

Within NINDS, funding for migraine research has been formally designated as an HPP, or high program priority, according to Dr. Oshinsky.

“Headache research gets funded. It really does. I want to dispel the myth that there isn’t an interest in headache research or migraine research at NIH. Currently, at NINDS, we have more than 60 funded projects that specifically address scientific questions about migraine and headache. That’s more than any other government in the world,” he said.

And it’s not all basic science research related to headache that NINDS is interested in fostering, either. The institute is eager to fund large clinical trials, pediatric headache research, studies of device therapies, and a wealth of other projects.

Among the HEAL initiatives that have already been approved is a project aimed at identifying and validating new pain targets. Another is focused upon finding risk factors with clinically meaningful predictive value for transition from acute to chronic pain, be they biomarkers, imaging findings, or genetic characteristics. Yet another program is an NIH-industry collaboration that aims to identify new treatments for pain that are nonaddictive, nonrewarding, nonsedating, and safe across age groups; candidate biologics, small molecules, devices, and natural products will be screened in vitro and in animal models, with the successful ones moving on to clinical trials.

Funding opportunity announcements are imminent for creation of a planned NIH clinical trials network for pain research, which will conduct phase 2 trials in specialized pain centers. The focus will be on well-characterized pain conditions with high unmet medical need, including headache as well as orofacial, pelvic, gastrointestinal, and cancer pain.

Dr. Oshinsky encouraged academicians to have their fellows apply for the NIH early career development awards known as K awards.

“They are much easier to get than R01 awards and they provide a tremendous opportunity for jump-starting the career of new scientists in the headache field. Have them reach out to me. I can help them through the process, help them develop their project, and get them funded with a K award. And the transition from a K award to an R01 is a much smoother transition,” he said.

Research funding proposals should use the NINDS Common Data Elements for headache, recently updated by more than 40 experts in headache medicine and research.

Dr. Oshinsky said most of the new pain management programs will be funded in fiscal year 2019. These novel programs have to be approved by oversight committees, and that takes time. The reason that the bulk of HEAL Initiative funding in fiscal year 2018 is going for opioid use disorder is that much of that money is being spent on expansion of existing programs, which can quickly be ramped up without the same degree of oversight required for new programs.

[email protected]

If you are a current AGA trainee, medical resident, or student member, please renew your membership today to ensure the continuation of your career-enhancing benefits for the upcoming membership year. Prepare for your next chapter with the latest news and breakthroughs in the field, as well as access to educational programs, events and much more.

While renewing, please update your member profile at My AGA for news and resources tailored to your professional interests. The deadline to renew is Aug. 31, 2018.

If you have any questions, please contact AGA Member Relations at [email protected] or 301-941-2651.

If you are a current AGA trainee, medical resident, or student member, please renew your membership today to ensure the continuation of your career-enhancing benefits for the upcoming membership year. Prepare for your next chapter with the latest news and breakthroughs in the field, as well as access to educational programs, events and much more.

While renewing, please update your member profile at My AGA for news and resources tailored to your professional interests. The deadline to renew is Aug. 31, 2018.

If you have any questions, please contact AGA Member Relations at [email protected] or 301-941-2651.

If you are a current AGA trainee, medical resident, or student member, please renew your membership today to ensure the continuation of your career-enhancing benefits for the upcoming membership year. Prepare for your next chapter with the latest news and breakthroughs in the field, as well as access to educational programs, events and much more.

While renewing, please update your member profile at My AGA for news and resources tailored to your professional interests. The deadline to renew is Aug. 31, 2018.

If you have any questions, please contact AGA Member Relations at [email protected] or 301-941-2651.

The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.

More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.

The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.

The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.

Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.

[email protected]

The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.

More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.

The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.

The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.

Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.

[email protected]

The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.

More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.

The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.

The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.

Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.

[email protected]

Successful careers don’t just happen. They are made by individuals who take charge and build their own success. The alternative is burnout.

“Part of burnout is feeling overburdened, overworked, and out of control,” said Barbara Jung, MD, AGAF, professor and chief of gastroenterology and hepatology at the University of Illinois at Chicago, during Strategies for a Successful Career: Wellness, Empowerment, Leadership and Resilience at Digestive Disease Week^® (DDW) 2018. “If somebody is staying until 9 or 10 o’clock [at night] to finish notes, I have a discussion with them. It is good to be done at 5 p.m. and go home. It is all about setting your own priorities and not letting the job take over your life.”

Associations have a role to play, too. The ASGE Technology Committee reported in 2010 that up to 89% of GIs suffer musculoskeletal injuries from manipulating scopes. Colonoscopist’s thumb (left thumb tendonitis) and metacarpophalangeal joint strain were the most common injuries.

“Risk factors are part of our work,” said Mehnaz Shafi, MD, AGAF, professor of gastroenterology, hepatology and nutrition at the University of Texas MD Anderson Cancer Center, Houston. “Pinching, pushing, pulling, and awkward positions are part of what we do. This is an injury with consequences.”

Dr. Shafi chairs the AGA Task Force on Ergonomics. The group has recommended changes to endoscopic work stations that minimize injury. The most important changes include mounting monitors on flexible stands to accommodate GIs of all heights, adding straps to the control head to allow the fingers to relax, providing ergonomic training to all GIs and using patient beds that can be raised and lowered to accommodate both tall and short GIs.

“Shaping your career is one of the key principles in preventing burnout,” said Arthur DeCross, MD, AGAF, professor of medicine, gastroenterology and hepatology at the University of Rochester Medical Center, N.Y. “We know that more than half of gastroenterologists self-identify as being burned out. And one of the major contributors to burnout is lack of control over your work environment, your career, your colleagues. Taking control of your career can make a difference.”

Taking control can be particularly important for women. An AGA burnout survey in 2015 found that 51% of male GIs reported burnout versus 62% of female GIs.

One reason is women’s tendency to negotiate poorly on their own behalf, said Marie-Pier Tétreault, PhD, assistant professor of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine, Chicago.

