An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

Even as summer continues on, the long, hot, sunny days and backyard barbecues can be tinged with the realization that the new school year looms ahead. For those in traditional school systems, September is the return to the classroom. This has long been a source of angst for many children who may face a new school or a return to the challenging, even overwhelming, business of learning.

“The end of summer and the beginning of a new school year can be a stressful time for parents and children,” says psychologist Lynn Bufka, PhD, assistant execute director for practice, research, and policy for the American Psychological Association. “While trying to manage work and the household, parents can sometimes overlook their children’s feelings of nervousness or anxiety as school begins. Working with your children to build resilience and manage their emotions can be beneficial for the psychological health of the whole family.”

According to the association, parents can help ease their child’s worries by offering support and encouragement and by listening to their child’s concerns, which can help foster their resilience. A dry run about a week before the big day can help reset the summer sleep schedule. Getting school supplies together and ready for action is another bit of preparation that helps get the mind ready for the reality of school. Visiting a new school, if permitted, can remove some sense of the unknown and lay the path for that first day through the front door. Empathy can be a powerful aid; understanding that a child might be apprehensive can prevent the potentially misguided advice to just tough it out.

But children aren’t the only ones with back-to-school anxiety. Increasingly, this time of year is generating stress for parents. When budgets are stretched tight, the additional school expenses can be a strain. The horrors of school shooting incidents can be on parents’ minds, especially when their child is enrolled in a new and unfamiliar school. An era of heightened competitiveness for postsecondary education and scholarship money comes with the baggage of worry that a son or daughter is lagging and already might be behind the eight ball in the game of life.

Parental stress can be tough to deal with. Budget planning, participating in safe-school activities, fostering relationships with teachers and staff, having a heightened awareness of signs of school-related stress in their children, and maintaining faith in their children’s ability to learn and succeed can go a long way toward easing the parental burden.

Click here to read the APA’s back-to-school tips.

Even as summer continues on, the long, hot, sunny days and backyard barbecues can be tinged with the realization that the new school year looms ahead. For those in traditional school systems, September is the return to the classroom. This has long been a source of angst for many children who may face a new school or a return to the challenging, even overwhelming, business of learning.

“The end of summer and the beginning of a new school year can be a stressful time for parents and children,” says psychologist Lynn Bufka, PhD, assistant execute director for practice, research, and policy for the American Psychological Association. “While trying to manage work and the household, parents can sometimes overlook their children’s feelings of nervousness or anxiety as school begins. Working with your children to build resilience and manage their emotions can be beneficial for the psychological health of the whole family.”

According to the association, parents can help ease their child’s worries by offering support and encouragement and by listening to their child’s concerns, which can help foster their resilience. A dry run about a week before the big day can help reset the summer sleep schedule. Getting school supplies together and ready for action is another bit of preparation that helps get the mind ready for the reality of school. Visiting a new school, if permitted, can remove some sense of the unknown and lay the path for that first day through the front door. Empathy can be a powerful aid; understanding that a child might be apprehensive can prevent the potentially misguided advice to just tough it out.

But children aren’t the only ones with back-to-school anxiety. Increasingly, this time of year is generating stress for parents. When budgets are stretched tight, the additional school expenses can be a strain. The horrors of school shooting incidents can be on parents’ minds, especially when their child is enrolled in a new and unfamiliar school. An era of heightened competitiveness for postsecondary education and scholarship money comes with the baggage of worry that a son or daughter is lagging and already might be behind the eight ball in the game of life.

Parental stress can be tough to deal with. Budget planning, participating in safe-school activities, fostering relationships with teachers and staff, having a heightened awareness of signs of school-related stress in their children, and maintaining faith in their children’s ability to learn and succeed can go a long way toward easing the parental burden.

Click here to read the APA’s back-to-school tips.

Even as summer continues on, the long, hot, sunny days and backyard barbecues can be tinged with the realization that the new school year looms ahead. For those in traditional school systems, September is the return to the classroom. This has long been a source of angst for many children who may face a new school or a return to the challenging, even overwhelming, business of learning.

“The end of summer and the beginning of a new school year can be a stressful time for parents and children,” says psychologist Lynn Bufka, PhD, assistant execute director for practice, research, and policy for the American Psychological Association. “While trying to manage work and the household, parents can sometimes overlook their children’s feelings of nervousness or anxiety as school begins. Working with your children to build resilience and manage their emotions can be beneficial for the psychological health of the whole family.”

According to the association, parents can help ease their child’s worries by offering support and encouragement and by listening to their child’s concerns, which can help foster their resilience. A dry run about a week before the big day can help reset the summer sleep schedule. Getting school supplies together and ready for action is another bit of preparation that helps get the mind ready for the reality of school. Visiting a new school, if permitted, can remove some sense of the unknown and lay the path for that first day through the front door. Empathy can be a powerful aid; understanding that a child might be apprehensive can prevent the potentially misguided advice to just tough it out.

But children aren’t the only ones with back-to-school anxiety. Increasingly, this time of year is generating stress for parents. When budgets are stretched tight, the additional school expenses can be a strain. The horrors of school shooting incidents can be on parents’ minds, especially when their child is enrolled in a new and unfamiliar school. An era of heightened competitiveness for postsecondary education and scholarship money comes with the baggage of worry that a son or daughter is lagging and already might be behind the eight ball in the game of life.

Parental stress can be tough to deal with. Budget planning, participating in safe-school activities, fostering relationships with teachers and staff, having a heightened awareness of signs of school-related stress in their children, and maintaining faith in their children’s ability to learn and succeed can go a long way toward easing the parental burden.

Click here to read the APA’s back-to-school tips.

Physicians take the “first do no harm” aphorism seriously. Still, as humans, their biases and opinions can – and do – cause harm. An example, according to an opinion piece written in the Globe and Mail, is the way physicians sometimes treat women who are overweight.

The article cites an Alabama woman named Kayla Rahm, whose complaints of weight gain, abdominal swelling, and shortness of breath fell on the deaf ears of four doctors who, instead of getting to the bottom of her problem, pointed to her weight as the culprit. Ultimately, she had a 50-pound ovarian cyst removed (thankfully, benign.)

“She was seeking help from multiple physicians, and we had missed it – as a medical community, we had missed it,” said Gregory Jones, DO, the obstetrician-gynecologist who performed the eventual surgery, in an interview with the Washington Post.

The weight-related rebuff is all too common for women. The consequences can be tragic. Consider Ellen Maud Bennett, a Canadian woman whose complaints of ill health stretching back years had been met with suggestions to lose weight. All the while, cancer was developing, and when the truth was finally recognized, it was too late.

Her obituary offered this poignant message: “A final message Ellen wanted to share was about the fat shaming she endured from the medical profession. Over the past few years of feeling unwell, she sought out medical intervention and no one offered any support or suggestions beyond weight loss. Ellen’s dying wish was that women of size make her death matter by advocating strongly for their health and not accepting that fat is the only relevant health issue.”

Overweight women are reportedly less likely to be referred for cervical and breast-cancer screenings. Fat shaming can dissuade women from seeking medical help. Instead, they can buy into the view that their health problems are self-imposed.

A recent study conducted in Canada involving more than 54,000 clinically obese people, some with metabolic risk factors and others were who just obese, found that those with no metabolic risk factors were no more likely to die than people of lower weight. “This means that hundreds of thousands of people in North America alone with metabolically healthy obesity will be told to lose weight when it’s questionable how much benefit they’ll actually receive ,” head researcher Jennifer L. Kuk, PhD, said in an interview with Science Daily.

Click here to read about Dr. Kuk’s study.
 

Physicians take the “first do no harm” aphorism seriously. Still, as humans, their biases and opinions can – and do – cause harm. An example, according to an opinion piece written in the Globe and Mail, is the way physicians sometimes treat women who are overweight.

The article cites an Alabama woman named Kayla Rahm, whose complaints of weight gain, abdominal swelling, and shortness of breath fell on the deaf ears of four doctors who, instead of getting to the bottom of her problem, pointed to her weight as the culprit. Ultimately, she had a 50-pound ovarian cyst removed (thankfully, benign.)

“She was seeking help from multiple physicians, and we had missed it – as a medical community, we had missed it,” said Gregory Jones, DO, the obstetrician-gynecologist who performed the eventual surgery, in an interview with the Washington Post.

The weight-related rebuff is all too common for women. The consequences can be tragic. Consider Ellen Maud Bennett, a Canadian woman whose complaints of ill health stretching back years had been met with suggestions to lose weight. All the while, cancer was developing, and when the truth was finally recognized, it was too late.

Her obituary offered this poignant message: “A final message Ellen wanted to share was about the fat shaming she endured from the medical profession. Over the past few years of feeling unwell, she sought out medical intervention and no one offered any support or suggestions beyond weight loss. Ellen’s dying wish was that women of size make her death matter by advocating strongly for their health and not accepting that fat is the only relevant health issue.”

Overweight women are reportedly less likely to be referred for cervical and breast-cancer screenings. Fat shaming can dissuade women from seeking medical help. Instead, they can buy into the view that their health problems are self-imposed.

A recent study conducted in Canada involving more than 54,000 clinically obese people, some with metabolic risk factors and others were who just obese, found that those with no metabolic risk factors were no more likely to die than people of lower weight. “This means that hundreds of thousands of people in North America alone with metabolically healthy obesity will be told to lose weight when it’s questionable how much benefit they’ll actually receive ,” head researcher Jennifer L. Kuk, PhD, said in an interview with Science Daily.

Click here to read about Dr. Kuk’s study.
 

Physicians take the “first do no harm” aphorism seriously. Still, as humans, their biases and opinions can – and do – cause harm. An example, according to an opinion piece written in the Globe and Mail, is the way physicians sometimes treat women who are overweight.

