Commentary

“Sticks and stones may break my bones, but words will never hurt me.” This mantra was the retort of choice for thousands of apparently resilient premillennial children. But you and I, and just about everyone else, know that words can be very hurtful. A recent article in the journal Eating and Weight Disorders entitled, “ ‘Don’t eat so much’: How parent comments relate to female weight satisfaction” (Eat Weight Disord. 2016 Jun 6. [Epub ahead of print]) reminds us that the pain can last forever.

In a retrospective study of 501 young women aged 20-35 years, the investigators asked whether the women could recall their parents making any comments about their weight when they were young children. What the authors discovered was that even among young women who were of normal weight, those who could recall their parents making a comment about their weight were more dissatisfied with their body weight than the young women who could not recall such a comment. However, if the comment had been about eating habits and not weight, then there was no significant association with weight dissatisfaction.

Before we rush out to send all of the parents of weight-dissatisfied young women on a guilt trip, let’s remember that this was a retrospective study. Let’s consider the not unlikely explanation that there may be something built into the psyche of weight-dissatisfied young women that sharpens their memory for negative comments from friends and family.

Regardless of how we interpret the findings from this study, it is probably safe to say that telling a young girl that she is overweight doesn’t help and should be avoided. This is just another example of how poorly chosen words can be hurtful. But it is also an example of how words alone are seldom shapers of positive behaviors. You can’t talk a picky eater into eating spinach anymore than you can talk the child in the middle of a tantrum into settling down. Good manners are best learned by modeling the behavior of respected adults and not by being subjected to a series of parental lectures. Telling a child she is overweight won’t solve the problem.

So what is the parent of an obese child to do? Unfortunately, many parents of obese children don’t perceive their child as being significantly overweight. But let’s assume we have cleared that hurdle of denial. If telling the child she is overweight is the wrong thing to do, then her parents are forced into using strategies that are subliminal, applied slowly and patiently – silently.

©SolStock/iStock

These strategies could include gradually decreasing the child’s screen time, hoping that it will be replaced by calorie-burning activities; changing the food available for all the inhabitants of the home to increase the likelihood that healthier choices will dominate; and decreasing serving sizes. It is critical that these changes are done so slowly that they go unnoticed by the child. If the child questions the changes, then the response should be that they are being done to help the entire family to be healthier, and that they are not being targeted at any one individual. Of course, the big problem is getting the rest of the family to buy into the changes so that the overweight child doesn’t become a scapegoat.

Shielding the overweight child from the blame game is much easier if the parents have been careful to avoid labeling from the moment they realized or accepted that the child had a weight problem. Here is where we pediatricians can play a critical role in our choice of words, and the setting in which we discuss the child’s weight with the parents. We must point out to the parents that their words can create a hurt that may not ever go away.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

“Sticks and stones may break my bones, but words will never hurt me.” This mantra was the retort of choice for thousands of apparently resilient premillennial children. But you and I, and just about everyone else, know that words can be very hurtful. A recent article in the journal Eating and Weight Disorders entitled, “ ‘Don’t eat so much’: How parent comments relate to female weight satisfaction” (Eat Weight Disord. 2016 Jun 6. [Epub ahead of print]) reminds us that the pain can last forever.

In a retrospective study of 501 young women aged 20-35 years, the investigators asked whether the women could recall their parents making any comments about their weight when they were young children. What the authors discovered was that even among young women who were of normal weight, those who could recall their parents making a comment about their weight were more dissatisfied with their body weight than the young women who could not recall such a comment. However, if the comment had been about eating habits and not weight, then there was no significant association with weight dissatisfaction.

Before we rush out to send all of the parents of weight-dissatisfied young women on a guilt trip, let’s remember that this was a retrospective study. Let’s consider the not unlikely explanation that there may be something built into the psyche of weight-dissatisfied young women that sharpens their memory for negative comments from friends and family.

Regardless of how we interpret the findings from this study, it is probably safe to say that telling a young girl that she is overweight doesn’t help and should be avoided. This is just another example of how poorly chosen words can be hurtful. But it is also an example of how words alone are seldom shapers of positive behaviors. You can’t talk a picky eater into eating spinach anymore than you can talk the child in the middle of a tantrum into settling down. Good manners are best learned by modeling the behavior of respected adults and not by being subjected to a series of parental lectures. Telling a child she is overweight won’t solve the problem.

So what is the parent of an obese child to do? Unfortunately, many parents of obese children don’t perceive their child as being significantly overweight. But let’s assume we have cleared that hurdle of denial. If telling the child she is overweight is the wrong thing to do, then her parents are forced into using strategies that are subliminal, applied slowly and patiently – silently.

©SolStock/iStock

These strategies could include gradually decreasing the child’s screen time, hoping that it will be replaced by calorie-burning activities; changing the food available for all the inhabitants of the home to increase the likelihood that healthier choices will dominate; and decreasing serving sizes. It is critical that these changes are done so slowly that they go unnoticed by the child. If the child questions the changes, then the response should be that they are being done to help the entire family to be healthier, and that they are not being targeted at any one individual. Of course, the big problem is getting the rest of the family to buy into the changes so that the overweight child doesn’t become a scapegoat.

Shielding the overweight child from the blame game is much easier if the parents have been careful to avoid labeling from the moment they realized or accepted that the child had a weight problem. Here is where we pediatricians can play a critical role in our choice of words, and the setting in which we discuss the child’s weight with the parents. We must point out to the parents that their words can create a hurt that may not ever go away.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

“Sticks and stones may break my bones, but words will never hurt me.” This mantra was the retort of choice for thousands of apparently resilient premillennial children. But you and I, and just about everyone else, know that words can be very hurtful. A recent article in the journal Eating and Weight Disorders entitled, “ ‘Don’t eat so much’: How parent comments relate to female weight satisfaction” (Eat Weight Disord. 2016 Jun 6. [Epub ahead of print]) reminds us that the pain can last forever.

In a retrospective study of 501 young women aged 20-35 years, the investigators asked whether the women could recall their parents making any comments about their weight when they were young children. What the authors discovered was that even among young women who were of normal weight, those who could recall their parents making a comment about their weight were more dissatisfied with their body weight than the young women who could not recall such a comment. However, if the comment had been about eating habits and not weight, then there was no significant association with weight dissatisfaction.

Before we rush out to send all of the parents of weight-dissatisfied young women on a guilt trip, let’s remember that this was a retrospective study. Let’s consider the not unlikely explanation that there may be something built into the psyche of weight-dissatisfied young women that sharpens their memory for negative comments from friends and family.

Regardless of how we interpret the findings from this study, it is probably safe to say that telling a young girl that she is overweight doesn’t help and should be avoided. This is just another example of how poorly chosen words can be hurtful. But it is also an example of how words alone are seldom shapers of positive behaviors. You can’t talk a picky eater into eating spinach anymore than you can talk the child in the middle of a tantrum into settling down. Good manners are best learned by modeling the behavior of respected adults and not by being subjected to a series of parental lectures. Telling a child she is overweight won’t solve the problem.

So what is the parent of an obese child to do? Unfortunately, many parents of obese children don’t perceive their child as being significantly overweight. But let’s assume we have cleared that hurdle of denial. If telling the child she is overweight is the wrong thing to do, then her parents are forced into using strategies that are subliminal, applied slowly and patiently – silently.

©SolStock/iStock

These strategies could include gradually decreasing the child’s screen time, hoping that it will be replaced by calorie-burning activities; changing the food available for all the inhabitants of the home to increase the likelihood that healthier choices will dominate; and decreasing serving sizes. It is critical that these changes are done so slowly that they go unnoticed by the child. If the child questions the changes, then the response should be that they are being done to help the entire family to be healthier, and that they are not being targeted at any one individual. Of course, the big problem is getting the rest of the family to buy into the changes so that the overweight child doesn’t become a scapegoat.