“It’s a matter of attitude,” she explained. “Men tend to believe they can and should make life happen. Women tend to believe that what you see is what you get. Even when women do negotiate, they tend to ask for 15%-30% less than their male colleagues. If you don’t ask, you won’t get.”

Simply taking the lead in negotiations can improve the outcome, she continued. Network with colleagues and mentors to find the appropriate ranges for salaries, benefits, and perks such as parking, spousal job opportunities, facilities and space, teaching expectations, administrative support, and more.

Successful careers don’t just happen. They are made by individuals who take charge and build their own success. The alternative is burnout.

“Part of burnout is feeling overburdened, overworked, and out of control,” said Barbara Jung, MD, AGAF, professor and chief of gastroenterology and hepatology at the University of Illinois at Chicago, during Strategies for a Successful Career: Wellness, Empowerment, Leadership and Resilience at Digestive Disease Week^® (DDW) 2018. “If somebody is staying until 9 or 10 o’clock [at night] to finish notes, I have a discussion with them. It is good to be done at 5 p.m. and go home. It is all about setting your own priorities and not letting the job take over your life.”

Associations have a role to play, too. The ASGE Technology Committee reported in 2010 that up to 89% of GIs suffer musculoskeletal injuries from manipulating scopes. Colonoscopist’s thumb (left thumb tendonitis) and metacarpophalangeal joint strain were the most common injuries.

“Risk factors are part of our work,” said Mehnaz Shafi, MD, AGAF, professor of gastroenterology, hepatology and nutrition at the University of Texas MD Anderson Cancer Center, Houston. “Pinching, pushing, pulling, and awkward positions are part of what we do. This is an injury with consequences.”

Dr. Shafi chairs the AGA Task Force on Ergonomics. The group has recommended changes to endoscopic work stations that minimize injury. The most important changes include mounting monitors on flexible stands to accommodate GIs of all heights, adding straps to the control head to allow the fingers to relax, providing ergonomic training to all GIs and using patient beds that can be raised and lowered to accommodate both tall and short GIs.

“Shaping your career is one of the key principles in preventing burnout,” said Arthur DeCross, MD, AGAF, professor of medicine, gastroenterology and hepatology at the University of Rochester Medical Center, N.Y. “We know that more than half of gastroenterologists self-identify as being burned out. And one of the major contributors to burnout is lack of control over your work environment, your career, your colleagues. Taking control of your career can make a difference.”

Taking control can be particularly important for women. An AGA burnout survey in 2015 found that 51% of male GIs reported burnout versus 62% of female GIs.

One reason is women’s tendency to negotiate poorly on their own behalf, said Marie-Pier Tétreault, PhD, assistant professor of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine, Chicago.

“It’s a matter of attitude,” she explained. “Men tend to believe they can and should make life happen. Women tend to believe that what you see is what you get. Even when women do negotiate, they tend to ask for 15%-30% less than their male colleagues. If you don’t ask, you won’t get.”

Simply taking the lead in negotiations can improve the outcome, she continued. Network with colleagues and mentors to find the appropriate ranges for salaries, benefits, and perks such as parking, spousal job opportunities, facilities and space, teaching expectations, administrative support, and more.

Successful careers don’t just happen. They are made by individuals who take charge and build their own success. The alternative is burnout.

“Part of burnout is feeling overburdened, overworked, and out of control,” said Barbara Jung, MD, AGAF, professor and chief of gastroenterology and hepatology at the University of Illinois at Chicago, during Strategies for a Successful Career: Wellness, Empowerment, Leadership and Resilience at Digestive Disease Week^® (DDW) 2018. “If somebody is staying until 9 or 10 o’clock [at night] to finish notes, I have a discussion with them. It is good to be done at 5 p.m. and go home. It is all about setting your own priorities and not letting the job take over your life.”

Associations have a role to play, too. The ASGE Technology Committee reported in 2010 that up to 89% of GIs suffer musculoskeletal injuries from manipulating scopes. Colonoscopist’s thumb (left thumb tendonitis) and metacarpophalangeal joint strain were the most common injuries.

“Risk factors are part of our work,” said Mehnaz Shafi, MD, AGAF, professor of gastroenterology, hepatology and nutrition at the University of Texas MD Anderson Cancer Center, Houston. “Pinching, pushing, pulling, and awkward positions are part of what we do. This is an injury with consequences.”

Dr. Shafi chairs the AGA Task Force on Ergonomics. The group has recommended changes to endoscopic work stations that minimize injury. The most important changes include mounting monitors on flexible stands to accommodate GIs of all heights, adding straps to the control head to allow the fingers to relax, providing ergonomic training to all GIs and using patient beds that can be raised and lowered to accommodate both tall and short GIs.

“Shaping your career is one of the key principles in preventing burnout,” said Arthur DeCross, MD, AGAF, professor of medicine, gastroenterology and hepatology at the University of Rochester Medical Center, N.Y. “We know that more than half of gastroenterologists self-identify as being burned out. And one of the major contributors to burnout is lack of control over your work environment, your career, your colleagues. Taking control of your career can make a difference.”

Taking control can be particularly important for women. An AGA burnout survey in 2015 found that 51% of male GIs reported burnout versus 62% of female GIs.

One reason is women’s tendency to negotiate poorly on their own behalf, said Marie-Pier Tétreault, PhD, assistant professor of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine, Chicago.

“It’s a matter of attitude,” she explained. “Men tend to believe they can and should make life happen. Women tend to believe that what you see is what you get. Even when women do negotiate, they tend to ask for 15%-30% less than their male colleagues. If you don’t ask, you won’t get.”

Simply taking the lead in negotiations can improve the outcome, she continued. Network with colleagues and mentors to find the appropriate ranges for salaries, benefits, and perks such as parking, spousal job opportunities, facilities and space, teaching expectations, administrative support, and more.