The article cites an Alabama woman named Kayla Rahm, whose complaints of weight gain, abdominal swelling, and shortness of breath fell on the deaf ears of four doctors who, instead of getting to the bottom of her problem, pointed to her weight as the culprit. Ultimately, she had a 50-pound ovarian cyst removed (thankfully, benign.)

“She was seeking help from multiple physicians, and we had missed it – as a medical community, we had missed it,” said Gregory Jones, DO, the obstetrician-gynecologist who performed the eventual surgery, in an interview with the Washington Post.

The weight-related rebuff is all too common for women. The consequences can be tragic. Consider Ellen Maud Bennett, a Canadian woman whose complaints of ill health stretching back years had been met with suggestions to lose weight. All the while, cancer was developing, and when the truth was finally recognized, it was too late.

Her obituary offered this poignant message: “A final message Ellen wanted to share was about the fat shaming she endured from the medical profession. Over the past few years of feeling unwell, she sought out medical intervention and no one offered any support or suggestions beyond weight loss. Ellen’s dying wish was that women of size make her death matter by advocating strongly for their health and not accepting that fat is the only relevant health issue.”

Overweight women are reportedly less likely to be referred for cervical and breast-cancer screenings. Fat shaming can dissuade women from seeking medical help. Instead, they can buy into the view that their health problems are self-imposed.

A recent study conducted in Canada involving more than 54,000 clinically obese people, some with metabolic risk factors and others were who just obese, found that those with no metabolic risk factors were no more likely to die than people of lower weight. “This means that hundreds of thousands of people in North America alone with metabolically healthy obesity will be told to lose weight when it’s questionable how much benefit they’ll actually receive ,” head researcher Jennifer L. Kuk, PhD, said in an interview with Science Daily.

Click here to read about Dr. Kuk’s study.
 

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

CORONADO, CALIF. – Preexisting subfertility appears to account for many, but not all, of the adverse outcomes associated with assisted reproductive technology (ART).

©ktsimage/iStockphoto.com

In addition, multiples conceived using ART – including twins – continue to be the biggest preventable risk factor for adverse pregnancy and fetal outcomes.

Those are key points that Joseph C. Gambone, DO, MPH, made during a wide-ranging talk about the adverse pregnancy and fetal outcomes related to ART at a meeting on in vitro fertilization (IVF) and embryo transfer sponsored by the University of California, San Diego.

In 2016, Barbara Luke, ScD, MPH, and her colleagues published results from the ongoing Massachusetts Outcomes Study of Reproductive Technologies (J Reprod Med. 2016 Mar-Apr;61[3-4]:114-27). They found that pregnancy plurality is the predominant risk factor for infants and mothers. Of 8,948 birth outcomes resulting from ART, risks for pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, birth defects, and small for gestational age were significantly increased among twins.

“Lowering the plurality rate, including twins, should substantially reduce morbidity with ART,” said Dr. Gambone, professor emeritus at the David Geffen School of Medicine at the University of California, Los Angeles, who was not affiliated with the study. Thawed embryos were associated with a higher risk for pregnancy-induced hypertension and large for gestational age offspring, but a lower risk for low birth weight and small for gestational age.

According to data from the Society for Assisted Reproductive Technology, elective singleton embryo transfer increased from 35% of all cycles in 2015 to 42% in 2016, while singleton births increased from 80.5% to 84% during the same time period. In addition, the proportion of twins born in 2015 was 19% and declined to 16% in 2016, while the percentage of triplets or greater born was the same in both years (0.4%).

Meanwhile, in an analysis of more than 1.1 million cycles between 2000 and 2011 drawn from Centers for Disease Control and Prevention surveillance data, researchers found that the most commonly reported patient complication was ovarian hyperstimulation syndrome (a peak of 154 per 10,000 autologous cycles) and hospitalization (a peak of 35 per 10,000 autologous cycles; JAMA. 2015 Jan 6;313[1]:88-90). Other complications remained below 10 per 10,000 cycles and included infection, hemorrhage with transfusion, adverse event from medication, adverse event to anesthesia, and patient death. In all, 58 deaths were reported: 18 because of stimulation and 40 during pregnancy. “Some deaths were due to potentially preventable complications because of unrecognized comorbidities or conditions,” said Dr. Gambone, who was not affiliated with the study. “Women with Turner syndrome who receive donor embryos could be an example.”

Today, the most feared maternal and pregnancy outcome from ART is breast and ovarian cancer from treatment, he said, while the most feared outcome in offspring is birth defects from treatment. On the breast cancer front, an analysis of nearly 2 million women provided some reassurance (Fertil Steril. 2017 Jul;108:137-44). It found no increased risk of breast cancer in women who have birth after ART, compared with women who gave birth after spontaneous conception (adjusted hazard ratio, 0.84). It also found no increased risk in women who received ovarian stimulation or other hormonal treatment for infertility (HRs, 0.86 and 0.79, respectively). A smaller study with a median follow-up of 21 years found no difference in the rate of invasive and in situ breast cancer between women who received IVF treatment and those who did not (JAMA. 2016 Jul 19;316[3]:300-12). However, a recent analysis from Great Britain found a slight increase for in situ breast cancer that was associated with women who had a higher number of treatment cycles (BMJ. 2018;362:k2644).

On the ovarian cancer front, a case-control analysis of 1,900 women conducted by researchers at Mayo Clinic found that infertile women who used fertility drugs were not at increased risk of developing ovarian tumors, compared with infertile women who did not use fertility drugs (adjusted odds ratio, 0.64; Fertil Steril. 2013;99[7]:2031-6). There also was no increased risk because of underlying infertility or any increase in borderline tumors. More recently, an abstract presented at the annual meeting of the European Society of Human Reproduction and Embryology, based on a large cohort study from Denmark, found a slightly higher overall risk of ovarian cancer among the ART women (0.11%), compared with non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous (a risk factor for ovarian cancer) and in the ART women who had a female cause of infertility. In an analysis from Great Britain, increased ovarian tumor risk was limited to women with endometriosis, low parity, or both (BMJ. 2018;362:k2644). Dr. Gambone noted that an article published online Oct. 23, 2017 in Nature Communication implicates the fallopian tube, rather than the ovaries, as a probable source of papillary serous cancers.

Women who are subfertile should be counseled about the increased risk of birth defects, irrespective of whether they undergo IVF or not, said Dr. Gambone, who also runs a private infertility practice in Durango, Colo. Studies consistently show an increased risk associated with subfertility. A large, retrospective cohort analysis of live and stillbirths from 2004 to 2010 in Massachusetts found that congenital anomalies were reported in 2% of ART births, 1.7% of subfertile births, and 1.4% of fertile births (Birth Defects Res. 2017 Aug 15;109[14]:1144-53). The adjusted prevalence ratios for birth defects were 1.5 for ART births and 1.3 for subfertile births, compared with fertile mother births. The researchers observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects.

“The absolute risk of birth defects is small with ART,” Dr. Gambone said. “A significant portion [but not all] is related to multiple births and underlying subfertility.” A more recent analysis found that subfertile women were 21% more likely to have babies born with birth defects, compared with fertile women (Pediatrics. 2018 Jul; e20174069).

In a study of the overall risk and etiology of major birth defects, researchers from Utah determined that they affect 1 in 33 babies in the United States at an annual direct cost of $2.6 billion per year (BMJ. 2017;357:j2249). Although major birth defects are the leading cause of infant mortality (20%), a known cause of the defect was established in only 20.2% of cases. “Of that percentage, the majority are chromosome or genetic causes,” Dr. Gambone said. “Interestingly, ART and/or subfertility were not listed in this analysis as causes of birth defects. However, the authors speculated that as genetic technology improves, both genetic and epigenetic causes will be identified.”

Dr. Gambone reported no relevant financial disclosures.

[email protected]

Operative experience in open arterial vascular surgery procedures for general surgery residents has significantly declined, according to the results of a study of the Accreditation Council for Graduate Medical Education (ACGME) national case log reports, which lists the mean numbers of operations performed.

“Because fundamental vascular surgery skills are necessary for operative general surgery, vascular surgery should remain an essential content area. However, programs cannot solely depend on operative experience to teach fundamental vascular surgery skills,” John R. Potts III, MD, FACS, and R. James Valentine, MD, FACS, stated in their report published online in Annals of Surgery.

The number of individuals completing ACGME-accredited general surgery and vascular surgery training each year of the study was obtained from public reports of the ACGME as well as the available summary national data regarding the reported operative experience of residents completing general surgery programs.

The researchers found that over 15 years (academic year 2001-2002 through AY 2016-2017), the total vascular operations performed by general surgery residents significantly declined as did the total open arterial vascular procedures, including those in seven of nine categories (P less than .0001).

The issue of adequate exposure to vascular procedures for general surgery residents is complex. “The number of individuals completing general surgery residency annually has increased by approximately 20% since AY 2001-2. During the same period, the number of open arterial operations reported by general surgery residents decreased by approximately 38%. Thus, the declining experience is clearly not simply a matter of distributing the same number of operations to a larger number of individuals,” the investigators reported.

The ACGME-designated “essential content areas” have increased in recent years for general surgery trainees to now encompass alimentary tract, abdomen, breast, head and neck, endocrine system, the surgical management of trauma, soft tissues, pediatric surgery, surgical critical care, surgical oncology, and vascular surgery. The essential content areas compete to varying degrees for the trainee’s time, potentially cutting into not just vascular cases but other areas as well. It is also the case that general surgery trainees are often in an institutional setting where they are competing with vascular surgery residents for the same pool of vascular surgery patients.

During those last 5 years, significant declines occurred in five categories: aneurysm, cerebrovascular disease, arteriovenous dialysis access, peripheral vascular disease, and extra-anatomic bypass, according to the authors.

“Knowledge of arterial anatomy, approaches, control, and repair are crucial to the practice of operative general surgery. In the face of declining experience for their resident as surgeon in open arterial operations, general surgery programs must augment resident education in the principles of vascular surgery through other means,” the authors concluded.