Shielding the overweight child from the blame game is much easier if the parents have been careful to avoid labeling from the moment they realized or accepted that the child had a weight problem. Here is where we pediatricians can play a critical role in our choice of words, and the setting in which we discuss the child’s weight with the parents. We must point out to the parents that their words can create a hurt that may not ever go away.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

“10 TIPS FOR OVERCOMING COMMON CHALLENGES OF INTRAPARTUM FETAL MONITORING”
M. SEAN ESPLIN, MD, AND ALEXANDRA G. ELLER, MD, MPH (MAY 2016)

Determining fetal demise
I appreciate and thank Drs. Esplin and Eller for their discussion of fetal monitoring pitfalls. I agree with their sentiment that this is an inexact science. After 40 years of looking at these strips, I am convinced there must be a better way. I look forward to some innovative approach to better determine fetal well-being in labor. This article raises a question I have asked, and sought the answer to, for years.

On occasion, I have diagnosed intrauterine fetal demise by detecting the maternal heart rate with an internal fetal scalp electrode. On one particular occasion, somewhere between the time of admission, spontaneous rupture of membranes, and applying the fetal scalp electrode, the fetus died. This case was similar to the one you describe in which early efforts with the external Doppler were unsatisfactory and fetal status was suspect. My question: “What is the time interval from the moment of fetal death and loss of fetal electrical activity until the fetus becomes an effective conduit for the conduction of the maternal cardiac signal? Is it minutes, hours, days? Clearly, this would be difficult to evaluate other than on animal models, but I have yet to find an answer.

Edward Hall, MD
Edgewood, Kentucky

Drs. Esplin and Eller respond
We are grateful for your interest in our article. Unfortunately the answer to your question about the timing between fetal demise and the appearance of maternal electrocardiac activity detected by a fetal scalp electrode after transmission through the fetal body is not clear. We are not aware of any data that would conclusively prove the time required for this to occur. It is likely that this type of information would require an animal model to elucidate. However, we are aware of at least 2 clinical cases in which fetal cardiac activity was convincingly documented at admission and for several hours intrapartum with subsequent episodic loss of signal and then delivery of a dead fetus wherein retrospective review confirmed that for a period of time the maternal heart rate was recorded and interpreted to be the fetal heart rate. From these experiences we conclude that this is possible shortly after the fetal demise, likely within minutes to hours.

Despite this uncertainty, we are confident that the information in our article will help clinicians identify and correct those instances when the maternal heart rate is being recorded instead of the fetal heart rate. Fortunately, this rarely involves a situation in which there has been an undiagnosed intrauterine fetal demise.

“SERMs IN MENOPAUSE: MATCHING AGENTS TO PATIENTS’ SYMPTOMS AND ATTRIBUTES”
JAMES H. LIU, MD, AND GRETCHEN COLLINS, MD (MAY 2016 Special issue)

“SERMs” definition inaccurate
I disagree with Drs. Liu and Collins’ description of selective estrogen receptor modulators (SERMs) on page S18, in which they state, “Estrogens and SERMs are lipid-soluble steroid hormones that bind to 2 specific hormone receptors, estrogen receptor α and estrogen receptor β…” SERMs are not hormones, and they are defined improperly as such.

Gideon G. Panter, MD
New York, New York

Drs. Liu and Collins respond
Thank you for your interest in our article. SERMs are typically synthetic organic compounds that can activate estrogen receptors or modify activity of the estrogen receptor and, thus, can be considered hormones.

“START OFFERING ASPIRIN TO PREGNANT WOMEN AT HIGH RISK FOR PREECLAMPSIA”
ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2016)

Stop aspirin in pregnancy?
Like many colleagues, I had been stopping low-dose aspirin prior to planned or expected delivery. Evidence suggests a bigger risk of rebound hypercoagulability than bleeding after stopping low-dose aspirin, according to an article on aspirin use in the perioperative period.¹ Because of lack of benefit and increased risks of stopping aspirin, it may be time to change our practice and continue aspirin to minimize peridelivery thromboembolic risk.

Mark Jacobs, MD
Mill Valley, CA

Reference

Dr. Barbieri responds
I thank Dr. Jacobs for his advice to continue low-dose aspirin throughout pregnancy in women taking aspirin for prevention of preeclampsia. The review he references is focused on elderly patients taking aspirin for existing heart disease, which is a very different population than pregnant women. There are no high-quality data from clinical trials on whether to continue or stop low-dose aspirin in pregnant women as they approach their due date. I think obstetricians can use their best judgment in making the decision of whether to stop low-dose aspirin at 36 or 37 weeks or continue aspirin throughout the pregnancy.

“CESAREAN SCAR DEFECT:WHAT IS IT AND HOW SHOULD IT BE TREATED?”
CAMRAN NEZHAT, MD; LINDSEY GRACE, MD;ROSE SOLIEMANNJAD, BS;GITY MESHKAT RAZAVI, MD; AND AZADEH NEZHAT, MD (APRIL 2016)

Technique for preventing cesarean scar defect
I read with interest the proposed treatment options that Dr. Nezhat and colleagues suggested for cesarean scar defect. However, nowhere did I see mention of preventing this defect.

For 30 years I have been closing the hysterotomy in a fashion that I believe leaves no presence of an isthmocele and is a superior closure. I overlap the upper flap with the lower flap and, most importantly, close with chromic catgut. A cesarean scar “niche” occurs with involution of the uterus causing the suture line to bunch up. Chromic catgut has a shorter half-life and will “give;” a suture made of polypropylene will not stretch. I use a running interlocking line with sutures about 0.5 inches apart.

Donald M. Werner, MD
Binghamton, New York

Dr. Nezhat and colleagues respond
We thank Dr. Werner for his inquiry regarding the prevention of cesarean scar defects; as we all agree, the best treatment is prevention. As mentioned in our article, there are no definitive results from the studies published to date that show superiority of one surgical technique over another in regard to hysterotomy closure and prevention of cesarean scar defects. Possible risk factors for developing cesarean scar defects include low (cervical) hysterotomy, single-layer uterine wall closure, use of locking sutures, closure of hysterotomy with endometrial-sparing technique, and multiple cesarean deliveries. Although these factors may be associated with increased risk of cesarean scar defects, additional randomized controlled trials need to be performed prior to being able to offer a recommendation on a conclusive preventative measure. For additional information, I would direct you to references 3 and 4 in our article. We thank you for sharing your positive experience and eagerly await additional studies on the topic.

Share your thoughts! Send your Letter to the Editor to [email protected]

“10 TIPS FOR OVERCOMING COMMON CHALLENGES OF INTRAPARTUM FETAL MONITORING”
M. SEAN ESPLIN, MD, AND ALEXANDRA G. ELLER, MD, MPH (MAY 2016)

Determining fetal demise
I appreciate and thank Drs. Esplin and Eller for their discussion of fetal monitoring pitfalls. I agree with their sentiment that this is an inexact science. After 40 years of looking at these strips, I am convinced there must be a better way. I look forward to some innovative approach to better determine fetal well-being in labor. This article raises a question I have asked, and sought the answer to, for years.

On occasion, I have diagnosed intrauterine fetal demise by detecting the maternal heart rate with an internal fetal scalp electrode. On one particular occasion, somewhere between the time of admission, spontaneous rupture of membranes, and applying the fetal scalp electrode, the fetus died. This case was similar to the one you describe in which early efforts with the external Doppler were unsatisfactory and fetal status was suspect. My question: “What is the time interval from the moment of fetal death and loss of fetal electrical activity until the fetus becomes an effective conduit for the conduction of the maternal cardiac signal? Is it minutes, hours, days? Clearly, this would be difficult to evaluate other than on animal models, but I have yet to find an answer.