The Essure permanent birth control device will no longer be sold or distributed after Dec. 31, 2018, in the United States.

Bayer, the manufacturer of Essure, notified the Food and Drug Administration of its decision to halt U.S. sales of the device, Commissioner Scott Gottlieb, MD, announced July 20 in a press release. Dr. Gottlieb added that the agency would continue its commitment to postmarketing review of Essure. “We expect Bayer to meet its postmarket obligations concerning this device.”

Since its approval, Essure is estimated to have been used by more than 750,000 patients worldwide, the FDA release stated. The device has been associated with serious risks, including persistent pain, perforation of the uterus and fallopian tubes, and migration of the coils into the pelvis or abdomen.

“In April, when the FDA became aware that many patients were not being adequately counseled, we required a restriction, which limits the sale and distribution of the device to only health care providers and facilities that provide information to patients about the risks and benefits of this device and gives patients the opportunity to sign an acknowledgment that they fully understood these potential risks before having the device implanted. Since the FDA ordered Bayer to conduct the postmarket study and then to add a boxed warning and a Patient Decision Checklist to the labeling, there has been an approximate 70% decline in sales of Essure in the United States,” Dr. Gottlieb said in the FDA press release. The company stated its decision to halt sales and distribution of the device was because of commercial reasons.

“Numerous adverse events ... were reported to the FDA, including a significant collection of recent reports that have mentioned issues involving surgery to remove the device. We’re continuing our evaluation of these reports to better understand reasons for the device removal. The agency is committed to continuing to provide updates on our evaluation of this data as the information is collected and we develop new findings about the device.”

In September 2015, the FDA convened an expert panel to examine and follow up on complaints from Essure users that included abdominal pain, abnormal uterine bleeding, and device migration. In February 2016, the FDA ordered Bayer to conduct a postmarket (522) study to better evaluate the safety profile of the device when used in the real world. The following October, the agency issued the final guidance, “Labeling for Permanent Hysteroscopically Placed Tubal Implants Intended for Sterilization.” Soon thereafter, the FDA approved updated labeling for Essure that added a boxed warning and a Patient Decision Checklist.

In March 2018, the FDA reported a rise in new medical device reports submitted to the agency’s public database in 2017, with more than 90% of the reports involving potential device removal. The April restriction of sales and distribution was in response to concerns that not every patient was receiving adequate risk information.

“I want to stress that, even when Essure is no longer sold, the FDA will remain vigilant in protecting patients who’ve already had this device implanted. We’ll continue to monitor adverse events reported to our database, as well as other data sources. And we’ll communicate publicly on any new findings or concerns. The restriction on sale and distribution will remain in place. Regarding the postmarket 522 study, Bayer will continue to enroll new participants. Each study participant will be followed for a total of 3 years, and the company will continue to submit reports to the FDA on the study’s progress and results. Since Bayer will not be able to meet its expected enrollment numbers for this study that relied on enrolling patients who were newly implanted with Essure, we’ll be working with the company to best determine how to move forward to answer the critical questions we posed concerning certain patient complications that may be experienced by patients who have Essure,” Dr. Gottlieb stated.

He added that women who are using Essure successfully to prevent pregnancy should continue to do so, as “device removal has its own risks.”
 

[email protected]

The Essure permanent birth control device will no longer be sold or distributed after Dec. 31, 2018, in the United States.

Bayer, the manufacturer of Essure, notified the Food and Drug Administration of its decision to halt U.S. sales of the device, Commissioner Scott Gottlieb, MD, announced July 20 in a press release. Dr. Gottlieb added that the agency would continue its commitment to postmarketing review of Essure. “We expect Bayer to meet its postmarket obligations concerning this device.”

Since its approval, Essure is estimated to have been used by more than 750,000 patients worldwide, the FDA release stated. The device has been associated with serious risks, including persistent pain, perforation of the uterus and fallopian tubes, and migration of the coils into the pelvis or abdomen.

“In April, when the FDA became aware that many patients were not being adequately counseled, we required a restriction, which limits the sale and distribution of the device to only health care providers and facilities that provide information to patients about the risks and benefits of this device and gives patients the opportunity to sign an acknowledgment that they fully understood these potential risks before having the device implanted. Since the FDA ordered Bayer to conduct the postmarket study and then to add a boxed warning and a Patient Decision Checklist to the labeling, there has been an approximate 70% decline in sales of Essure in the United States,” Dr. Gottlieb said in the FDA press release. The company stated its decision to halt sales and distribution of the device was because of commercial reasons.

“Numerous adverse events ... were reported to the FDA, including a significant collection of recent reports that have mentioned issues involving surgery to remove the device. We’re continuing our evaluation of these reports to better understand reasons for the device removal. The agency is committed to continuing to provide updates on our evaluation of this data as the information is collected and we develop new findings about the device.”

In September 2015, the FDA convened an expert panel to examine and follow up on complaints from Essure users that included abdominal pain, abnormal uterine bleeding, and device migration. In February 2016, the FDA ordered Bayer to conduct a postmarket (522) study to better evaluate the safety profile of the device when used in the real world. The following October, the agency issued the final guidance, “Labeling for Permanent Hysteroscopically Placed Tubal Implants Intended for Sterilization.” Soon thereafter, the FDA approved updated labeling for Essure that added a boxed warning and a Patient Decision Checklist.

In March 2018, the FDA reported a rise in new medical device reports submitted to the agency’s public database in 2017, with more than 90% of the reports involving potential device removal. The April restriction of sales and distribution was in response to concerns that not every patient was receiving adequate risk information.