Portions of this study were presented at the2018 meeting of the American Surgical Association.

Dr. Potts and Dr. Valentine reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Potts JR et al. Ann Surg. 2018 Jul 24. doi: 10.1097/SLA.0000000000002951.

Operative experience in open arterial vascular surgery procedures for general surgery residents has significantly declined, according to the results of a study of the Accreditation Council for Graduate Medical Education (ACGME) national case log reports, which lists the mean numbers of operations performed.

“Because fundamental vascular surgery skills are necessary for operative general surgery, vascular surgery should remain an essential content area. However, programs cannot solely depend on operative experience to teach fundamental vascular surgery skills,” John R. Potts III, MD, FACS, and R. James Valentine, MD, FACS, stated in their report published online in Annals of Surgery.

The number of individuals completing ACGME-accredited general surgery and vascular surgery training each year of the study was obtained from public reports of the ACGME as well as the available summary national data regarding the reported operative experience of residents completing general surgery programs.

The researchers found that over 15 years (academic year 2001-2002 through AY 2016-2017), the total vascular operations performed by general surgery residents significantly declined as did the total open arterial vascular procedures, including those in seven of nine categories (P less than .0001).

The issue of adequate exposure to vascular procedures for general surgery residents is complex. “The number of individuals completing general surgery residency annually has increased by approximately 20% since AY 2001-2. During the same period, the number of open arterial operations reported by general surgery residents decreased by approximately 38%. Thus, the declining experience is clearly not simply a matter of distributing the same number of operations to a larger number of individuals,” the investigators reported.

The ACGME-designated “essential content areas” have increased in recent years for general surgery trainees to now encompass alimentary tract, abdomen, breast, head and neck, endocrine system, the surgical management of trauma, soft tissues, pediatric surgery, surgical critical care, surgical oncology, and vascular surgery. The essential content areas compete to varying degrees for the trainee’s time, potentially cutting into not just vascular cases but other areas as well. It is also the case that general surgery trainees are often in an institutional setting where they are competing with vascular surgery residents for the same pool of vascular surgery patients.

During those last 5 years, significant declines occurred in five categories: aneurysm, cerebrovascular disease, arteriovenous dialysis access, peripheral vascular disease, and extra-anatomic bypass, according to the authors.

“Knowledge of arterial anatomy, approaches, control, and repair are crucial to the practice of operative general surgery. In the face of declining experience for their resident as surgeon in open arterial operations, general surgery programs must augment resident education in the principles of vascular surgery through other means,” the authors concluded.

Portions of this study were presented at the2018 meeting of the American Surgical Association.

Dr. Potts and Dr. Valentine reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Potts JR et al. Ann Surg. 2018 Jul 24. doi: 10.1097/SLA.0000000000002951.

Operative experience in open arterial vascular surgery procedures for general surgery residents has significantly declined, according to the results of a study of the Accreditation Council for Graduate Medical Education (ACGME) national case log reports, which lists the mean numbers of operations performed.

“Because fundamental vascular surgery skills are necessary for operative general surgery, vascular surgery should remain an essential content area. However, programs cannot solely depend on operative experience to teach fundamental vascular surgery skills,” John R. Potts III, MD, FACS, and R. James Valentine, MD, FACS, stated in their report published online in Annals of Surgery.

The number of individuals completing ACGME-accredited general surgery and vascular surgery training each year of the study was obtained from public reports of the ACGME as well as the available summary national data regarding the reported operative experience of residents completing general surgery programs.

The researchers found that over 15 years (academic year 2001-2002 through AY 2016-2017), the total vascular operations performed by general surgery residents significantly declined as did the total open arterial vascular procedures, including those in seven of nine categories (P less than .0001).

The issue of adequate exposure to vascular procedures for general surgery residents is complex. “The number of individuals completing general surgery residency annually has increased by approximately 20% since AY 2001-2. During the same period, the number of open arterial operations reported by general surgery residents decreased by approximately 38%. Thus, the declining experience is clearly not simply a matter of distributing the same number of operations to a larger number of individuals,” the investigators reported.

The ACGME-designated “essential content areas” have increased in recent years for general surgery trainees to now encompass alimentary tract, abdomen, breast, head and neck, endocrine system, the surgical management of trauma, soft tissues, pediatric surgery, surgical critical care, surgical oncology, and vascular surgery. The essential content areas compete to varying degrees for the trainee’s time, potentially cutting into not just vascular cases but other areas as well. It is also the case that general surgery trainees are often in an institutional setting where they are competing with vascular surgery residents for the same pool of vascular surgery patients.

During those last 5 years, significant declines occurred in five categories: aneurysm, cerebrovascular disease, arteriovenous dialysis access, peripheral vascular disease, and extra-anatomic bypass, according to the authors.

“Knowledge of arterial anatomy, approaches, control, and repair are crucial to the practice of operative general surgery. In the face of declining experience for their resident as surgeon in open arterial operations, general surgery programs must augment resident education in the principles of vascular surgery through other means,” the authors concluded.

Portions of this study were presented at the2018 meeting of the American Surgical Association.

Dr. Potts and Dr. Valentine reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Potts JR et al. Ann Surg. 2018 Jul 24. doi: 10.1097/SLA.0000000000002951.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

An individual prescribing plan based on inpatient use for women who delivered by cesarean section was associated with a lower number of unused oxycodone tablets, according to research published in Obstetrics & Gynecology.

BackyardProduction/Thinkstock

In a second study, there was a significantly lower number of opioid tablets prescribed for women who delivered by cesarean section after a shared decision-making quality improvement plan was implemented on an inpatient basis.

Sarah S. Osmundson, MD, MS, of Vanderbilt University Medical Center in Nashville, Tenn., and her colleagues conducted a randomized, controlled trial of women who underwent cesarean delivery between June and August 2017. Of these women, 85 were randomized to receive standard care of 30 oxycodone tablets (5 mg) and 87 received an individualized care plan based on inpatient use of oxycodone. Patients were a minimum of 18 years old with similar baseline characteristics and inpatient pain scores.

The investigators found that women who were randomized to the individual care group received 14 oxycodone tablets (interquartile range, 12-16) and had 5 tablets (IQR, 1-8) left 2 weeks after discharge, compared with women who were prescribed 30 tablets in the standard care group (IQR, 30-30; P less than .001) and left 10 tablets unused (IQR, 0-22; P less than .001). There were no significant differences regarding patient-reported pain outcomes in either group, and women used about half as many prescribed tablets in the individualized group (8; IQR, 4-14), compared with women in the standard care group (15; IQR, 6-30; P less than .001).

Most women reported that they used opioids to treat pain and 30% said they believed they were supposed to finish all the tablets that were prescribed, the researchers noted. There were 11 patients (13%) in the standard care group and 12 (14%) in the individualized group who did not use any opioids; similarly, 23 patients (27%) in the standard care group and 21 (24%) in the individual care group used all tablets prescribed.

“If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups,” Dr. Osmundson and her colleagues wrote. “These findings suggest that factors other than pain influence opioid use patterns.”

In a second study, Malavika Prabhu, MD, of Massachusetts General Hospital in Boston, and her colleagues employed a prospective quality improvement (QI) initiative for women prescribed opioids after cesarean delivery. They evaluated the opioid use of 624 women and counseled them at discharge on the need for prescription opioids, using shared decision-making to determine the number of opioid tablets, with a maximum number of 30 oxycodone tablets (5 mg). The investigators also changed their protocol for multimodal analgesia to scheduled acetaminophen and NSAIDs. Patients were a mean of 30 years old and more than 50% were white. Median gestational age was 39 weeks at delivery. In a second phase of the study, the investigators lowered the maximum number of opioid tablets prescribed to 25 tablets.

At discharge, the mean number of prescribed opioid tablets decreased to 27 tablets from 33 tablets in phase 1 (P less than .01). In phase 2, the number of tablets further decreased to 22 tablets from 25 tablets (P less than .01). The investigators noted no significant difference in the refill rate during phase 1 (8% vs. 9%; P less than .79) and phase 2 (6% vs. 6%; P = .72). There was a significant increase in prescribing of acetaminophen from 33% at baseline to 77% at the end of phase 1 and an increase at the beginning of phase 2 at 91% to 92% at the end of phase 2. There were no statistically significant differences among prescriptions of ibuprofen at any phase time point.

“As a result of our success in decreasing opioid prescribing after cesarean delivery, our current protocol has again been amended to recommend a maximum of 20 tablets of 5-mg oxycodone (or equivalent opioid) prescribed at the time of discharge,” Dr. Prabhu and her colleagues wrote. “This decrease, which represents a 50% decrease in the departmental standard before this study, has been successfully implemented in 18 months. In addition, efforts to optimize multimodal analgesic use continue both inpatient and on discharge.”

Dr. Osmundson was supported by a grant from the National Institutes of Health, and the research also was supported by an award from the National Center for Advancing Translational Sciences; the authors of the study reported no relevant conflicts of interest. The authors led by Dr. Prabhu had no relevant financial disclosures.
 

SOURCE: Prabhu M et al. Obstet Gyncol. 2018 Aug 4; doi: 10.1097/AOG.0000000000002789, and Osmundson SS et al. Obstet Gynecol. 2018 Aug 6; doi: 10.1097/AOG.0000000000002782.

For close to 6 decades, since the approval of imipramine in 1959, all Food and Drug Administration-approved medications for depression worked through the monoamine system, in some ways altering the concentration of serotonin, norepinephrine, or dopamine within synapses or binding to post synaptic receptors. A conservative estimate has at least a third of patients with depression not adequately responsive to these monoaminergic medications.