Edward Hall, MD
Edgewood, Kentucky

Drs. Esplin and Eller respond
We are grateful for your interest in our article. Unfortunately the answer to your question about the timing between fetal demise and the appearance of maternal electrocardiac activity detected by a fetal scalp electrode after transmission through the fetal body is not clear. We are not aware of any data that would conclusively prove the time required for this to occur. It is likely that this type of information would require an animal model to elucidate. However, we are aware of at least 2 clinical cases in which fetal cardiac activity was convincingly documented at admission and for several hours intrapartum with subsequent episodic loss of signal and then delivery of a dead fetus wherein retrospective review confirmed that for a period of time the maternal heart rate was recorded and interpreted to be the fetal heart rate. From these experiences we conclude that this is possible shortly after the fetal demise, likely within minutes to hours.

Despite this uncertainty, we are confident that the information in our article will help clinicians identify and correct those instances when the maternal heart rate is being recorded instead of the fetal heart rate. Fortunately, this rarely involves a situation in which there has been an undiagnosed intrauterine fetal demise.

“SERMs IN MENOPAUSE: MATCHING AGENTS TO PATIENTS’ SYMPTOMS AND ATTRIBUTES”
JAMES H. LIU, MD, AND GRETCHEN COLLINS, MD (MAY 2016 Special issue)

“SERMs” definition inaccurate
I disagree with Drs. Liu and Collins’ description of selective estrogen receptor modulators (SERMs) on page S18, in which they state, “Estrogens and SERMs are lipid-soluble steroid hormones that bind to 2 specific hormone receptors, estrogen receptor α and estrogen receptor β…” SERMs are not hormones, and they are defined improperly as such.

Gideon G. Panter, MD
New York, New York

Drs. Liu and Collins respond
Thank you for your interest in our article. SERMs are typically synthetic organic compounds that can activate estrogen receptors or modify activity of the estrogen receptor and, thus, can be considered hormones.

“START OFFERING ASPIRIN TO PREGNANT WOMEN AT HIGH RISK FOR PREECLAMPSIA”
ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2016)

Stop aspirin in pregnancy?
Like many colleagues, I had been stopping low-dose aspirin prior to planned or expected delivery. Evidence suggests a bigger risk of rebound hypercoagulability than bleeding after stopping low-dose aspirin, according to an article on aspirin use in the perioperative period.¹ Because of lack of benefit and increased risks of stopping aspirin, it may be time to change our practice and continue aspirin to minimize peridelivery thromboembolic risk.

Mark Jacobs, MD
Mill Valley, CA

Reference

Dr. Barbieri responds
I thank Dr. Jacobs for his advice to continue low-dose aspirin throughout pregnancy in women taking aspirin for prevention of preeclampsia. The review he references is focused on elderly patients taking aspirin for existing heart disease, which is a very different population than pregnant women. There are no high-quality data from clinical trials on whether to continue or stop low-dose aspirin in pregnant women as they approach their due date. I think obstetricians can use their best judgment in making the decision of whether to stop low-dose aspirin at 36 or 37 weeks or continue aspirin throughout the pregnancy.

“CESAREAN SCAR DEFECT:WHAT IS IT AND HOW SHOULD IT BE TREATED?”
CAMRAN NEZHAT, MD; LINDSEY GRACE, MD;ROSE SOLIEMANNJAD, BS;GITY MESHKAT RAZAVI, MD; AND AZADEH NEZHAT, MD (APRIL 2016)

Technique for preventing cesarean scar defect
I read with interest the proposed treatment options that Dr. Nezhat and colleagues suggested for cesarean scar defect. However, nowhere did I see mention of preventing this defect.

For 30 years I have been closing the hysterotomy in a fashion that I believe leaves no presence of an isthmocele and is a superior closure. I overlap the upper flap with the lower flap and, most importantly, close with chromic catgut. A cesarean scar “niche” occurs with involution of the uterus causing the suture line to bunch up. Chromic catgut has a shorter half-life and will “give;” a suture made of polypropylene will not stretch. I use a running interlocking line with sutures about 0.5 inches apart.

Donald M. Werner, MD
Binghamton, New York

Dr. Nezhat and colleagues respond
We thank Dr. Werner for his inquiry regarding the prevention of cesarean scar defects; as we all agree, the best treatment is prevention. As mentioned in our article, there are no definitive results from the studies published to date that show superiority of one surgical technique over another in regard to hysterotomy closure and prevention of cesarean scar defects. Possible risk factors for developing cesarean scar defects include low (cervical) hysterotomy, single-layer uterine wall closure, use of locking sutures, closure of hysterotomy with endometrial-sparing technique, and multiple cesarean deliveries. Although these factors may be associated with increased risk of cesarean scar defects, additional randomized controlled trials need to be performed prior to being able to offer a recommendation on a conclusive preventative measure. For additional information, I would direct you to references 3 and 4 in our article. We thank you for sharing your positive experience and eagerly await additional studies on the topic.

Share your thoughts! Send your Letter to the Editor to [email protected]

“10 TIPS FOR OVERCOMING COMMON CHALLENGES OF INTRAPARTUM FETAL MONITORING”
M. SEAN ESPLIN, MD, AND ALEXANDRA G. ELLER, MD, MPH (MAY 2016)

Determining fetal demise
I appreciate and thank Drs. Esplin and Eller for their discussion of fetal monitoring pitfalls. I agree with their sentiment that this is an inexact science. After 40 years of looking at these strips, I am convinced there must be a better way. I look forward to some innovative approach to better determine fetal well-being in labor. This article raises a question I have asked, and sought the answer to, for years.

On occasion, I have diagnosed intrauterine fetal demise by detecting the maternal heart rate with an internal fetal scalp electrode. On one particular occasion, somewhere between the time of admission, spontaneous rupture of membranes, and applying the fetal scalp electrode, the fetus died. This case was similar to the one you describe in which early efforts with the external Doppler were unsatisfactory and fetal status was suspect. My question: “What is the time interval from the moment of fetal death and loss of fetal electrical activity until the fetus becomes an effective conduit for the conduction of the maternal cardiac signal? Is it minutes, hours, days? Clearly, this would be difficult to evaluate other than on animal models, but I have yet to find an answer.

Edward Hall, MD
Edgewood, Kentucky

Drs. Esplin and Eller respond
We are grateful for your interest in our article. Unfortunately the answer to your question about the timing between fetal demise and the appearance of maternal electrocardiac activity detected by a fetal scalp electrode after transmission through the fetal body is not clear. We are not aware of any data that would conclusively prove the time required for this to occur. It is likely that this type of information would require an animal model to elucidate. However, we are aware of at least 2 clinical cases in which fetal cardiac activity was convincingly documented at admission and for several hours intrapartum with subsequent episodic loss of signal and then delivery of a dead fetus wherein retrospective review confirmed that for a period of time the maternal heart rate was recorded and interpreted to be the fetal heart rate. From these experiences we conclude that this is possible shortly after the fetal demise, likely within minutes to hours.

Despite this uncertainty, we are confident that the information in our article will help clinicians identify and correct those instances when the maternal heart rate is being recorded instead of the fetal heart rate. Fortunately, this rarely involves a situation in which there has been an undiagnosed intrauterine fetal demise.

“SERMs IN MENOPAUSE: MATCHING AGENTS TO PATIENTS’ SYMPTOMS AND ATTRIBUTES”
JAMES H. LIU, MD, AND GRETCHEN COLLINS, MD (MAY 2016 Special issue)

“SERMs” definition inaccurate
I disagree with Drs. Liu and Collins’ description of selective estrogen receptor modulators (SERMs) on page S18, in which they state, “Estrogens and SERMs are lipid-soluble steroid hormones that bind to 2 specific hormone receptors, estrogen receptor α and estrogen receptor β…” SERMs are not hormones, and they are defined improperly as such.

Gideon G. Panter, MD
New York, New York

Drs. Liu and Collins respond
Thank you for your interest in our article. SERMs are typically synthetic organic compounds that can activate estrogen receptors or modify activity of the estrogen receptor and, thus, can be considered hormones.