“I want to stress that, even when Essure is no longer sold, the FDA will remain vigilant in protecting patients who’ve already had this device implanted. We’ll continue to monitor adverse events reported to our database, as well as other data sources. And we’ll communicate publicly on any new findings or concerns. The restriction on sale and distribution will remain in place. Regarding the postmarket 522 study, Bayer will continue to enroll new participants. Each study participant will be followed for a total of 3 years, and the company will continue to submit reports to the FDA on the study’s progress and results. Since Bayer will not be able to meet its expected enrollment numbers for this study that relied on enrolling patients who were newly implanted with Essure, we’ll be working with the company to best determine how to move forward to answer the critical questions we posed concerning certain patient complications that may be experienced by patients who have Essure,” Dr. Gottlieb stated.

He added that women who are using Essure successfully to prevent pregnancy should continue to do so, as “device removal has its own risks.”
 

[email protected]

The Essure permanent birth control device will no longer be sold or distributed after Dec. 31, 2018, in the United States.

Bayer, the manufacturer of Essure, notified the Food and Drug Administration of its decision to halt U.S. sales of the device, Commissioner Scott Gottlieb, MD, announced July 20 in a press release. Dr. Gottlieb added that the agency would continue its commitment to postmarketing review of Essure. “We expect Bayer to meet its postmarket obligations concerning this device.”

Since its approval, Essure is estimated to have been used by more than 750,000 patients worldwide, the FDA release stated. The device has been associated with serious risks, including persistent pain, perforation of the uterus and fallopian tubes, and migration of the coils into the pelvis or abdomen.

“In April, when the FDA became aware that many patients were not being adequately counseled, we required a restriction, which limits the sale and distribution of the device to only health care providers and facilities that provide information to patients about the risks and benefits of this device and gives patients the opportunity to sign an acknowledgment that they fully understood these potential risks before having the device implanted. Since the FDA ordered Bayer to conduct the postmarket study and then to add a boxed warning and a Patient Decision Checklist to the labeling, there has been an approximate 70% decline in sales of Essure in the United States,” Dr. Gottlieb said in the FDA press release. The company stated its decision to halt sales and distribution of the device was because of commercial reasons.

“Numerous adverse events ... were reported to the FDA, including a significant collection of recent reports that have mentioned issues involving surgery to remove the device. We’re continuing our evaluation of these reports to better understand reasons for the device removal. The agency is committed to continuing to provide updates on our evaluation of this data as the information is collected and we develop new findings about the device.”

In September 2015, the FDA convened an expert panel to examine and follow up on complaints from Essure users that included abdominal pain, abnormal uterine bleeding, and device migration. In February 2016, the FDA ordered Bayer to conduct a postmarket (522) study to better evaluate the safety profile of the device when used in the real world. The following October, the agency issued the final guidance, “Labeling for Permanent Hysteroscopically Placed Tubal Implants Intended for Sterilization.” Soon thereafter, the FDA approved updated labeling for Essure that added a boxed warning and a Patient Decision Checklist.

In March 2018, the FDA reported a rise in new medical device reports submitted to the agency’s public database in 2017, with more than 90% of the reports involving potential device removal. The April restriction of sales and distribution was in response to concerns that not every patient was receiving adequate risk information.

“I want to stress that, even when Essure is no longer sold, the FDA will remain vigilant in protecting patients who’ve already had this device implanted. We’ll continue to monitor adverse events reported to our database, as well as other data sources. And we’ll communicate publicly on any new findings or concerns. The restriction on sale and distribution will remain in place. Regarding the postmarket 522 study, Bayer will continue to enroll new participants. Each study participant will be followed for a total of 3 years, and the company will continue to submit reports to the FDA on the study’s progress and results. Since Bayer will not be able to meet its expected enrollment numbers for this study that relied on enrolling patients who were newly implanted with Essure, we’ll be working with the company to best determine how to move forward to answer the critical questions we posed concerning certain patient complications that may be experienced by patients who have Essure,” Dr. Gottlieb stated.

He added that women who are using Essure successfully to prevent pregnancy should continue to do so, as “device removal has its own risks.”
 

[email protected]

Ibrutinib has a favorable safety profile in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL), according to findings from a pooled analysis.

Susan M. O’Brien, MD, of the University of California, Irvine, and her colleagues reported pooled data from four randomized, controlled trials that included a 756 patients treated with ibrutinib and 749 patients who received a comparator drug. Patients were treated for either CLL/SLL or MCL, and safety was assessed by comparing crude and exposure-adjusted incidence rates of reported adverse events (AEs).

The comparator drugs included intravenous ofatumumab, oral chlorambucil, intravenous bendamustine plus rituximab, and intravenous temsirolimus.

While adverse event data have been published for each study analyzed, the researchers noted that the pooled analysis allows for an “in-depth assessment of the frequency and severity of both common AEs as well as additional AEs of clinical interest.”

Ibrutinib-treated patients had low rates of treatment discontinuation, compared with comparator-treatment patients (27% vs. 85%), the researchers reported in Clinical Lymphoma, Myeloma & Leukemia. Most discontinuations were caused by disease progression.

In terms of AEs, the types of events reported were similar among the drugs, with the three most common being infections, gastrointestinal disorders, and general disorders/administration-site conditions.

Diarrhea, muscle spasms, and arthralgia were reported more often among ibrutinib-treated patients. The prevalence of the most common all-grade AEs generally decreased over time with ibrutinib, peaking in the first 3 months of treatment. For serious AEs, only atrial fibrillation was higher with ibrutinib than comparator drugs when adjusted for exposure.

[email protected]

SOURCE: O’Brien SM et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 27. doi: 10.1016/j.clml.2018.06.016.

Ibrutinib has a favorable safety profile in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL), according to findings from a pooled analysis.

Susan M. O’Brien, MD, of the University of California, Irvine, and her colleagues reported pooled data from four randomized, controlled trials that included a 756 patients treated with ibrutinib and 749 patients who received a comparator drug. Patients were treated for either CLL/SLL or MCL, and safety was assessed by comparing crude and exposure-adjusted incidence rates of reported adverse events (AEs).

The comparator drugs included intravenous ofatumumab, oral chlorambucil, intravenous bendamustine plus rituximab, and intravenous temsirolimus.