A host of medications in various stages of development might each offer unique additions to the current therapeutic paradigm. Compounds closest to market include N-methyl-D-aspartate (NMDA) blockers such as esketamine or rapastinel; opioid receptor partial agonists and antagonists, such as Alkermes 5461; and a GABA_A receptor modulator, brexanolone. A further off, more speculative intervention involves the use of psychedelic drugs like psilocybin.

NMDA antagonists have gained the highest visibility after some promising results in early studies looking at intravenous ketamine, an anesthetic agent approved by the FDA in 1970 for treatment-resistant depression. This has led to several companies trying to develop a patentable NMDA antagonist for depression. The most likely first candidate is one of the enantiomers of ketamine, esketamine, which, because of higher binding affinity, can be dosed intranasally rather than intravenously. Studies are completed to establish efficacy in TRD² [treatment-resistant depression] as well as acute suicidality³. Johnson & Johnson plans to submit these results for FDA approval this year.

Another promising NMDA antagonist, rapastinel, is wending its way through clinical trials – but should it be approved, its use might be limited by the requirement for intravenous delivery.

Despite only early evidence for efficacy in depression, the easy availability of ketamine for infusion has created a cadre of independent clinicians as well as some academic clinics offering intravenous ketamine infusions for those with difficult-to-treat depression and adequate finances to pay for off-label treatment (some insurance companies as well have supported its use). It is understandable to try to offer patients suffering with refractory illnesses anything the field has to offer, but the limitations on our knowledge, especially about the efficacy and safety of long-term use of ketamine for depression, need to be taken into account⁴. There is little to no regulation around providing intravenous ketamine, and clinicians and patients should be aware of the risks, take care in the administration of the drug, and watch for the potential of dissociation or substance abuse along with being clear about the likelihood of benefit being at best around 50%. As more evidence and experience are collected, NMDA antagonists might offer a unique efficacy profile within safe boundaries.

Opioid agonists have some antidepressant activity, but tolerance to it quickly develops – requiring users to take increasingly higher doses. Would a partial opioid agonist coupled with a pure opioid antagonist provide ongoing efficacy at a continuous dose with adequate safety? A combination medication containing buprenorphine, a partial* mu- and kappa-opioid partial agonist, and samidorphan, a mu-opioid antagonist, is currently being reviewed by the FDA. The phase 3 studies are not yet published. However, the phase 2 published trial demonstrated efficacy at low doses (2 mg of buprenorphine with 2 mg of samidorphan) as an adjunctive medication in treatment-resistant depression⁵. While offering a novel mechanism of action and a reasonable safety profile seen in several poster presentations, though not published articles, the drug – should it receive approval – will require an intensive effort to educate practitioners and the public about the critical differences (especially with regard to risk/benefits of long-term use, abuse potential, and safety) between opiate agonism and opiate modulation/antagonism.

Brexanolone, an intravenous formulation of allopregnanolone, a positive allosteric modulator of gamma-aminobutyric acid (GABA_A) receptors, has been studied for the treatment of postpartum depression⁶. Early development has focused on an intravenous delivery system and a unique target population of postpartum depression, but the novel concept of targeting GABA_A receptors might prove fruitful with a wider population of depressed patients with inadequate responses to existing antidepressants. An oral formulation, SAGE-217, is in early clinical trials.

While much earlier in the development for FDA approval, psychedelics, particularly psilocybin, have been investigated for use in treatment-resistant depression. A small double-blind trial in terminal cancer patients showed that psilocybin had a remarkable palliative effect on depression and anxiety⁷. An open label study of treatment-resistant depressed patients demonstrated lasting benefit over 6 months after two doses of psilocybin⁸. A neuroimaging study supported the idea that changes in resting state functional connectivity in specific brain regions from exposure to psilocybin might account for alleviation in depressive symptoms⁹. These findings are preliminary, but they have sparked the commencement of a few phase 2 randomized trials for psychedelic drugs. It should be noted that all these trial to date – and those planned – require dosing to be done in a very controlled and supervised psychologically supportive environment.

Which of these treatments will make it to market? That remains unclear, but it is reassuring that so many different novel paradigms for addressing treatment-resistant depression are in development.
 

Dr. Aaronson is the director of clinical research programs at the Sheppard Pratt Health System in Baltimore. He serves as a consultant to several companies, including Alkermes, Genomind, LivaNova, Neuronetics, and Sage Therapeutics. He has received honoraria for speaking from Neurocrine, Otsuka, and Sunovion. He has received research support from Neuronetics. Dr. Aaronson also serves as a clinical associate professor of psychiatry at the University of Maryland, Baltimore, and is a Distinguished Fellow of the American Psychiatric Association and a Fellow of the American College of Psychiatrists.
 

References

1. Am J Psychiatry. 2006;163(11):1905-17.

2. JAMA Psychiatry. 2018 Feb 1;75(2):139-48.

3. Am J Psychiatry. 2018 Jul 1;175(7):620-30.

4. JAMA Psychiatry. 2017;74(4):399-405.

5. Am J Psychiatry. 2016 May 1;173(5):499-508.

6. Lancet. 2017 Jul 29;390(10093):480-9.

7. J Psychopharmacol. 2016;30(12):1181-97.

8. Psychopharmacology (Berl). 2018 Feb;235(2):399-408.

9. Sci Rep. 2017 Oct 13;7(1):13187.

*Correction, 10/18/2019: An earlier version of this story misidentified buprenorphine.

For close to 6 decades, since the approval of imipramine in 1959, all Food and Drug Administration-approved medications for depression worked through the monoamine system, in some ways altering the concentration of serotonin, norepinephrine, or dopamine within synapses or binding to post synaptic receptors. A conservative estimate has at least a third of patients with depression not adequately responsive to these monoaminergic medications.

A host of medications in various stages of development might each offer unique additions to the current therapeutic paradigm. Compounds closest to market include N-methyl-D-aspartate (NMDA) blockers such as esketamine or rapastinel; opioid receptor partial agonists and antagonists, such as Alkermes 5461; and a GABA_A receptor modulator, brexanolone. A further off, more speculative intervention involves the use of psychedelic drugs like psilocybin.

NMDA antagonists have gained the highest visibility after some promising results in early studies looking at intravenous ketamine, an anesthetic agent approved by the FDA in 1970 for treatment-resistant depression. This has led to several companies trying to develop a patentable NMDA antagonist for depression. The most likely first candidate is one of the enantiomers of ketamine, esketamine, which, because of higher binding affinity, can be dosed intranasally rather than intravenously. Studies are completed to establish efficacy in TRD² [treatment-resistant depression] as well as acute suicidality³. Johnson & Johnson plans to submit these results for FDA approval this year.

Another promising NMDA antagonist, rapastinel, is wending its way through clinical trials – but should it be approved, its use might be limited by the requirement for intravenous delivery.

Despite only early evidence for efficacy in depression, the easy availability of ketamine for infusion has created a cadre of independent clinicians as well as some academic clinics offering intravenous ketamine infusions for those with difficult-to-treat depression and adequate finances to pay for off-label treatment (some insurance companies as well have supported its use). It is understandable to try to offer patients suffering with refractory illnesses anything the field has to offer, but the limitations on our knowledge, especially about the efficacy and safety of long-term use of ketamine for depression, need to be taken into account⁴. There is little to no regulation around providing intravenous ketamine, and clinicians and patients should be aware of the risks, take care in the administration of the drug, and watch for the potential of dissociation or substance abuse along with being clear about the likelihood of benefit being at best around 50%. As more evidence and experience are collected, NMDA antagonists might offer a unique efficacy profile within safe boundaries.

Opioid agonists have some antidepressant activity, but tolerance to it quickly develops – requiring users to take increasingly higher doses. Would a partial opioid agonist coupled with a pure opioid antagonist provide ongoing efficacy at a continuous dose with adequate safety? A combination medication containing buprenorphine, a partial* mu- and kappa-opioid partial agonist, and samidorphan, a mu-opioid antagonist, is currently being reviewed by the FDA. The phase 3 studies are not yet published. However, the phase 2 published trial demonstrated efficacy at low doses (2 mg of buprenorphine with 2 mg of samidorphan) as an adjunctive medication in treatment-resistant depression⁵. While offering a novel mechanism of action and a reasonable safety profile seen in several poster presentations, though not published articles, the drug – should it receive approval – will require an intensive effort to educate practitioners and the public about the critical differences (especially with regard to risk/benefits of long-term use, abuse potential, and safety) between opiate agonism and opiate modulation/antagonism.

Brexanolone, an intravenous formulation of allopregnanolone, a positive allosteric modulator of gamma-aminobutyric acid (GABA_A) receptors, has been studied for the treatment of postpartum depression⁶. Early development has focused on an intravenous delivery system and a unique target population of postpartum depression, but the novel concept of targeting GABA_A receptors might prove fruitful with a wider population of depressed patients with inadequate responses to existing antidepressants. An oral formulation, SAGE-217, is in early clinical trials.

While much earlier in the development for FDA approval, psychedelics, particularly psilocybin, have been investigated for use in treatment-resistant depression. A small double-blind trial in terminal cancer patients showed that psilocybin had a remarkable palliative effect on depression and anxiety⁷. An open label study of treatment-resistant depressed patients demonstrated lasting benefit over 6 months after two doses of psilocybin⁸. A neuroimaging study supported the idea that changes in resting state functional connectivity in specific brain regions from exposure to psilocybin might account for alleviation in depressive symptoms⁹. These findings are preliminary, but they have sparked the commencement of a few phase 2 randomized trials for psychedelic drugs. It should be noted that all these trial to date – and those planned – require dosing to be done in a very controlled and supervised psychologically supportive environment.

Which of these treatments will make it to market? That remains unclear, but it is reassuring that so many different novel paradigms for addressing treatment-resistant depression are in development.
 