“START OFFERING ASPIRIN TO PREGNANT WOMEN AT HIGH RISK FOR PREECLAMPSIA”
ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2016)

Stop aspirin in pregnancy?
Like many colleagues, I had been stopping low-dose aspirin prior to planned or expected delivery. Evidence suggests a bigger risk of rebound hypercoagulability than bleeding after stopping low-dose aspirin, according to an article on aspirin use in the perioperative period.¹ Because of lack of benefit and increased risks of stopping aspirin, it may be time to change our practice and continue aspirin to minimize peridelivery thromboembolic risk.

Mark Jacobs, MD
Mill Valley, CA

Reference

Dr. Barbieri responds
I thank Dr. Jacobs for his advice to continue low-dose aspirin throughout pregnancy in women taking aspirin for prevention of preeclampsia. The review he references is focused on elderly patients taking aspirin for existing heart disease, which is a very different population than pregnant women. There are no high-quality data from clinical trials on whether to continue or stop low-dose aspirin in pregnant women as they approach their due date. I think obstetricians can use their best judgment in making the decision of whether to stop low-dose aspirin at 36 or 37 weeks or continue aspirin throughout the pregnancy.

“CESAREAN SCAR DEFECT:WHAT IS IT AND HOW SHOULD IT BE TREATED?”
CAMRAN NEZHAT, MD; LINDSEY GRACE, MD;ROSE SOLIEMANNJAD, BS;GITY MESHKAT RAZAVI, MD; AND AZADEH NEZHAT, MD (APRIL 2016)

Technique for preventing cesarean scar defect
I read with interest the proposed treatment options that Dr. Nezhat and colleagues suggested for cesarean scar defect. However, nowhere did I see mention of preventing this defect.

For 30 years I have been closing the hysterotomy in a fashion that I believe leaves no presence of an isthmocele and is a superior closure. I overlap the upper flap with the lower flap and, most importantly, close with chromic catgut. A cesarean scar “niche” occurs with involution of the uterus causing the suture line to bunch up. Chromic catgut has a shorter half-life and will “give;” a suture made of polypropylene will not stretch. I use a running interlocking line with sutures about 0.5 inches apart.

Donald M. Werner, MD
Binghamton, New York

Dr. Nezhat and colleagues respond
We thank Dr. Werner for his inquiry regarding the prevention of cesarean scar defects; as we all agree, the best treatment is prevention. As mentioned in our article, there are no definitive results from the studies published to date that show superiority of one surgical technique over another in regard to hysterotomy closure and prevention of cesarean scar defects. Possible risk factors for developing cesarean scar defects include low (cervical) hysterotomy, single-layer uterine wall closure, use of locking sutures, closure of hysterotomy with endometrial-sparing technique, and multiple cesarean deliveries. Although these factors may be associated with increased risk of cesarean scar defects, additional randomized controlled trials need to be performed prior to being able to offer a recommendation on a conclusive preventative measure. For additional information, I would direct you to references 3 and 4 in our article. We thank you for sharing your positive experience and eagerly await additional studies on the topic.

Share your thoughts! Send your Letter to the Editor to [email protected]

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

I recently saw a 73-year-old Hispanic woman in the emergency department who said (through her daughter, who was translating) that she was experiencing mild headache, shortness of breath, and throat swelling. She had previously sought care for these complaints, but her condition had not improved. Her past medical and surgical history was otherwise unremarkable.

On examination, her voice was hoarse and she had bilateral 1+ pitting edema of her lower extremities. Her vital signs were stable, her lungs were clear, her throat appeared normal, and she didn’t have any skin rashes. However, her lab results included a white blood cell count of 2100/mcL, platelet count of 73,000/mcL, and an absolute neutrophil count of 1000/mm³. Her b-type natriuretic peptide, cardiac marker, and thyroid-stimulating hormone levels were normal.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not. That is, until we learned about a drug the patient had obtained in Mexico.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not.

I gathered a more detailed history and learned that the patient had been living in the United States for years, but she occasionally returned to Mexico for visits and routine medical care. During one of these trips, she’d obtained metamizole—a drug banned in the United States—and was taking it for her headaches.

A Web search revealed rare adverse effects of agranulocytosis, neutropenia, and anaphylaxis from metamizole. It is highly probable that the metamizole caused my patient’s symptoms and abnormal labs findings. I advised her of my suspicions and recommended that she stop taking the medication. A hospitalist then took over her care.

The key takeaway from this case is to account for all medications when gathering a patient’s history, including those that may be obtained outside of the United States.

Nick Ly, DO
Lillington, NC

I recently saw a 73-year-old Hispanic woman in the emergency department who said (through her daughter, who was translating) that she was experiencing mild headache, shortness of breath, and throat swelling. She had previously sought care for these complaints, but her condition had not improved. Her past medical and surgical history was otherwise unremarkable.

On examination, her voice was hoarse and she had bilateral 1+ pitting edema of her lower extremities. Her vital signs were stable, her lungs were clear, her throat appeared normal, and she didn’t have any skin rashes. However, her lab results included a white blood cell count of 2100/mcL, platelet count of 73,000/mcL, and an absolute neutrophil count of 1000/mm³. Her b-type natriuretic peptide, cardiac marker, and thyroid-stimulating hormone levels were normal.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not. That is, until we learned about a drug the patient had obtained in Mexico.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not.

I gathered a more detailed history and learned that the patient had been living in the United States for years, but she occasionally returned to Mexico for visits and routine medical care. During one of these trips, she’d obtained metamizole—a drug banned in the United States—and was taking it for her headaches.

A Web search revealed rare adverse effects of agranulocytosis, neutropenia, and anaphylaxis from metamizole. It is highly probable that the metamizole caused my patient’s symptoms and abnormal labs findings. I advised her of my suspicions and recommended that she stop taking the medication. A hospitalist then took over her care.

The key takeaway from this case is to account for all medications when gathering a patient’s history, including those that may be obtained outside of the United States.

Nick Ly, DO
Lillington, NC

I recently saw a 73-year-old Hispanic woman in the emergency department who said (through her daughter, who was translating) that she was experiencing mild headache, shortness of breath, and throat swelling. She had previously sought care for these complaints, but her condition had not improved. Her past medical and surgical history was otherwise unremarkable.

On examination, her voice was hoarse and she had bilateral 1+ pitting edema of her lower extremities. Her vital signs were stable, her lungs were clear, her throat appeared normal, and she didn’t have any skin rashes. However, her lab results included a white blood cell count of 2100/mcL, platelet count of 73,000/mcL, and an absolute neutrophil count of 1000/mm³. Her b-type natriuretic peptide, cardiac marker, and thyroid-stimulating hormone levels were normal.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not. That is, until we learned about a drug the patient had obtained in Mexico.

The diagnosis was clear—neutropenia and agranulocytosis—although the cause was not.

I gathered a more detailed history and learned that the patient had been living in the United States for years, but she occasionally returned to Mexico for visits and routine medical care. During one of these trips, she’d obtained metamizole—a drug banned in the United States—and was taking it for her headaches.

A Web search revealed rare adverse effects of agranulocytosis, neutropenia, and anaphylaxis from metamizole. It is highly probable that the metamizole caused my patient’s symptoms and abnormal labs findings. I advised her of my suspicions and recommended that she stop taking the medication. A hospitalist then took over her care.

The key takeaway from this case is to account for all medications when gathering a patient’s history, including those that may be obtained outside of the United States.

Nick Ly, DO
Lillington, NC

As a scribe and accepted future medical student, I was quite interested in the article, “Medical scribes: How do their notes stack up?” by Misra-Hebert, et al (J Fam Pract. 2016;65:155-159) and the editorial, “Working with scribes—the good, the surprising” (J Fam Pract. 2016;65:154,176) in the March issue. I was struck, however, that both pieces implied that only medical assistants (MAs) are scribes.