While adverse event data have been published for each study analyzed, the researchers noted that the pooled analysis allows for an “in-depth assessment of the frequency and severity of both common AEs as well as additional AEs of clinical interest.”

Ibrutinib-treated patients had low rates of treatment discontinuation, compared with comparator-treatment patients (27% vs. 85%), the researchers reported in Clinical Lymphoma, Myeloma & Leukemia. Most discontinuations were caused by disease progression.

In terms of AEs, the types of events reported were similar among the drugs, with the three most common being infections, gastrointestinal disorders, and general disorders/administration-site conditions.

Diarrhea, muscle spasms, and arthralgia were reported more often among ibrutinib-treated patients. The prevalence of the most common all-grade AEs generally decreased over time with ibrutinib, peaking in the first 3 months of treatment. For serious AEs, only atrial fibrillation was higher with ibrutinib than comparator drugs when adjusted for exposure.

[email protected]

SOURCE: O’Brien SM et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 27. doi: 10.1016/j.clml.2018.06.016.

Ibrutinib has a favorable safety profile in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL), according to findings from a pooled analysis.

Susan M. O’Brien, MD, of the University of California, Irvine, and her colleagues reported pooled data from four randomized, controlled trials that included a 756 patients treated with ibrutinib and 749 patients who received a comparator drug. Patients were treated for either CLL/SLL or MCL, and safety was assessed by comparing crude and exposure-adjusted incidence rates of reported adverse events (AEs).

The comparator drugs included intravenous ofatumumab, oral chlorambucil, intravenous bendamustine plus rituximab, and intravenous temsirolimus.

While adverse event data have been published for each study analyzed, the researchers noted that the pooled analysis allows for an “in-depth assessment of the frequency and severity of both common AEs as well as additional AEs of clinical interest.”

Ibrutinib-treated patients had low rates of treatment discontinuation, compared with comparator-treatment patients (27% vs. 85%), the researchers reported in Clinical Lymphoma, Myeloma & Leukemia. Most discontinuations were caused by disease progression.

In terms of AEs, the types of events reported were similar among the drugs, with the three most common being infections, gastrointestinal disorders, and general disorders/administration-site conditions.

Diarrhea, muscle spasms, and arthralgia were reported more often among ibrutinib-treated patients. The prevalence of the most common all-grade AEs generally decreased over time with ibrutinib, peaking in the first 3 months of treatment. For serious AEs, only atrial fibrillation was higher with ibrutinib than comparator drugs when adjusted for exposure.

[email protected]

SOURCE: O’Brien SM et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 27. doi: 10.1016/j.clml.2018.06.016.

ABSTRACT

Vascular injury to the popliteal artery during knee surgery is uncommon, but it has significant consequences not only for the patient but also to the surgeon since it poses the threat of malpractice litigation. The vascular anatomy of the lower extremity is variable especially when it involves both the popliteal artery and its branches. An aberrant vascular course may increase the risk of iatrogenic vascular injury during surgery. Careful preoperative planning with advanced imaging can decrease the risk of a devastating vascular injury.

Continue to: Most non-traumatic injuries...

Most non-traumatic injuries to the popliteal artery are iatrogenic and may occur during total knee replacement,^1-8 high tibial osteotomy,^2,3,5-7 anterior cruciate ligament reconstruction,^2,6 posterior cruciate ligament reconstruction,^2,6,9,10 and arthroscopic meniscectomy.^2,6,9 Despite the rare occurrence of complications involving the popliteal artery during such procedures, results of vessel injuries can be devastating and may also lead to malpractice litigation. Anatomic variations of the distal popliteal artery and its significance in surgery have been well documented in the literature.^2-6,8,11 However, due to lack of awareness, this issue is often unintentionally disregarded. We present the case of an aberrant anterior tibial artery that was found during the review of a magnetic resonance imaging study. The patient was provided written informed consent for print and electronic publication of this case report.

CASE

A 61-year-old woman presented with a history of right knee pain from osteoarthritis that had rapidly progressed over 1 week secondary to a fall. The patient had no history of previous knee surgery. After careful evaluation of her right knee pain, treatment options were discussed. The patient agreed to proceed with total knee arthroplasty (TKA). During preoperative planning, the patient’s previous magnetic resonance imaging (MRI) was reviewed. The MRI study revealed an aberrant anterior tibial artery. The popliteal artery bifurcated at the level of the knee joint (Figures 1A-1C). After the bifurcation, the anterior tibial artery coursed anteriorly to the tibioperoneal trunk. The anterior tibial artery is seen just anterior to the popliteus muscle and just posterior to the tibial plateau cortex (Figure 2). Intraoperatively, an oscillating saw was utilized for the tibial cut. Care was taken not to penetrate the posterior cortex. An osteotome was used to elevate the tibial cut and hinge it open, and with a small mallet, finish the tibial cut. The patient had a successful TKA without complication.

DISCUSSION

Emerging from the adductor hiatus (Hunter’s canal), the normal course of the popliteal artery is a position slightly lateral in the intercondylar fossa. It courses obliquely and posteriorly to the popliteus then bifurcates into the anterior tibial artery and the tibioperoneal trunk at the inferior border of the popliteus. The tibioperoneal trunk bifurcates into both the posterior tibial artery and the peroneal artery at the proximal tibia well below the knee joint.

There are many reported cases of popliteal artery variations.^{2,3,6,7,9,11-13} Variations in the popliteal artery are consequences of persistent embryonic vessels from primitive segments of the artery or abnormal fusions among them.¹⁴ According to Kim and colleagues,¹¹ variations can be classified by the modified Lippert’s system. This system has 3 categories with 3 subtypes (Table). Variations are not uncommon and occur in 7.4% to 12% of the population.^2,4,5,7,13

Table. Modified Lippert’s System¹¹

Of these variations, type IIA, a high bifurcation of the anterior tibial artery, arising at or above the knee joint from the popliteal artery is the most significant. Forty-two percent of these vessels course anterior to the popliteus and make direct contact with the cortex of the posterior tibia.⁴ It is also the most frequent variant type reported in 1.2% to 6% of the population.^3,7,11-13

Continue to: Injury to the popliteal artery...