Dr. Aaronson is the director of clinical research programs at the Sheppard Pratt Health System in Baltimore. He serves as a consultant to several companies, including Alkermes, Genomind, LivaNova, Neuronetics, and Sage Therapeutics. He has received honoraria for speaking from Neurocrine, Otsuka, and Sunovion. He has received research support from Neuronetics. Dr. Aaronson also serves as a clinical associate professor of psychiatry at the University of Maryland, Baltimore, and is a Distinguished Fellow of the American Psychiatric Association and a Fellow of the American College of Psychiatrists.
 

References

1. Am J Psychiatry. 2006;163(11):1905-17.

2. JAMA Psychiatry. 2018 Feb 1;75(2):139-48.

3. Am J Psychiatry. 2018 Jul 1;175(7):620-30.

4. JAMA Psychiatry. 2017;74(4):399-405.

5. Am J Psychiatry. 2016 May 1;173(5):499-508.

6. Lancet. 2017 Jul 29;390(10093):480-9.

7. J Psychopharmacol. 2016;30(12):1181-97.

8. Psychopharmacology (Berl). 2018 Feb;235(2):399-408.

9. Sci Rep. 2017 Oct 13;7(1):13187.

*Correction, 10/18/2019: An earlier version of this story misidentified buprenorphine.

For close to 6 decades, since the approval of imipramine in 1959, all Food and Drug Administration-approved medications for depression worked through the monoamine system, in some ways altering the concentration of serotonin, norepinephrine, or dopamine within synapses or binding to post synaptic receptors. A conservative estimate has at least a third of patients with depression not adequately responsive to these monoaminergic medications.

A host of medications in various stages of development might each offer unique additions to the current therapeutic paradigm. Compounds closest to market include N-methyl-D-aspartate (NMDA) blockers such as esketamine or rapastinel; opioid receptor partial agonists and antagonists, such as Alkermes 5461; and a GABA_A receptor modulator, brexanolone. A further off, more speculative intervention involves the use of psychedelic drugs like psilocybin.

NMDA antagonists have gained the highest visibility after some promising results in early studies looking at intravenous ketamine, an anesthetic agent approved by the FDA in 1970 for treatment-resistant depression. This has led to several companies trying to develop a patentable NMDA antagonist for depression. The most likely first candidate is one of the enantiomers of ketamine, esketamine, which, because of higher binding affinity, can be dosed intranasally rather than intravenously. Studies are completed to establish efficacy in TRD² [treatment-resistant depression] as well as acute suicidality³. Johnson & Johnson plans to submit these results for FDA approval this year.

Another promising NMDA antagonist, rapastinel, is wending its way through clinical trials – but should it be approved, its use might be limited by the requirement for intravenous delivery.

Despite only early evidence for efficacy in depression, the easy availability of ketamine for infusion has created a cadre of independent clinicians as well as some academic clinics offering intravenous ketamine infusions for those with difficult-to-treat depression and adequate finances to pay for off-label treatment (some insurance companies as well have supported its use). It is understandable to try to offer patients suffering with refractory illnesses anything the field has to offer, but the limitations on our knowledge, especially about the efficacy and safety of long-term use of ketamine for depression, need to be taken into account⁴. There is little to no regulation around providing intravenous ketamine, and clinicians and patients should be aware of the risks, take care in the administration of the drug, and watch for the potential of dissociation or substance abuse along with being clear about the likelihood of benefit being at best around 50%. As more evidence and experience are collected, NMDA antagonists might offer a unique efficacy profile within safe boundaries.

Opioid agonists have some antidepressant activity, but tolerance to it quickly develops – requiring users to take increasingly higher doses. Would a partial opioid agonist coupled with a pure opioid antagonist provide ongoing efficacy at a continuous dose with adequate safety? A combination medication containing buprenorphine, a partial* mu- and kappa-opioid partial agonist, and samidorphan, a mu-opioid antagonist, is currently being reviewed by the FDA. The phase 3 studies are not yet published. However, the phase 2 published trial demonstrated efficacy at low doses (2 mg of buprenorphine with 2 mg of samidorphan) as an adjunctive medication in treatment-resistant depression⁵. While offering a novel mechanism of action and a reasonable safety profile seen in several poster presentations, though not published articles, the drug – should it receive approval – will require an intensive effort to educate practitioners and the public about the critical differences (especially with regard to risk/benefits of long-term use, abuse potential, and safety) between opiate agonism and opiate modulation/antagonism.

Brexanolone, an intravenous formulation of allopregnanolone, a positive allosteric modulator of gamma-aminobutyric acid (GABA_A) receptors, has been studied for the treatment of postpartum depression⁶. Early development has focused on an intravenous delivery system and a unique target population of postpartum depression, but the novel concept of targeting GABA_A receptors might prove fruitful with a wider population of depressed patients with inadequate responses to existing antidepressants. An oral formulation, SAGE-217, is in early clinical trials.

While much earlier in the development for FDA approval, psychedelics, particularly psilocybin, have been investigated for use in treatment-resistant depression. A small double-blind trial in terminal cancer patients showed that psilocybin had a remarkable palliative effect on depression and anxiety⁷. An open label study of treatment-resistant depressed patients demonstrated lasting benefit over 6 months after two doses of psilocybin⁸. A neuroimaging study supported the idea that changes in resting state functional connectivity in specific brain regions from exposure to psilocybin might account for alleviation in depressive symptoms⁹. These findings are preliminary, but they have sparked the commencement of a few phase 2 randomized trials for psychedelic drugs. It should be noted that all these trial to date – and those planned – require dosing to be done in a very controlled and supervised psychologically supportive environment.

Which of these treatments will make it to market? That remains unclear, but it is reassuring that so many different novel paradigms for addressing treatment-resistant depression are in development.
 

Dr. Aaronson is the director of clinical research programs at the Sheppard Pratt Health System in Baltimore. He serves as a consultant to several companies, including Alkermes, Genomind, LivaNova, Neuronetics, and Sage Therapeutics. He has received honoraria for speaking from Neurocrine, Otsuka, and Sunovion. He has received research support from Neuronetics. Dr. Aaronson also serves as a clinical associate professor of psychiatry at the University of Maryland, Baltimore, and is a Distinguished Fellow of the American Psychiatric Association and a Fellow of the American College of Psychiatrists.
 

References

1. Am J Psychiatry. 2006;163(11):1905-17.

2. JAMA Psychiatry. 2018 Feb 1;75(2):139-48.

3. Am J Psychiatry. 2018 Jul 1;175(7):620-30.

4. JAMA Psychiatry. 2017;74(4):399-405.

5. Am J Psychiatry. 2016 May 1;173(5):499-508.

6. Lancet. 2017 Jul 29;390(10093):480-9.

7. J Psychopharmacol. 2016;30(12):1181-97.

8. Psychopharmacology (Berl). 2018 Feb;235(2):399-408.

9. Sci Rep. 2017 Oct 13;7(1):13187.

*Correction, 10/18/2019: An earlier version of this story misidentified buprenorphine.

Let’s start with an exercise, shall we? What was the last vacation you went on? How would you rate that vacation on a scale of 1-10?

How you came up with that score is likely not entirely reflective of your actual experience. Understanding how we remember experiences is critical for the work we do everyday. Health care is the ultimate service industry and understanding patients’ experiences will give you a significant advantage in your practice.

My last vacation was in Alaska. I’d rate it a 9 out of 10. How did I come up with that score? It is not the mean score of the entire trip as you might expect. Rather, I took a shortcut and thought only about the highlights to come up with a number. We remember, and evaluate, our experiences as a series of discrete events. In considering these events, it is only the highs, the lows, and the transitions that matter. Think about the score you gave your vacation. What specific moments did you remember?

This phenomenon is not specific to vacations. It applies to all service experiences. When your patients evaluate you, they will ignore most of what occurred and focus on only a few moments. Fair or not, it is from these bits only that they will rate their entire experience. This information helps us devise strategies to achieve high satisfaction scores: Focus on the high points, address the low points, if any, and be sure the transitions are pleasant.

For example, a patient might come to see you for a procedure. It could be something positive, such as injection of cosmetic filler or something negative like a colonoscopy. Either way, being finished with the procedure will likely be the best part for them. Don’t rush this time; instead of quickly moving on, take a moment to acknowledge you’re done, how well the patient did, or how much better they will now look or feel. Engaging with your patient at this moment can improve the salience of their experience and increase the likelihood that she or he will remember the appointment favorably and rate you accordingly, if given the opportunity.

In the same way, if you are aware your patient has experienced something negative, try to respond to it right away. Acknowledge if she or he expressed frustration, such as a long wait or pain, then take a minute to address or reframe it. Blunting the severity of the service failure can blunt their recall of it. This will make it less likely that it becomes a memorable part of their experience.

Last, transitions matter. These are the moments when your patient shifts from one setting to another, such as arriving at your office, moving from the waiting room to the exam room, and wrapping up the visit with the receptionist. Many of these moments will be managed by your staff. Therefore, invest time reminding them of their importance and teaching them tips and techniques to help patients transition smoothly and to feel well cared for. There will likely be a wonderful return on investment for them, you and, most importantly, your patients.


 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Let’s start with an exercise, shall we? What was the last vacation you went on? How would you rate that vacation on a scale of 1-10?

How you came up with that score is likely not entirely reflective of your actual experience. Understanding how we remember experiences is critical for the work we do everyday. Health care is the ultimate service industry and understanding patients’ experiences will give you a significant advantage in your practice.

My last vacation was in Alaska. I’d rate it a 9 out of 10. How did I come up with that score? It is not the mean score of the entire trip as you might expect. Rather, I took a shortcut and thought only about the highlights to come up with a number. We remember, and evaluate, our experiences as a series of discrete events. In considering these events, it is only the highs, the lows, and the transitions that matter. Think about the score you gave your vacation. What specific moments did you remember?