I am familiar with practices where MAs assume a “documentation support” function in addition to their traditional role, and I currently work in a practice with professional scribes. Professional scribes are often recent college graduates who are working before beginning their studies to become a physician or physician assistant.

In my experience, MAs want to do the work they were hired and trained to do and are not enthusiastic about extensive charting. However, professional scribes apply to the position expecting to do this very task, with the goals of learning from the doctor-patient interaction, deepening their medical knowledge, and becoming comfortable in a clinical setting.

Although I am glad to see that MAs improve documentation quality per the original research mentioned above, it would be beneficial to compare the outcomes of professional scribes to those of cross-trained MAs or to traditional providers who do their own note-writing.

D. Brendan Johnson, BA
Minneapolis, Minn

As a scribe and accepted future medical student, I was quite interested in the article, “Medical scribes: How do their notes stack up?” by Misra-Hebert, et al (J Fam Pract. 2016;65:155-159) and the editorial, “Working with scribes—the good, the surprising” (J Fam Pract. 2016;65:154,176) in the March issue. I was struck, however, that both pieces implied that only medical assistants (MAs) are scribes.

I am familiar with practices where MAs assume a “documentation support” function in addition to their traditional role, and I currently work in a practice with professional scribes. Professional scribes are often recent college graduates who are working before beginning their studies to become a physician or physician assistant.

In my experience, MAs want to do the work they were hired and trained to do and are not enthusiastic about extensive charting. However, professional scribes apply to the position expecting to do this very task, with the goals of learning from the doctor-patient interaction, deepening their medical knowledge, and becoming comfortable in a clinical setting.

Although I am glad to see that MAs improve documentation quality per the original research mentioned above, it would be beneficial to compare the outcomes of professional scribes to those of cross-trained MAs or to traditional providers who do their own note-writing.

D. Brendan Johnson, BA
Minneapolis, Minn

As a scribe and accepted future medical student, I was quite interested in the article, “Medical scribes: How do their notes stack up?” by Misra-Hebert, et al (J Fam Pract. 2016;65:155-159) and the editorial, “Working with scribes—the good, the surprising” (J Fam Pract. 2016;65:154,176) in the March issue. I was struck, however, that both pieces implied that only medical assistants (MAs) are scribes.

I am familiar with practices where MAs assume a “documentation support” function in addition to their traditional role, and I currently work in a practice with professional scribes. Professional scribes are often recent college graduates who are working before beginning their studies to become a physician or physician assistant.

In my experience, MAs want to do the work they were hired and trained to do and are not enthusiastic about extensive charting. However, professional scribes apply to the position expecting to do this very task, with the goals of learning from the doctor-patient interaction, deepening their medical knowledge, and becoming comfortable in a clinical setting.

Although I am glad to see that MAs improve documentation quality per the original research mentioned above, it would be beneficial to compare the outcomes of professional scribes to those of cross-trained MAs or to traditional providers who do their own note-writing.

D. Brendan Johnson, BA
Minneapolis, Minn

Gun violence, the LGBT community, and terrorism. Who would have imagined these 3 entities tragically colliding in Orlando last month, in the shadow of “the happiest place on earth”? The tragedy was all too real for the victims—mostly gay young Hispanic men—their families and friends, and all those who responded with urgent help. Our hearts go out to the victims and their loved ones, and our hats go off to those who rushed in to help—especially the dedicated law enforcement and medical personnel who saved many lives.

We respond as a nation and as individuals with great sadness and anger to an event like this. But are there lessons embedded in the sorrow for us as family physicians and primary care clinicians? I believe there are.

1. Ask yourself: Am I doing all I can to provide compassionate care? Although I think of myself as a caring, compassionate family physician who treats all patients equally, I realize that I must continue to educate myself about the culture and health needs of specific segments of my patient population to ensure that I provide truly excellent care. Traditionally, cultural sensitivity training has focused on knowledge of races, ethnicities, and cultures, but it must also include training about sexual orientation. Asking patients about their sexual orientation must be a routine part of the medical history.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. What can we do to prevent and mitigate these evils?

One of the minority groups we know least about is transgender individuals, who have unique medical and psychological issues. It is tragically ironic that we had planned an article about caring for transgender patients—a group that experiences disproportionate discrimination and violence¹—for this issue of JFP long before the Orlando shooting. We still have much to learn about the most appropriate way of caring for transgender individuals because there has been so little research.

2. Treat gun violence like an infectious disease. Another lesson from the Orlando tragedy is to approach the issue of gun violence—which is always highly politicized and charged in this country—as a public health problem. One of the best examples of this approach in action is an organization called Cure Violence (cureviolence.org) led by Gary Slutkin, MD, a former Centers for Disease Control and Prevention infectious disease specialist and epidemiologist. The organization proposes that the best way to stop violence is by using the methods and strategies associated with disease control. The group claims to have made great strides in reducing violence in the communities in which it works by treating violence as an epidemic.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. We all must do our small, but important, part as health professionals to prevent and mitigate these evils.

Gun violence, the LGBT community, and terrorism. Who would have imagined these 3 entities tragically colliding in Orlando last month, in the shadow of “the happiest place on earth”? The tragedy was all too real for the victims—mostly gay young Hispanic men—their families and friends, and all those who responded with urgent help. Our hearts go out to the victims and their loved ones, and our hats go off to those who rushed in to help—especially the dedicated law enforcement and medical personnel who saved many lives.

We respond as a nation and as individuals with great sadness and anger to an event like this. But are there lessons embedded in the sorrow for us as family physicians and primary care clinicians? I believe there are.

1. Ask yourself: Am I doing all I can to provide compassionate care? Although I think of myself as a caring, compassionate family physician who treats all patients equally, I realize that I must continue to educate myself about the culture and health needs of specific segments of my patient population to ensure that I provide truly excellent care. Traditionally, cultural sensitivity training has focused on knowledge of races, ethnicities, and cultures, but it must also include training about sexual orientation. Asking patients about their sexual orientation must be a routine part of the medical history.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. What can we do to prevent and mitigate these evils?

One of the minority groups we know least about is transgender individuals, who have unique medical and psychological issues. It is tragically ironic that we had planned an article about caring for transgender patients—a group that experiences disproportionate discrimination and violence¹—for this issue of JFP long before the Orlando shooting. We still have much to learn about the most appropriate way of caring for transgender individuals because there has been so little research.

2. Treat gun violence like an infectious disease. Another lesson from the Orlando tragedy is to approach the issue of gun violence—which is always highly politicized and charged in this country—as a public health problem. One of the best examples of this approach in action is an organization called Cure Violence (cureviolence.org) led by Gary Slutkin, MD, a former Centers for Disease Control and Prevention infectious disease specialist and epidemiologist. The organization proposes that the best way to stop violence is by using the methods and strategies associated with disease control. The group claims to have made great strides in reducing violence in the communities in which it works by treating violence as an epidemic.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. We all must do our small, but important, part as health professionals to prevent and mitigate these evils.

Gun violence, the LGBT community, and terrorism. Who would have imagined these 3 entities tragically colliding in Orlando last month, in the shadow of “the happiest place on earth”? The tragedy was all too real for the victims—mostly gay young Hispanic men—their families and friends, and all those who responded with urgent help. Our hearts go out to the victims and their loved ones, and our hats go off to those who rushed in to help—especially the dedicated law enforcement and medical personnel who saved many lives.

We respond as a nation and as individuals with great sadness and anger to an event like this. But are there lessons embedded in the sorrow for us as family physicians and primary care clinicians? I believe there are.