Injury to the popliteal artery during an orthopedic procedure is believed to be under reported⁶ but is considered a rare complication. The incidence of popliteal artery injury in TKA is thought to be 0.03% to 0.2%.^1,2,5,7,8 Vessel injury in both high tibial osteotomy and arthroscopic surgeries (lateral meniscal repair) have also been reported.^5,6,8,10 Despite the rare occurrence of this complication, it may have devastating outcomes. The injury can be repaired with vascular grafting depending on its severity; however, it could also lead to compartment syndrome, loss of function, chronic ulcers, and necrosis of the affected limb resulting in below the knee amputation. The current consensus is that the popliteal artery moves posteriorly away from the tibia when the knee is in 90^° of flexion,⁵ which is the standard position for many orthopedic knee surgeries. This position limits the risk of injuring the vessel. However, Metzdorf and colleagues,⁴ Smith and colleagues,⁶ and Zaidi and colleagues⁸ suggested that the vessel not be displaced posteriorly with flexion. These studies reported that the behavior of the popliteal artery varied among individuals since in some cases it had moved closer to the tibia in flexion when compared with extension.

Regardless of the behavior of the artery, it is protected by the popliteus muscle in most orthopedic knee surgeries since the majority course posterior to the muscle. However, in cases of Lippert’s type IIA variation, it not only loses protection as it courses beneath the popliteus but also is extremely vulnerable from the close relationship to the posterior tibial cortex. Klecker and colleagues² described the aberrant artery locations related to common orthopedic procedures, which demonstrated its close proximity to various surgical plane levels. The position of the aberrant artery is approximately 1 to 1.5 cm distal to the posterior tibial joint line, just posterior to the posterior capsule, and close to the posterior cruciate ligament insertion site where the transverse tibial cut is made during TKA. This location also corresponds to the position for an inlay block and the tibial tunnel for posterior cruciate ligament reconstruction. A transverse cut for a high tibial osteotomy is approximately 1.5 to 2.5 cm distal to the posterior tibial joint line; the aberrant artery appeared directly posterior to the tibial cortex. These relationships were equivalent findings in this case. Such relationships of the aberrant anterior tibial artery to both the posterior tibial cortex and the posterior capsule increase the risk of vessel (anterior tibial artery) injury intraoperatively. The risk further increases in a revision of total knee replacement. This is secondary to limited flexibility of the vessel from scar formation which requires a more distal incision.^1,4

CONCLUSION

Vascular injuries in knee surgeries are rare and often overlooked. Despite their low occurrence rate, outcomes of these injuries have grave consequences not only regarding medical but also legal matters. Variations in the popliteal artery are not uncommon and could potentially contribute to risks of vessel injury. Of these variations, the high originating anterior tibial artery poses a special risk. However, due to the low occurrence rate of these injuries, screening the general population may not be cost-effective. Since many patients already have obtained necessary imaging (preferably MRI), a careful review of these images along with preoperative planning and special care during surgery is recommended to identify popliteal artery variants and avoid iatrogenic vascular injury.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Vascular injury to the popliteal artery during knee surgery is uncommon, but it has significant consequences not only for the patient but also to the surgeon since it poses the threat of malpractice litigation. The vascular anatomy of the lower extremity is variable especially when it involves both the popliteal artery and its branches. An aberrant vascular course may increase the risk of iatrogenic vascular injury during surgery. Careful preoperative planning with advanced imaging can decrease the risk of a devastating vascular injury.

Continue to: Most non-traumatic injuries...

Most non-traumatic injuries to the popliteal artery are iatrogenic and may occur during total knee replacement,^1-8 high tibial osteotomy,^2,3,5-7 anterior cruciate ligament reconstruction,^2,6 posterior cruciate ligament reconstruction,^2,6,9,10 and arthroscopic meniscectomy.^2,6,9 Despite the rare occurrence of complications involving the popliteal artery during such procedures, results of vessel injuries can be devastating and may also lead to malpractice litigation. Anatomic variations of the distal popliteal artery and its significance in surgery have been well documented in the literature.^2-6,8,11 However, due to lack of awareness, this issue is often unintentionally disregarded. We present the case of an aberrant anterior tibial artery that was found during the review of a magnetic resonance imaging study. The patient was provided written informed consent for print and electronic publication of this case report.

CASE

A 61-year-old woman presented with a history of right knee pain from osteoarthritis that had rapidly progressed over 1 week secondary to a fall. The patient had no history of previous knee surgery. After careful evaluation of her right knee pain, treatment options were discussed. The patient agreed to proceed with total knee arthroplasty (TKA). During preoperative planning, the patient’s previous magnetic resonance imaging (MRI) was reviewed. The MRI study revealed an aberrant anterior tibial artery. The popliteal artery bifurcated at the level of the knee joint (Figures 1A-1C). After the bifurcation, the anterior tibial artery coursed anteriorly to the tibioperoneal trunk. The anterior tibial artery is seen just anterior to the popliteus muscle and just posterior to the tibial plateau cortex (Figure 2). Intraoperatively, an oscillating saw was utilized for the tibial cut. Care was taken not to penetrate the posterior cortex. An osteotome was used to elevate the tibial cut and hinge it open, and with a small mallet, finish the tibial cut. The patient had a successful TKA without complication.

DISCUSSION

Emerging from the adductor hiatus (Hunter’s canal), the normal course of the popliteal artery is a position slightly lateral in the intercondylar fossa. It courses obliquely and posteriorly to the popliteus then bifurcates into the anterior tibial artery and the tibioperoneal trunk at the inferior border of the popliteus. The tibioperoneal trunk bifurcates into both the posterior tibial artery and the peroneal artery at the proximal tibia well below the knee joint.