This phenomenon is not specific to vacations. It applies to all service experiences. When your patients evaluate you, they will ignore most of what occurred and focus on only a few moments. Fair or not, it is from these bits only that they will rate their entire experience. This information helps us devise strategies to achieve high satisfaction scores: Focus on the high points, address the low points, if any, and be sure the transitions are pleasant.

For example, a patient might come to see you for a procedure. It could be something positive, such as injection of cosmetic filler or something negative like a colonoscopy. Either way, being finished with the procedure will likely be the best part for them. Don’t rush this time; instead of quickly moving on, take a moment to acknowledge you’re done, how well the patient did, or how much better they will now look or feel. Engaging with your patient at this moment can improve the salience of their experience and increase the likelihood that she or he will remember the appointment favorably and rate you accordingly, if given the opportunity.

In the same way, if you are aware your patient has experienced something negative, try to respond to it right away. Acknowledge if she or he expressed frustration, such as a long wait or pain, then take a minute to address or reframe it. Blunting the severity of the service failure can blunt their recall of it. This will make it less likely that it becomes a memorable part of their experience.

Last, transitions matter. These are the moments when your patient shifts from one setting to another, such as arriving at your office, moving from the waiting room to the exam room, and wrapping up the visit with the receptionist. Many of these moments will be managed by your staff. Therefore, invest time reminding them of their importance and teaching them tips and techniques to help patients transition smoothly and to feel well cared for. There will likely be a wonderful return on investment for them, you and, most importantly, your patients.


 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Let’s start with an exercise, shall we? What was the last vacation you went on? How would you rate that vacation on a scale of 1-10?

How you came up with that score is likely not entirely reflective of your actual experience. Understanding how we remember experiences is critical for the work we do everyday. Health care is the ultimate service industry and understanding patients’ experiences will give you a significant advantage in your practice.

My last vacation was in Alaska. I’d rate it a 9 out of 10. How did I come up with that score? It is not the mean score of the entire trip as you might expect. Rather, I took a shortcut and thought only about the highlights to come up with a number. We remember, and evaluate, our experiences as a series of discrete events. In considering these events, it is only the highs, the lows, and the transitions that matter. Think about the score you gave your vacation. What specific moments did you remember?

This phenomenon is not specific to vacations. It applies to all service experiences. When your patients evaluate you, they will ignore most of what occurred and focus on only a few moments. Fair or not, it is from these bits only that they will rate their entire experience. This information helps us devise strategies to achieve high satisfaction scores: Focus on the high points, address the low points, if any, and be sure the transitions are pleasant.

For example, a patient might come to see you for a procedure. It could be something positive, such as injection of cosmetic filler or something negative like a colonoscopy. Either way, being finished with the procedure will likely be the best part for them. Don’t rush this time; instead of quickly moving on, take a moment to acknowledge you’re done, how well the patient did, or how much better they will now look or feel. Engaging with your patient at this moment can improve the salience of their experience and increase the likelihood that she or he will remember the appointment favorably and rate you accordingly, if given the opportunity.

In the same way, if you are aware your patient has experienced something negative, try to respond to it right away. Acknowledge if she or he expressed frustration, such as a long wait or pain, then take a minute to address or reframe it. Blunting the severity of the service failure can blunt their recall of it. This will make it less likely that it becomes a memorable part of their experience.

Last, transitions matter. These are the moments when your patient shifts from one setting to another, such as arriving at your office, moving from the waiting room to the exam room, and wrapping up the visit with the receptionist. Many of these moments will be managed by your staff. Therefore, invest time reminding them of their importance and teaching them tips and techniques to help patients transition smoothly and to feel well cared for. There will likely be a wonderful return on investment for them, you and, most importantly, your patients.


 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Acute aortic occlusion (AAO) is a relatively rare vascular emergency. The actual incidence of AAO is unknown but has been variously reported to be 1% to 4%, and the incidence of AAO secondary to infrarenal abdominal aortic aneurysm is reported to be about 2%.¹ Acute aortic occlusion may present with acute onset of neurologic deficits as a consequence of spinal cord ischemia from thrombotic or embolic etiology. Risk factors for thrombosis include hypertension, tobacco smoking, and diabetes mellitus; heart disease and female gender are associated with embolism.² Spinal cord infarction accounts for only 1% to 2% of all strokes and is characterized by acute onset of paralysis, bowel and bladder dysfunction, and loss of pain and temperature perception. Proprioception and vibratory sense are typically preserved.³ The authors present the case of a patient with acute onset of lower limb paralysis and urinary incontinence who was later found to have AAO due to thrombosis and consequent spinal cord infarction.

Case Presentation

An 80-year-old white woman presented to the emergency department of Jefferson Regional Medical Center in Pine Bluff, Arkansas, with the sudden onset of severe lower back pain, bilateral leg paralysis and paresthesia, and urinary incontinence. The patient stated that she had been watching television when her legs began to tingle and feel numb. Within 10 to 20 minutes she was unable to move her legs and became incontinent of urine. She reported no injury or previous history of back pain. Her medical history was significant for “irregular heartbeat my whole life,” hypertension, hyperlipidemia, and bladder cancer. She was not receiving systemic anticoagulation therapy. She reported a previous 15 pack-year smoking history but reported that she had quit cigarette smoking and usually drank 1 glass of wine daily. She had previously completed 3 rounds of chemotherapy for bladder cancer and received her first radiation treatment earlier that day. The symptoms began about 8 hours later that evening.

On examination the patient was noted to be in acute distress due to pain. Her vital signs in triage were blood pressure (BP) 122/71 mm Hg, pulse 54 beats per min (BPM), respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 90% on 2 L/min oxygen via nasal cannula. Laboratory evaluation was remarkable only for serum sodium 132 mEq/L, potassium 2.8 mEq/L, and thrombocytosis with platelets 697 × 10³/μL. A neurologic examination showed normal motor function, strength of the upper extremities, and paralysis of the lower extremities, which were insensate to blunt or sharp touch and with decreased skin temperature from the groin distally. Pedal pulses were absent bilaterally. She was incontinent of urine and had anal sphincter laxity.

Magnetic resonance imaging showed bulging lumbar intervertebral discs and foraminal narrowing, which the consulting neurosurgeon did not feel explained her presentation and suggested that a vascular etiology was more likely. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis showed occlusion of the infrarenal abdominal aorta, bilateral common, and external iliac arteries. The proximal inferior mesenteric artery was occluded, and there was 90% stenosis of the proximal superior mesenteric artery with noncalcified plaque. There was no abdominal aortic aneurysm or dissection demonstrated. A chest CT was unremarkable.

The patient was started on IV heparin 800 U/h and transferred via ambulance to the University of Arkansas for Medical Sciences in Little Rock, Arkansas, for vascular surgery. On arrival her vital signs were BP 108/69 mm Hg, pulse 123 BPM, respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 94% on 2 L/min oxygen via nasal cannula. The patient’s electrocardiogram demonstrated atrial fibrillation with rapid ventricular response with premature ventricular complexes. On examination the bilateral lower extremities were cyanotic and cold to the touch. The pedal pulses were nonpalpable, and decreased distal sensation with dense paralysis was noted. 

The patient was taken emergently to the operating room (OR) for left axillary bifemoral bypass. Severe atherosclerotic disease was noted at surgery. She was transferred to the surgical intensive care unit (SICU) for postoperative hemodynamic monitoring. Her clinical course became complicated by mesenteric ischemia from chronic superior mesenteric artery (SMA) occlusion. On postoperative day 2, she became progressively more hypotensive, and she was placed on vasopressin 0.04 U/min and amiodarone 0.5 mg/min infusions.

Bedside echocardiography showed diffuse ventricular hypokinesis and a left ventricular ejection fraction (LVEF) of about 30% but no mural thrombus. The patient developed altered mental status and respiratory distress, and her serum lactate increased to 6.1 mg/dL. She was emergently intubated and taken to the OR to attempt recanalization of the SMA occlusion, which was unsuccessful. She was returned to the SICU for continued resuscitation and monitoring. She continued to decline with hypotensive pressures, increasing serum creatinine and lactate, and worsening metabolic acidosis. Management options and goals of care were discussed with the family, and it was decided to honor her do not resuscitate status and pursue comfort care. She was extubated and expired a short time after this was done.

Discussion

Acute aortic occlusion is a rare vascular emergency with a mortality rate that approaches 75%.^4-6 It results from numerous etiologies, including saddle embolism at the aortic bifurcation, acute thrombus formation, subsequent to aortic dissection, or other causes related to severe atherosclerotic disease or hypercoagulable states.^4,7

A recent retrospective series of 29 cases of AAO found that thrombosis was the cause for 76% of cases, and > 40% of patients had a hypercoagulable state either because of antiphospholipid antibody syndrome (17%) or malignancy (24%).⁶ The most common presentation of AAO is the abrupt onset of painful bilateral paresis or paraplegia.^5,6 While some studies have suggested that the major determinant of mortality is time elapsed until revascularization,⁷ other studies have reported that the neurologic status of the extremities is more closely related with mortality.²

The anterior spinal artery is the major independent provider of blood flow to the anterior two-thirds of the spinal cord, including the anterior horns, the anterior commissure, the anterior funiculi, and to a variable extent, the lateral funiculi. The largest segmental posterior radicular branch of the anterior spinal artery is the artery of Adamkiewicz, which arises from the T9 to T12 level on the left in 75% of cases and provides perfusion to the lumbar spinal cord and the conus medullaris. Obstruction of blood flow in this region has been implicated in the clinical picture of anterior cord syndrome characterized by abrupt onset of radicular pain, flaccid paresis or paralysis, sphincter dysfunction with urinary and fecal incontinence, and decreased pain and temperature sensation below a sensory level with spared proprioception and vibratory sensation.^{3, 8-10}