1. Ask yourself: Am I doing all I can to provide compassionate care? Although I think of myself as a caring, compassionate family physician who treats all patients equally, I realize that I must continue to educate myself about the culture and health needs of specific segments of my patient population to ensure that I provide truly excellent care. Traditionally, cultural sensitivity training has focused on knowledge of races, ethnicities, and cultures, but it must also include training about sexual orientation. Asking patients about their sexual orientation must be a routine part of the medical history.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. What can we do to prevent and mitigate these evils?

One of the minority groups we know least about is transgender individuals, who have unique medical and psychological issues. It is tragically ironic that we had planned an article about caring for transgender patients—a group that experiences disproportionate discrimination and violence¹—for this issue of JFP long before the Orlando shooting. We still have much to learn about the most appropriate way of caring for transgender individuals because there has been so little research.

2. Treat gun violence like an infectious disease. Another lesson from the Orlando tragedy is to approach the issue of gun violence—which is always highly politicized and charged in this country—as a public health problem. One of the best examples of this approach in action is an organization called Cure Violence (cureviolence.org) led by Gary Slutkin, MD, a former Centers for Disease Control and Prevention infectious disease specialist and epidemiologist. The organization proposes that the best way to stop violence is by using the methods and strategies associated with disease control. The group claims to have made great strides in reducing violence in the communities in which it works by treating violence as an epidemic.

Violence and discrimination, like chronic disease, seem to be permanent fixtures on the human landscape. We all must do our small, but important, part as health professionals to prevent and mitigate these evils.

In 1996, 2 exposure incidents sparked a movement to better understand children’s environmental health. In both incidents, children were exposed to significant toxicants in unexpected ways. In one, the organophosphate insecticide methyl parathion was applied illegally in indoor settings.¹ In another, elemental mercury residue was detected in apartments converted from a fluorescent bulb facility.² These incidents, and others like them, alerted physicians and government agencies to the collective lack of training and experience in the field of pediatric environmental health.

To address the situation, the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency created the Pediatric Environmental Health Specialty Unit (PEHSU) program. The program, which is now jointly operated by the American College of Medical Toxicology and the American Academy of Pediatrics, maintains sites in 10 regions³ and seeks to enhance education and promote consultation and referral related to reproductive and children’s environmental health.

This past fall, PEHSU updated its Web site at www.pehsu.net, which provides information, training, and resources for health professionals and the general public. The Web site provides news, fact sheets, and online education regarding environment-related pediatric and reproductive health issues. It also provides a tool for finding a local expert in the PEHSU national network, should a family physician need to refer a patient for more extensive assistance.

We believe that family physicians will find the PEHSU program resources informative, educational, and relevant to their practice.

Carl R. Baum, MD, FAAP, FACMT, Medical Director
Dana Turner, MPH, CHES
Amanda Allen, MS
PEHSU Program
National Office—West
Phoenix, Ariz

References

1. Esteban E, Rubin C, Hill R, et al. Association between indoor residential contamination with methyl parathion and urinary para-nitrophenol. J Expo Anal Environ Epidemiol. 1996;6:375-387.

2. Centers for Disease Control and Prevention (CDC). Mercury exposure among residents of a building formerly used for industrial purposes—New Jersey, 1995. MMWR Morb Mortal Wkly Rep. 1996;45:422-424.

3. Wilborne-Davis P, Kirkland KH, Mulloy KB. A model for physician education and consultation in pediatric environmental health—the Pediatric Environmental Health Specialty Units (PEHSU) program. Pediatr Clin North Am. 2007;54:1-13.

In 1996, 2 exposure incidents sparked a movement to better understand children’s environmental health. In both incidents, children were exposed to significant toxicants in unexpected ways. In one, the organophosphate insecticide methyl parathion was applied illegally in indoor settings.¹ In another, elemental mercury residue was detected in apartments converted from a fluorescent bulb facility.² These incidents, and others like them, alerted physicians and government agencies to the collective lack of training and experience in the field of pediatric environmental health.

To address the situation, the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency created the Pediatric Environmental Health Specialty Unit (PEHSU) program. The program, which is now jointly operated by the American College of Medical Toxicology and the American Academy of Pediatrics, maintains sites in 10 regions³ and seeks to enhance education and promote consultation and referral related to reproductive and children’s environmental health.

This past fall, PEHSU updated its Web site at www.pehsu.net, which provides information, training, and resources for health professionals and the general public. The Web site provides news, fact sheets, and online education regarding environment-related pediatric and reproductive health issues. It also provides a tool for finding a local expert in the PEHSU national network, should a family physician need to refer a patient for more extensive assistance.

We believe that family physicians will find the PEHSU program resources informative, educational, and relevant to their practice.

Carl R. Baum, MD, FAAP, FACMT, Medical Director
Dana Turner, MPH, CHES
Amanda Allen, MS
PEHSU Program
National Office—West
Phoenix, Ariz

References

1. Esteban E, Rubin C, Hill R, et al. Association between indoor residential contamination with methyl parathion and urinary para-nitrophenol. J Expo Anal Environ Epidemiol. 1996;6:375-387.

2. Centers for Disease Control and Prevention (CDC). Mercury exposure among residents of a building formerly used for industrial purposes—New Jersey, 1995. MMWR Morb Mortal Wkly Rep. 1996;45:422-424.

3. Wilborne-Davis P, Kirkland KH, Mulloy KB. A model for physician education and consultation in pediatric environmental health—the Pediatric Environmental Health Specialty Units (PEHSU) program. Pediatr Clin North Am. 2007;54:1-13.

In 1996, 2 exposure incidents sparked a movement to better understand children’s environmental health. In both incidents, children were exposed to significant toxicants in unexpected ways. In one, the organophosphate insecticide methyl parathion was applied illegally in indoor settings.¹ In another, elemental mercury residue was detected in apartments converted from a fluorescent bulb facility.² These incidents, and others like them, alerted physicians and government agencies to the collective lack of training and experience in the field of pediatric environmental health.

To address the situation, the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency created the Pediatric Environmental Health Specialty Unit (PEHSU) program. The program, which is now jointly operated by the American College of Medical Toxicology and the American Academy of Pediatrics, maintains sites in 10 regions³ and seeks to enhance education and promote consultation and referral related to reproductive and children’s environmental health.

This past fall, PEHSU updated its Web site at www.pehsu.net, which provides information, training, and resources for health professionals and the general public. The Web site provides news, fact sheets, and online education regarding environment-related pediatric and reproductive health issues. It also provides a tool for finding a local expert in the PEHSU national network, should a family physician need to refer a patient for more extensive assistance.

We believe that family physicians will find the PEHSU program resources informative, educational, and relevant to their practice.

Carl R. Baum, MD, FAAP, FACMT, Medical Director
Dana Turner, MPH, CHES
Amanda Allen, MS
PEHSU Program
National Office—West
Phoenix, Ariz

References

1. Esteban E, Rubin C, Hill R, et al. Association between indoor residential contamination with methyl parathion and urinary para-nitrophenol. J Expo Anal Environ Epidemiol. 1996;6:375-387.

2. Centers for Disease Control and Prevention (CDC). Mercury exposure among residents of a building formerly used for industrial purposes—New Jersey, 1995. MMWR Morb Mortal Wkly Rep. 1996;45:422-424.

3. Wilborne-Davis P, Kirkland KH, Mulloy KB. A model for physician education and consultation in pediatric environmental health—the Pediatric Environmental Health Specialty Units (PEHSU) program. Pediatr Clin North Am. 2007;54:1-13.

Although acute otitis media (AOM) has decreased in number, and especially the more severe difficult to treat versions, I was reminded that this still is a problem for young children based on personal experience with grandchildren. What can be baffling to some families is the fact that some strains of the same organism species cause AOM and some simply colonize the nasopharynx (NP) of children without causing any disease at all. These organisms include Streptococcus pneumoniae (SPN) and nontypeable Haemophilus influenzae (ntHi).

Recent studies have uncovered several molecular reasons for the pathogen vs. colonizer dichotomy:

• Strains within a species can have variants of a gene that make them more disease producing.