There are many reported cases of popliteal artery variations.^{2,3,6,7,9,11-13} Variations in the popliteal artery are consequences of persistent embryonic vessels from primitive segments of the artery or abnormal fusions among them.¹⁴ According to Kim and colleagues,¹¹ variations can be classified by the modified Lippert’s system. This system has 3 categories with 3 subtypes (Table). Variations are not uncommon and occur in 7.4% to 12% of the population.^2,4,5,7,13

Table. Modified Lippert’s System¹¹

Of these variations, type IIA, a high bifurcation of the anterior tibial artery, arising at or above the knee joint from the popliteal artery is the most significant. Forty-two percent of these vessels course anterior to the popliteus and make direct contact with the cortex of the posterior tibia.⁴ It is also the most frequent variant type reported in 1.2% to 6% of the population.^3,7,11-13

Continue to: Injury to the popliteal artery...

Injury to the popliteal artery during an orthopedic procedure is believed to be under reported⁶ but is considered a rare complication. The incidence of popliteal artery injury in TKA is thought to be 0.03% to 0.2%.^1,2,5,7,8 Vessel injury in both high tibial osteotomy and arthroscopic surgeries (lateral meniscal repair) have also been reported.^5,6,8,10 Despite the rare occurrence of this complication, it may have devastating outcomes. The injury can be repaired with vascular grafting depending on its severity; however, it could also lead to compartment syndrome, loss of function, chronic ulcers, and necrosis of the affected limb resulting in below the knee amputation. The current consensus is that the popliteal artery moves posteriorly away from the tibia when the knee is in 90^° of flexion,⁵ which is the standard position for many orthopedic knee surgeries. This position limits the risk of injuring the vessel. However, Metzdorf and colleagues,⁴ Smith and colleagues,⁶ and Zaidi and colleagues⁸ suggested that the vessel not be displaced posteriorly with flexion. These studies reported that the behavior of the popliteal artery varied among individuals since in some cases it had moved closer to the tibia in flexion when compared with extension.

Regardless of the behavior of the artery, it is protected by the popliteus muscle in most orthopedic knee surgeries since the majority course posterior to the muscle. However, in cases of Lippert’s type IIA variation, it not only loses protection as it courses beneath the popliteus but also is extremely vulnerable from the close relationship to the posterior tibial cortex. Klecker and colleagues² described the aberrant artery locations related to common orthopedic procedures, which demonstrated its close proximity to various surgical plane levels. The position of the aberrant artery is approximately 1 to 1.5 cm distal to the posterior tibial joint line, just posterior to the posterior capsule, and close to the posterior cruciate ligament insertion site where the transverse tibial cut is made during TKA. This location also corresponds to the position for an inlay block and the tibial tunnel for posterior cruciate ligament reconstruction. A transverse cut for a high tibial osteotomy is approximately 1.5 to 2.5 cm distal to the posterior tibial joint line; the aberrant artery appeared directly posterior to the tibial cortex. These relationships were equivalent findings in this case. Such relationships of the aberrant anterior tibial artery to both the posterior tibial cortex and the posterior capsule increase the risk of vessel (anterior tibial artery) injury intraoperatively. The risk further increases in a revision of total knee replacement. This is secondary to limited flexibility of the vessel from scar formation which requires a more distal incision.^1,4

CONCLUSION

Vascular injuries in knee surgeries are rare and often overlooked. Despite their low occurrence rate, outcomes of these injuries have grave consequences not only regarding medical but also legal matters. Variations in the popliteal artery are not uncommon and could potentially contribute to risks of vessel injury. Of these variations, the high originating anterior tibial artery poses a special risk. However, due to the low occurrence rate of these injuries, screening the general population may not be cost-effective. Since many patients already have obtained necessary imaging (preferably MRI), a careful review of these images along with preoperative planning and special care during surgery is recommended to identify popliteal artery variants and avoid iatrogenic vascular injury.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Vascular injury to the popliteal artery during knee surgery is uncommon, but it has significant consequences not only for the patient but also to the surgeon since it poses the threat of malpractice litigation. The vascular anatomy of the lower extremity is variable especially when it involves both the popliteal artery and its branches. An aberrant vascular course may increase the risk of iatrogenic vascular injury during surgery. Careful preoperative planning with advanced imaging can decrease the risk of a devastating vascular injury.

Continue to: Most non-traumatic injuries...

Most non-traumatic injuries to the popliteal artery are iatrogenic and may occur during total knee replacement,^1-8 high tibial osteotomy,^2,3,5-7 anterior cruciate ligament reconstruction,^2,6 posterior cruciate ligament reconstruction,^2,6,9,10 and arthroscopic meniscectomy.^2,6,9 Despite the rare occurrence of complications involving the popliteal artery during such procedures, results of vessel injuries can be devastating and may also lead to malpractice litigation. Anatomic variations of the distal popliteal artery and its significance in surgery have been well documented in the literature.^2-6,8,11 However, due to lack of awareness, this issue is often unintentionally disregarded. We present the case of an aberrant anterior tibial artery that was found during the review of a magnetic resonance imaging study. The patient was provided written informed consent for print and electronic publication of this case report.

CASE

A 61-year-old woman presented with a history of right knee pain from osteoarthritis that had rapidly progressed over 1 week secondary to a fall. The patient had no history of previous knee surgery. After careful evaluation of her right knee pain, treatment options were discussed. The patient agreed to proceed with total knee arthroplasty (TKA). During preoperative planning, the patient’s previous magnetic resonance imaging (MRI) was reviewed. The MRI study revealed an aberrant anterior tibial artery. The popliteal artery bifurcated at the level of the knee joint (Figures 1A-1C). After the bifurcation, the anterior tibial artery coursed anteriorly to the tibioperoneal trunk. The anterior tibial artery is seen just anterior to the popliteus muscle and just posterior to the tibial plateau cortex (Figure 2). Intraoperatively, an oscillating saw was utilized for the tibial cut. Care was taken not to penetrate the posterior cortex. An osteotome was used to elevate the tibial cut and hinge it open, and with a small mallet, finish the tibial cut. The patient had a successful TKA without complication.