Aortography is the gold standard procedure for diagnosis of AAO, but it is a time-consuming procedure, and preoperative testing is controversial. Contrast-enhanced CT is useful for evaluation as it can be quickly accomplished and is more available in general hospitals. Moreover, CT scanning may reveal aortic dissections or aneurysms as the cause of occlusion. Deep Doppler ultrasonography also has demonstrated utility as a noninvasive and rapidly performed diagnostic procedure. Magnetic resonance angiography or CT should be performed for all cases unless the patient’s clinical condition prevents this evaluation. Imaging not only confirms diagnosis, but also is valuable for assessment and planning management.^11-14

Once the diagnosis of AAO is made, management with IV fluid hydration, heparin administration, and optimizing cardiac function are essential. However, conservative management with anticoagulation alone is associated with high mortality, and unless the ischemia is irreversible or unless the patient is in a dying state, surgery is appropriate.^5,7 Depending on the etiology of the AAO, anatomic considerations, and other patient factors, urgent revascularization with thrombo-embolectomy, direct aortic reconstruction, or anatomic or extra-anatomic bypass procedures may be employed. Aortic reconstruction has been advocated for all patients with infrarenal aortic occlusion given the concern for propagation of thrombosis at the distal aorta proximally to the renal and mesenteric arteries.⁷ Axillary-bifemoral bypass has been advocated as a rapid revascularization strategy with good patency and less physiologic strain for critically ill AAO patients.⁶

The patient in this study had a constellation of risk factors for developing AAO due to thrombosis and consequently sustaining spinal cord infarction. Echocardiography ruled out embolism of a mural thrombus. She had cardiac dysfunction due to atrial fibrillation and left ventricular failure causing a low-flow state (LVEF 30%). She also had a hypercoagulable state due to bladder malignancy in addition to severe atherosclerotic disease. She was not on systemic anticoagulation therapy because of her high fall risk. Hence, her risk for thrombosis was quite high. Despite expedient revascularization surgery, her postoperative course was complicated as a result of severe mesenteric ischemia due to chronic SMA occlusion, which caused her death.

Conclusion

Acute aortic occlusion is a rare vascular emergency. The patient presenting with the abrupt onset of bilateral leg pain, neurologic deficits of paresis/paralysis, sensory disturbance, and/or sphincter dysfunction, and stigmata of vascular compromise with lower extremity mottling should alert the physician to AAO. Acute aortic occlusion continues to have high morbidity and mortality, and prompt recognition and appropriate transfer for surgical intervention are essential for improving outcomes.

Acute aortic occlusion (AAO) is a relatively rare vascular emergency. The actual incidence of AAO is unknown but has been variously reported to be 1% to 4%, and the incidence of AAO secondary to infrarenal abdominal aortic aneurysm is reported to be about 2%.¹ Acute aortic occlusion may present with acute onset of neurologic deficits as a consequence of spinal cord ischemia from thrombotic or embolic etiology. Risk factors for thrombosis include hypertension, tobacco smoking, and diabetes mellitus; heart disease and female gender are associated with embolism.² Spinal cord infarction accounts for only 1% to 2% of all strokes and is characterized by acute onset of paralysis, bowel and bladder dysfunction, and loss of pain and temperature perception. Proprioception and vibratory sense are typically preserved.³ The authors present the case of a patient with acute onset of lower limb paralysis and urinary incontinence who was later found to have AAO due to thrombosis and consequent spinal cord infarction.

Case Presentation

An 80-year-old white woman presented to the emergency department of Jefferson Regional Medical Center in Pine Bluff, Arkansas, with the sudden onset of severe lower back pain, bilateral leg paralysis and paresthesia, and urinary incontinence. The patient stated that she had been watching television when her legs began to tingle and feel numb. Within 10 to 20 minutes she was unable to move her legs and became incontinent of urine. She reported no injury or previous history of back pain. Her medical history was significant for “irregular heartbeat my whole life,” hypertension, hyperlipidemia, and bladder cancer. She was not receiving systemic anticoagulation therapy. She reported a previous 15 pack-year smoking history but reported that she had quit cigarette smoking and usually drank 1 glass of wine daily. She had previously completed 3 rounds of chemotherapy for bladder cancer and received her first radiation treatment earlier that day. The symptoms began about 8 hours later that evening.

On examination the patient was noted to be in acute distress due to pain. Her vital signs in triage were blood pressure (BP) 122/71 mm Hg, pulse 54 beats per min (BPM), respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 90% on 2 L/min oxygen via nasal cannula. Laboratory evaluation was remarkable only for serum sodium 132 mEq/L, potassium 2.8 mEq/L, and thrombocytosis with platelets 697 × 10³/μL. A neurologic examination showed normal motor function, strength of the upper extremities, and paralysis of the lower extremities, which were insensate to blunt or sharp touch and with decreased skin temperature from the groin distally. Pedal pulses were absent bilaterally. She was incontinent of urine and had anal sphincter laxity.

Magnetic resonance imaging showed bulging lumbar intervertebral discs and foraminal narrowing, which the consulting neurosurgeon did not feel explained her presentation and suggested that a vascular etiology was more likely. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis showed occlusion of the infrarenal abdominal aorta, bilateral common, and external iliac arteries. The proximal inferior mesenteric artery was occluded, and there was 90% stenosis of the proximal superior mesenteric artery with noncalcified plaque. There was no abdominal aortic aneurysm or dissection demonstrated. A chest CT was unremarkable.

The patient was started on IV heparin 800 U/h and transferred via ambulance to the University of Arkansas for Medical Sciences in Little Rock, Arkansas, for vascular surgery. On arrival her vital signs were BP 108/69 mm Hg, pulse 123 BPM, respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 94% on 2 L/min oxygen via nasal cannula. The patient’s electrocardiogram demonstrated atrial fibrillation with rapid ventricular response with premature ventricular complexes. On examination the bilateral lower extremities were cyanotic and cold to the touch. The pedal pulses were nonpalpable, and decreased distal sensation with dense paralysis was noted. 

The patient was taken emergently to the operating room (OR) for left axillary bifemoral bypass. Severe atherosclerotic disease was noted at surgery. She was transferred to the surgical intensive care unit (SICU) for postoperative hemodynamic monitoring. Her clinical course became complicated by mesenteric ischemia from chronic superior mesenteric artery (SMA) occlusion. On postoperative day 2, she became progressively more hypotensive, and she was placed on vasopressin 0.04 U/min and amiodarone 0.5 mg/min infusions.

Bedside echocardiography showed diffuse ventricular hypokinesis and a left ventricular ejection fraction (LVEF) of about 30% but no mural thrombus. The patient developed altered mental status and respiratory distress, and her serum lactate increased to 6.1 mg/dL. She was emergently intubated and taken to the OR to attempt recanalization of the SMA occlusion, which was unsuccessful. She was returned to the SICU for continued resuscitation and monitoring. She continued to decline with hypotensive pressures, increasing serum creatinine and lactate, and worsening metabolic acidosis. Management options and goals of care were discussed with the family, and it was decided to honor her do not resuscitate status and pursue comfort care. She was extubated and expired a short time after this was done.

Discussion

Acute aortic occlusion is a rare vascular emergency with a mortality rate that approaches 75%.^4-6 It results from numerous etiologies, including saddle embolism at the aortic bifurcation, acute thrombus formation, subsequent to aortic dissection, or other causes related to severe atherosclerotic disease or hypercoagulable states.^4,7

A recent retrospective series of 29 cases of AAO found that thrombosis was the cause for 76% of cases, and > 40% of patients had a hypercoagulable state either because of antiphospholipid antibody syndrome (17%) or malignancy (24%).⁶ The most common presentation of AAO is the abrupt onset of painful bilateral paresis or paraplegia.^5,6 While some studies have suggested that the major determinant of mortality is time elapsed until revascularization,⁷ other studies have reported that the neurologic status of the extremities is more closely related with mortality.²

The anterior spinal artery is the major independent provider of blood flow to the anterior two-thirds of the spinal cord, including the anterior horns, the anterior commissure, the anterior funiculi, and to a variable extent, the lateral funiculi. The largest segmental posterior radicular branch of the anterior spinal artery is the artery of Adamkiewicz, which arises from the T9 to T12 level on the left in 75% of cases and provides perfusion to the lumbar spinal cord and the conus medullaris. Obstruction of blood flow in this region has been implicated in the clinical picture of anterior cord syndrome characterized by abrupt onset of radicular pain, flaccid paresis or paralysis, sphincter dysfunction with urinary and fecal incontinence, and decreased pain and temperature sensation below a sensory level with spared proprioception and vibratory sensation.^{3, 8-10}

Aortography is the gold standard procedure for diagnosis of AAO, but it is a time-consuming procedure, and preoperative testing is controversial. Contrast-enhanced CT is useful for evaluation as it can be quickly accomplished and is more available in general hospitals. Moreover, CT scanning may reveal aortic dissections or aneurysms as the cause of occlusion. Deep Doppler ultrasonography also has demonstrated utility as a noninvasive and rapidly performed diagnostic procedure. Magnetic resonance angiography or CT should be performed for all cases unless the patient’s clinical condition prevents this evaluation. Imaging not only confirms diagnosis, but also is valuable for assessment and planning management.^11-14

Once the diagnosis of AAO is made, management with IV fluid hydration, heparin administration, and optimizing cardiac function are essential. However, conservative management with anticoagulation alone is associated with high mortality, and unless the ischemia is irreversible or unless the patient is in a dying state, surgery is appropriate.^5,7 Depending on the etiology of the AAO, anatomic considerations, and other patient factors, urgent revascularization with thrombo-embolectomy, direct aortic reconstruction, or anatomic or extra-anatomic bypass procedures may be employed. Aortic reconstruction has been advocated for all patients with infrarenal aortic occlusion given the concern for propagation of thrombosis at the distal aorta proximally to the renal and mesenteric arteries.⁷ Axillary-bifemoral bypass has been advocated as a rapid revascularization strategy with good patency and less physiologic strain for critically ill AAO patients.⁶

The patient in this study had a constellation of risk factors for developing AAO due to thrombosis and consequently sustaining spinal cord infarction. Echocardiography ruled out embolism of a mural thrombus. She had cardiac dysfunction due to atrial fibrillation and left ventricular failure causing a low-flow state (LVEF 30%). She also had a hypercoagulable state due to bladder malignancy in addition to severe atherosclerotic disease. She was not on systemic anticoagulation therapy because of her high fall risk. Hence, her risk for thrombosis was quite high. Despite expedient revascularization surgery, her postoperative course was complicated as a result of severe mesenteric ischemia due to chronic SMA occlusion, which caused her death.