• Some usually colonizing strains produce disease after acquiring new genes.

• Some strains have native genes with on-off switches that convert them from a colonizing to disease producing under selected circumstances.

• Molecular targets in the respiratory tract increase, allowing more dense colonization that increases chances of AOM.

Variant gene

J.R. Gilsdorf, MD, and his group at the University of Michigan,¹ Ann Arbor, recently showed that among the various high-molecular-weight molecules (HMW) produced by 170 ntHi from three different geographically diverse countries, one variant in particular (HMW-A) was more likely to be found in strains producing AOM than strains simply colonizing the nasopharynx. The protein product of this gene allows better adherence to respiratory epithelia. So more bacteria sticking in the NP near the eustachian tube opening make development of AOM more likely. Some call this the “more barbarians at the gate” phenomenon.

Gene acquisition

SPN inherently has a somewhat incomplete arginine synthesis pathway. Because arginine is essential for growth of SPN, S. pneumoniae utilizes some host factors to compensate; but this compensation is inefficient. However, SPN strains can acquire new genes – usually from other gram-positive organisms in their environment – by a process called conjugation.

One recently reported acquired gene set is that which completes functionality of SPN’s arginine synthesis pathway.² Investigators showed that SPN that acquire these arginine synthesis genes replicate more readily in bodily fluids, such as serum or cerebrospinal fluid, making these strains more aggressive, more virulent, and more likely to produce disease. More efficient replication makes it very difficult for host immune responses to handle these SPN. This is not limited to AOM alone, but seems important in invasive disease (such as meningitis) from SPN type 7, which had recently become more frequent after introduction of pneumococcal conjugate vaccines.

On-off gene switches

Another group of investigators reported that a thing called “phasevarion,” which is fancy lingo for an on-off switch is at the root of more virulence in ntHi.³ It seems that some strains of ntHi have a version of the ModA2 gene, which is always turned off, while other strains have a gene that is always on. Then, there is a third version in which the gene is usually off, but turns on when in places like the middle ear. The ModA2 gene appears to affect several other downstream protein groups that include HMW-A, antibiotic susceptibility, and biofilm formation. When inoculated into the middle ear in a chinchilla AOM model, the ntHi strains that can turn on their ModA2 gene were much more likely to produce AOM than either version that could not change. Interestingly, the authors postulate that preventing the switch capability could be a novel way to prevent ntHi disease, such as pediatric AOM, acute bacterial sinusitis, or some bronchitis in adults.

Molecular environment becomes more favorable

Another group⁴ reported that adherence receptor for ntHi is intercellular adhesion molecule 1 (ICAM1), a molecule found in modest quantities on respiratory epithelium. You may know it as the attachment molecule for rhinovirus and enteroviruses. What makes this interesting is that adenovirus, respiratory syncytial virus, and exposure to cigarette smoke⁵ markedly increase expression of ICAM1 on respiratory epithelium, predisposing to more ntHi adhering and more likely to produce an inflammatory process, such as AOM. This is another version of the barbarians at the gate phenomenon.

So when families ask why SPN or ntHi sometimes exist quietly (colonize) the nasopharynx and sometimes they cause AOM or acute bacterial sinusitis, you can hopefully use these four examples as partial explanations of why the same bacterial species has strains that can be either colonizers or pathogens.

References

1. Infect Genet Evol. 2014 Dec;28:223-32

2. J Infect Dis. 2014 Jun 1;209:1781-91.

3. J Infect Dis. 2016 Jun 10. pii: jiw243. [Epub ahead of print]

4. Cell Microbiol. 2016 Feb 9. doi: 10.1111/cmi.12575. [Epub ahead of print]

5. Am J Respir Cell Mol Biol. 2003 Oct;29:472-82.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

Although acute otitis media (AOM) has decreased in number, and especially the more severe difficult to treat versions, I was reminded that this still is a problem for young children based on personal experience with grandchildren. What can be baffling to some families is the fact that some strains of the same organism species cause AOM and some simply colonize the nasopharynx (NP) of children without causing any disease at all. These organisms include Streptococcus pneumoniae (SPN) and nontypeable Haemophilus influenzae (ntHi).

Recent studies have uncovered several molecular reasons for the pathogen vs. colonizer dichotomy:

• Strains within a species can have variants of a gene that make them more disease producing.

• Some usually colonizing strains produce disease after acquiring new genes.

• Some strains have native genes with on-off switches that convert them from a colonizing to disease producing under selected circumstances.

• Molecular targets in the respiratory tract increase, allowing more dense colonization that increases chances of AOM.

Variant gene

J.R. Gilsdorf, MD, and his group at the University of Michigan,¹ Ann Arbor, recently showed that among the various high-molecular-weight molecules (HMW) produced by 170 ntHi from three different geographically diverse countries, one variant in particular (HMW-A) was more likely to be found in strains producing AOM than strains simply colonizing the nasopharynx. The protein product of this gene allows better adherence to respiratory epithelia. So more bacteria sticking in the NP near the eustachian tube opening make development of AOM more likely. Some call this the “more barbarians at the gate” phenomenon.

Gene acquisition

SPN inherently has a somewhat incomplete arginine synthesis pathway. Because arginine is essential for growth of SPN, S. pneumoniae utilizes some host factors to compensate; but this compensation is inefficient. However, SPN strains can acquire new genes – usually from other gram-positive organisms in their environment – by a process called conjugation.

One recently reported acquired gene set is that which completes functionality of SPN’s arginine synthesis pathway.² Investigators showed that SPN that acquire these arginine synthesis genes replicate more readily in bodily fluids, such as serum or cerebrospinal fluid, making these strains more aggressive, more virulent, and more likely to produce disease. More efficient replication makes it very difficult for host immune responses to handle these SPN. This is not limited to AOM alone, but seems important in invasive disease (such as meningitis) from SPN type 7, which had recently become more frequent after introduction of pneumococcal conjugate vaccines.

On-off gene switches

Another group of investigators reported that a thing called “phasevarion,” which is fancy lingo for an on-off switch is at the root of more virulence in ntHi.³ It seems that some strains of ntHi have a version of the ModA2 gene, which is always turned off, while other strains have a gene that is always on. Then, there is a third version in which the gene is usually off, but turns on when in places like the middle ear. The ModA2 gene appears to affect several other downstream protein groups that include HMW-A, antibiotic susceptibility, and biofilm formation. When inoculated into the middle ear in a chinchilla AOM model, the ntHi strains that can turn on their ModA2 gene were much more likely to produce AOM than either version that could not change. Interestingly, the authors postulate that preventing the switch capability could be a novel way to prevent ntHi disease, such as pediatric AOM, acute bacterial sinusitis, or some bronchitis in adults.

Molecular environment becomes more favorable

Another group⁴ reported that adherence receptor for ntHi is intercellular adhesion molecule 1 (ICAM1), a molecule found in modest quantities on respiratory epithelium. You may know it as the attachment molecule for rhinovirus and enteroviruses. What makes this interesting is that adenovirus, respiratory syncytial virus, and exposure to cigarette smoke⁵ markedly increase expression of ICAM1 on respiratory epithelium, predisposing to more ntHi adhering and more likely to produce an inflammatory process, such as AOM. This is another version of the barbarians at the gate phenomenon.

So when families ask why SPN or ntHi sometimes exist quietly (colonize) the nasopharynx and sometimes they cause AOM or acute bacterial sinusitis, you can hopefully use these four examples as partial explanations of why the same bacterial species has strains that can be either colonizers or pathogens.