DISCUSSION

Emerging from the adductor hiatus (Hunter’s canal), the normal course of the popliteal artery is a position slightly lateral in the intercondylar fossa. It courses obliquely and posteriorly to the popliteus then bifurcates into the anterior tibial artery and the tibioperoneal trunk at the inferior border of the popliteus. The tibioperoneal trunk bifurcates into both the posterior tibial artery and the peroneal artery at the proximal tibia well below the knee joint.

There are many reported cases of popliteal artery variations.^{2,3,6,7,9,11-13} Variations in the popliteal artery are consequences of persistent embryonic vessels from primitive segments of the artery or abnormal fusions among them.¹⁴ According to Kim and colleagues,¹¹ variations can be classified by the modified Lippert’s system. This system has 3 categories with 3 subtypes (Table). Variations are not uncommon and occur in 7.4% to 12% of the population.^2,4,5,7,13

Table. Modified Lippert’s System¹¹

Of these variations, type IIA, a high bifurcation of the anterior tibial artery, arising at or above the knee joint from the popliteal artery is the most significant. Forty-two percent of these vessels course anterior to the popliteus and make direct contact with the cortex of the posterior tibia.⁴ It is also the most frequent variant type reported in 1.2% to 6% of the population.^3,7,11-13

Continue to: Injury to the popliteal artery...

Injury to the popliteal artery during an orthopedic procedure is believed to be under reported⁶ but is considered a rare complication. The incidence of popliteal artery injury in TKA is thought to be 0.03% to 0.2%.^1,2,5,7,8 Vessel injury in both high tibial osteotomy and arthroscopic surgeries (lateral meniscal repair) have also been reported.^5,6,8,10 Despite the rare occurrence of this complication, it may have devastating outcomes. The injury can be repaired with vascular grafting depending on its severity; however, it could also lead to compartment syndrome, loss of function, chronic ulcers, and necrosis of the affected limb resulting in below the knee amputation. The current consensus is that the popliteal artery moves posteriorly away from the tibia when the knee is in 90^° of flexion,⁵ which is the standard position for many orthopedic knee surgeries. This position limits the risk of injuring the vessel. However, Metzdorf and colleagues,⁴ Smith and colleagues,⁶ and Zaidi and colleagues⁸ suggested that the vessel not be displaced posteriorly with flexion. These studies reported that the behavior of the popliteal artery varied among individuals since in some cases it had moved closer to the tibia in flexion when compared with extension.

Regardless of the behavior of the artery, it is protected by the popliteus muscle in most orthopedic knee surgeries since the majority course posterior to the muscle. However, in cases of Lippert’s type IIA variation, it not only loses protection as it courses beneath the popliteus but also is extremely vulnerable from the close relationship to the posterior tibial cortex. Klecker and colleagues² described the aberrant artery locations related to common orthopedic procedures, which demonstrated its close proximity to various surgical plane levels. The position of the aberrant artery is approximately 1 to 1.5 cm distal to the posterior tibial joint line, just posterior to the posterior capsule, and close to the posterior cruciate ligament insertion site where the transverse tibial cut is made during TKA. This location also corresponds to the position for an inlay block and the tibial tunnel for posterior cruciate ligament reconstruction. A transverse cut for a high tibial osteotomy is approximately 1.5 to 2.5 cm distal to the posterior tibial joint line; the aberrant artery appeared directly posterior to the tibial cortex. These relationships were equivalent findings in this case. Such relationships of the aberrant anterior tibial artery to both the posterior tibial cortex and the posterior capsule increase the risk of vessel (anterior tibial artery) injury intraoperatively. The risk further increases in a revision of total knee replacement. This is secondary to limited flexibility of the vessel from scar formation which requires a more distal incision.^1,4

CONCLUSION

Vascular injuries in knee surgeries are rare and often overlooked. Despite their low occurrence rate, outcomes of these injuries have grave consequences not only regarding medical but also legal matters. Variations in the popliteal artery are not uncommon and could potentially contribute to risks of vessel injury. Of these variations, the high originating anterior tibial artery poses a special risk. However, due to the low occurrence rate of these injuries, screening the general population may not be cost-effective. Since many patients already have obtained necessary imaging (preferably MRI), a careful review of these images along with preoperative planning and special care during surgery is recommended to identify popliteal artery variants and avoid iatrogenic vascular injury.

This paper will be judged for the Resident Writer’s Award.

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

In 2012, a study conducted by Zullig and colleagues revealed that about 40,000 cancer cases are reported annually to the Veterans Affairs Central Cancer Registry.¹ This represented about 3% of all cancer cases in the US. Within the VA patient population, the most commonly diagnosed cancers are prostate, lung and bronchial, colorectal, urinary and bladder cancers, and skin melanomas. This mirrors the commonly diagnosed cancers within the total US patient population.

Click here to continue reading.

In 2012, a study conducted by Zullig and colleagues revealed that about 40,000 cancer cases are reported annually to the Veterans Affairs Central Cancer Registry.¹ This represented about 3% of all cancer cases in the US. Within the VA patient population, the most commonly diagnosed cancers are prostate, lung and bronchial, colorectal, urinary and bladder cancers, and skin melanomas. This mirrors the commonly diagnosed cancers within the total US patient population.

Click here to continue reading.

In 2012, a study conducted by Zullig and colleagues revealed that about 40,000 cancer cases are reported annually to the Veterans Affairs Central Cancer Registry.¹ This represented about 3% of all cancer cases in the US. Within the VA patient population, the most commonly diagnosed cancers are prostate, lung and bronchial, colorectal, urinary and bladder cancers, and skin melanomas. This mirrors the commonly diagnosed cancers within the total US patient population.

Click here to continue reading.