Conclusion

Acute aortic occlusion is a rare vascular emergency. The patient presenting with the abrupt onset of bilateral leg pain, neurologic deficits of paresis/paralysis, sensory disturbance, and/or sphincter dysfunction, and stigmata of vascular compromise with lower extremity mottling should alert the physician to AAO. Acute aortic occlusion continues to have high morbidity and mortality, and prompt recognition and appropriate transfer for surgical intervention are essential for improving outcomes.

Acute aortic occlusion (AAO) is a relatively rare vascular emergency. The actual incidence of AAO is unknown but has been variously reported to be 1% to 4%, and the incidence of AAO secondary to infrarenal abdominal aortic aneurysm is reported to be about 2%.¹ Acute aortic occlusion may present with acute onset of neurologic deficits as a consequence of spinal cord ischemia from thrombotic or embolic etiology. Risk factors for thrombosis include hypertension, tobacco smoking, and diabetes mellitus; heart disease and female gender are associated with embolism.² Spinal cord infarction accounts for only 1% to 2% of all strokes and is characterized by acute onset of paralysis, bowel and bladder dysfunction, and loss of pain and temperature perception. Proprioception and vibratory sense are typically preserved.³ The authors present the case of a patient with acute onset of lower limb paralysis and urinary incontinence who was later found to have AAO due to thrombosis and consequent spinal cord infarction.

Case Presentation

An 80-year-old white woman presented to the emergency department of Jefferson Regional Medical Center in Pine Bluff, Arkansas, with the sudden onset of severe lower back pain, bilateral leg paralysis and paresthesia, and urinary incontinence. The patient stated that she had been watching television when her legs began to tingle and feel numb. Within 10 to 20 minutes she was unable to move her legs and became incontinent of urine. She reported no injury or previous history of back pain. Her medical history was significant for “irregular heartbeat my whole life,” hypertension, hyperlipidemia, and bladder cancer. She was not receiving systemic anticoagulation therapy. She reported a previous 15 pack-year smoking history but reported that she had quit cigarette smoking and usually drank 1 glass of wine daily. She had previously completed 3 rounds of chemotherapy for bladder cancer and received her first radiation treatment earlier that day. The symptoms began about 8 hours later that evening.

On examination the patient was noted to be in acute distress due to pain. Her vital signs in triage were blood pressure (BP) 122/71 mm Hg, pulse 54 beats per min (BPM), respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 90% on 2 L/min oxygen via nasal cannula. Laboratory evaluation was remarkable only for serum sodium 132 mEq/L, potassium 2.8 mEq/L, and thrombocytosis with platelets 697 × 10³/μL. A neurologic examination showed normal motor function, strength of the upper extremities, and paralysis of the lower extremities, which were insensate to blunt or sharp touch and with decreased skin temperature from the groin distally. Pedal pulses were absent bilaterally. She was incontinent of urine and had anal sphincter laxity.

Magnetic resonance imaging showed bulging lumbar intervertebral discs and foraminal narrowing, which the consulting neurosurgeon did not feel explained her presentation and suggested that a vascular etiology was more likely. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis showed occlusion of the infrarenal abdominal aorta, bilateral common, and external iliac arteries. The proximal inferior mesenteric artery was occluded, and there was 90% stenosis of the proximal superior mesenteric artery with noncalcified plaque. There was no abdominal aortic aneurysm or dissection demonstrated. A chest CT was unremarkable.

The patient was started on IV heparin 800 U/h and transferred via ambulance to the University of Arkansas for Medical Sciences in Little Rock, Arkansas, for vascular surgery. On arrival her vital signs were BP 108/69 mm Hg, pulse 123 BPM, respirations 18 breathes per min, temperature 98^° F, and pulse oximetry 94% on 2 L/min oxygen via nasal cannula. The patient’s electrocardiogram demonstrated atrial fibrillation with rapid ventricular response with premature ventricular complexes. On examination the bilateral lower extremities were cyanotic and cold to the touch. The pedal pulses were nonpalpable, and decreased distal sensation with dense paralysis was noted. 

The patient was taken emergently to the operating room (OR) for left axillary bifemoral bypass. Severe atherosclerotic disease was noted at surgery. She was transferred to the surgical intensive care unit (SICU) for postoperative hemodynamic monitoring. Her clinical course became complicated by mesenteric ischemia from chronic superior mesenteric artery (SMA) occlusion. On postoperative day 2, she became progressively more hypotensive, and she was placed on vasopressin 0.04 U/min and amiodarone 0.5 mg/min infusions.

Bedside echocardiography showed diffuse ventricular hypokinesis and a left ventricular ejection fraction (LVEF) of about 30% but no mural thrombus. The patient developed altered mental status and respiratory distress, and her serum lactate increased to 6.1 mg/dL. She was emergently intubated and taken to the OR to attempt recanalization of the SMA occlusion, which was unsuccessful. She was returned to the SICU for continued resuscitation and monitoring. She continued to decline with hypotensive pressures, increasing serum creatinine and lactate, and worsening metabolic acidosis. Management options and goals of care were discussed with the family, and it was decided to honor her do not resuscitate status and pursue comfort care. She was extubated and expired a short time after this was done.

Discussion

Acute aortic occlusion is a rare vascular emergency with a mortality rate that approaches 75%.^4-6 It results from numerous etiologies, including saddle embolism at the aortic bifurcation, acute thrombus formation, subsequent to aortic dissection, or other causes related to severe atherosclerotic disease or hypercoagulable states.^4,7

A recent retrospective series of 29 cases of AAO found that thrombosis was the cause for 76% of cases, and > 40% of patients had a hypercoagulable state either because of antiphospholipid antibody syndrome (17%) or malignancy (24%).⁶ The most common presentation of AAO is the abrupt onset of painful bilateral paresis or paraplegia.^5,6 While some studies have suggested that the major determinant of mortality is time elapsed until revascularization,⁷ other studies have reported that the neurologic status of the extremities is more closely related with mortality.²

The anterior spinal artery is the major independent provider of blood flow to the anterior two-thirds of the spinal cord, including the anterior horns, the anterior commissure, the anterior funiculi, and to a variable extent, the lateral funiculi. The largest segmental posterior radicular branch of the anterior spinal artery is the artery of Adamkiewicz, which arises from the T9 to T12 level on the left in 75% of cases and provides perfusion to the lumbar spinal cord and the conus medullaris. Obstruction of blood flow in this region has been implicated in the clinical picture of anterior cord syndrome characterized by abrupt onset of radicular pain, flaccid paresis or paralysis, sphincter dysfunction with urinary and fecal incontinence, and decreased pain and temperature sensation below a sensory level with spared proprioception and vibratory sensation.^{3, 8-10}

Aortography is the gold standard procedure for diagnosis of AAO, but it is a time-consuming procedure, and preoperative testing is controversial. Contrast-enhanced CT is useful for evaluation as it can be quickly accomplished and is more available in general hospitals. Moreover, CT scanning may reveal aortic dissections or aneurysms as the cause of occlusion. Deep Doppler ultrasonography also has demonstrated utility as a noninvasive and rapidly performed diagnostic procedure. Magnetic resonance angiography or CT should be performed for all cases unless the patient’s clinical condition prevents this evaluation. Imaging not only confirms diagnosis, but also is valuable for assessment and planning management.^11-14

Once the diagnosis of AAO is made, management with IV fluid hydration, heparin administration, and optimizing cardiac function are essential. However, conservative management with anticoagulation alone is associated with high mortality, and unless the ischemia is irreversible or unless the patient is in a dying state, surgery is appropriate.^5,7 Depending on the etiology of the AAO, anatomic considerations, and other patient factors, urgent revascularization with thrombo-embolectomy, direct aortic reconstruction, or anatomic or extra-anatomic bypass procedures may be employed. Aortic reconstruction has been advocated for all patients with infrarenal aortic occlusion given the concern for propagation of thrombosis at the distal aorta proximally to the renal and mesenteric arteries.⁷ Axillary-bifemoral bypass has been advocated as a rapid revascularization strategy with good patency and less physiologic strain for critically ill AAO patients.⁶

The patient in this study had a constellation of risk factors for developing AAO due to thrombosis and consequently sustaining spinal cord infarction. Echocardiography ruled out embolism of a mural thrombus. She had cardiac dysfunction due to atrial fibrillation and left ventricular failure causing a low-flow state (LVEF 30%). She also had a hypercoagulable state due to bladder malignancy in addition to severe atherosclerotic disease. She was not on systemic anticoagulation therapy because of her high fall risk. Hence, her risk for thrombosis was quite high. Despite expedient revascularization surgery, her postoperative course was complicated as a result of severe mesenteric ischemia due to chronic SMA occlusion, which caused her death.

Conclusion

Acute aortic occlusion is a rare vascular emergency. The patient presenting with the abrupt onset of bilateral leg pain, neurologic deficits of paresis/paralysis, sensory disturbance, and/or sphincter dysfunction, and stigmata of vascular compromise with lower extremity mottling should alert the physician to AAO. Acute aortic occlusion continues to have high morbidity and mortality, and prompt recognition and appropriate transfer for surgical intervention are essential for improving outcomes.