References

1. Infect Genet Evol. 2014 Dec;28:223-32

2. J Infect Dis. 2014 Jun 1;209:1781-91.

3. J Infect Dis. 2016 Jun 10. pii: jiw243. [Epub ahead of print]

4. Cell Microbiol. 2016 Feb 9. doi: 10.1111/cmi.12575. [Epub ahead of print]

5. Am J Respir Cell Mol Biol. 2003 Oct;29:472-82.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

Although acute otitis media (AOM) has decreased in number, and especially the more severe difficult to treat versions, I was reminded that this still is a problem for young children based on personal experience with grandchildren. What can be baffling to some families is the fact that some strains of the same organism species cause AOM and some simply colonize the nasopharynx (NP) of children without causing any disease at all. These organisms include Streptococcus pneumoniae (SPN) and nontypeable Haemophilus influenzae (ntHi).

Recent studies have uncovered several molecular reasons for the pathogen vs. colonizer dichotomy:

• Strains within a species can have variants of a gene that make them more disease producing.

• Some usually colonizing strains produce disease after acquiring new genes.

• Some strains have native genes with on-off switches that convert them from a colonizing to disease producing under selected circumstances.

• Molecular targets in the respiratory tract increase, allowing more dense colonization that increases chances of AOM.

Variant gene

J.R. Gilsdorf, MD, and his group at the University of Michigan,¹ Ann Arbor, recently showed that among the various high-molecular-weight molecules (HMW) produced by 170 ntHi from three different geographically diverse countries, one variant in particular (HMW-A) was more likely to be found in strains producing AOM than strains simply colonizing the nasopharynx. The protein product of this gene allows better adherence to respiratory epithelia. So more bacteria sticking in the NP near the eustachian tube opening make development of AOM more likely. Some call this the “more barbarians at the gate” phenomenon.

Gene acquisition

SPN inherently has a somewhat incomplete arginine synthesis pathway. Because arginine is essential for growth of SPN, S. pneumoniae utilizes some host factors to compensate; but this compensation is inefficient. However, SPN strains can acquire new genes – usually from other gram-positive organisms in their environment – by a process called conjugation.

One recently reported acquired gene set is that which completes functionality of SPN’s arginine synthesis pathway.² Investigators showed that SPN that acquire these arginine synthesis genes replicate more readily in bodily fluids, such as serum or cerebrospinal fluid, making these strains more aggressive, more virulent, and more likely to produce disease. More efficient replication makes it very difficult for host immune responses to handle these SPN. This is not limited to AOM alone, but seems important in invasive disease (such as meningitis) from SPN type 7, which had recently become more frequent after introduction of pneumococcal conjugate vaccines.

On-off gene switches

Another group of investigators reported that a thing called “phasevarion,” which is fancy lingo for an on-off switch is at the root of more virulence in ntHi.³ It seems that some strains of ntHi have a version of the ModA2 gene, which is always turned off, while other strains have a gene that is always on. Then, there is a third version in which the gene is usually off, but turns on when in places like the middle ear. The ModA2 gene appears to affect several other downstream protein groups that include HMW-A, antibiotic susceptibility, and biofilm formation. When inoculated into the middle ear in a chinchilla AOM model, the ntHi strains that can turn on their ModA2 gene were much more likely to produce AOM than either version that could not change. Interestingly, the authors postulate that preventing the switch capability could be a novel way to prevent ntHi disease, such as pediatric AOM, acute bacterial sinusitis, or some bronchitis in adults.

Molecular environment becomes more favorable

Another group⁴ reported that adherence receptor for ntHi is intercellular adhesion molecule 1 (ICAM1), a molecule found in modest quantities on respiratory epithelium. You may know it as the attachment molecule for rhinovirus and enteroviruses. What makes this interesting is that adenovirus, respiratory syncytial virus, and exposure to cigarette smoke⁵ markedly increase expression of ICAM1 on respiratory epithelium, predisposing to more ntHi adhering and more likely to produce an inflammatory process, such as AOM. This is another version of the barbarians at the gate phenomenon.

So when families ask why SPN or ntHi sometimes exist quietly (colonize) the nasopharynx and sometimes they cause AOM or acute bacterial sinusitis, you can hopefully use these four examples as partial explanations of why the same bacterial species has strains that can be either colonizers or pathogens.

References

1. Infect Genet Evol. 2014 Dec;28:223-32

2. J Infect Dis. 2014 Jun 1;209:1781-91.

3. J Infect Dis. 2016 Jun 10. pii: jiw243. [Epub ahead of print]

4. Cell Microbiol. 2016 Feb 9. doi: 10.1111/cmi.12575. [Epub ahead of print]

5. Am J Respir Cell Mol Biol. 2003 Oct;29:472-82.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

I get the occasional heartfelt thank you note from a patient. I also get hate mail, but fortunately the thank yous predominate.

I still have all of them, going back to residency, in an old Nike box. They sit in a closet at home, taken out here and there – on bad days.

You know what I mean. The days where you screwed up, or had an angry patient get on your nerves and/or in your face. Where the schedule was accidentally double booked and you were running behind from the start. When you question your abilities and wonder why you still do this to yourself.

At the end of those days, I go home, dig out the box, and quietly read a few of the notes. Their neatly folded pages of gratitude remind me why I’m here, why I chose this path, why I need to be clear and ready for the patients depending on me the next day. They help me realize that there’s more good than bad in this job; that an unhappy, albeit vocal, few don’t represent most patients; and that I really do know what I’m doing, regardless of what Mr. I’m-going-to-complain-about-you-on-Yelp says.

Of course, there are other reminders of what you have to be thankful for, like families and dogs. But sometimes you need a reminder directly from the people you make a difference for every day, to let you know that this isn’t just a job. It’s why you once volunteered at a hospital, fought through organic chemistry, wrote out 20 (or more) drafts of a personal statement and studied for the MCAT. Because, once upon a time, this job was just a dream.

I don’t spend a lot of time with the notes – maybe 10 minutes reading a randomly pulled handful – but it’s enough to get me out of a funk. Then the old shoe box is carefully returned to my closet. Until I need it again.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I get the occasional heartfelt thank you note from a patient. I also get hate mail, but fortunately the thank yous predominate.

I still have all of them, going back to residency, in an old Nike box. They sit in a closet at home, taken out here and there – on bad days.

You know what I mean. The days where you screwed up, or had an angry patient get on your nerves and/or in your face. Where the schedule was accidentally double booked and you were running behind from the start. When you question your abilities and wonder why you still do this to yourself.

At the end of those days, I go home, dig out the box, and quietly read a few of the notes. Their neatly folded pages of gratitude remind me why I’m here, why I chose this path, why I need to be clear and ready for the patients depending on me the next day. They help me realize that there’s more good than bad in this job; that an unhappy, albeit vocal, few don’t represent most patients; and that I really do know what I’m doing, regardless of what Mr. I’m-going-to-complain-about-you-on-Yelp says.

Of course, there are other reminders of what you have to be thankful for, like families and dogs. But sometimes you need a reminder directly from the people you make a difference for every day, to let you know that this isn’t just a job. It’s why you once volunteered at a hospital, fought through organic chemistry, wrote out 20 (or more) drafts of a personal statement and studied for the MCAT. Because, once upon a time, this job was just a dream.

I don’t spend a lot of time with the notes – maybe 10 minutes reading a randomly pulled handful – but it’s enough to get me out of a funk. Then the old shoe box is carefully returned to my closet. Until I need it again.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I get the occasional heartfelt thank you note from a patient. I also get hate mail, but fortunately the thank yous predominate.

I still have all of them, going back to residency, in an old Nike box. They sit in a closet at home, taken out here and there – on bad days.

You know what I mean. The days where you screwed up, or had an angry patient get on your nerves and/or in your face. Where the schedule was accidentally double booked and you were running behind from the start. When you question your abilities and wonder why you still do this to yourself.

At the end of those days, I go home, dig out the box, and quietly read a few of the notes. Their neatly folded pages of gratitude remind me why I’m here, why I chose this path, why I need to be clear and ready for the patients depending on me the next day. They help me realize that there’s more good than bad in this job; that an unhappy, albeit vocal, few don’t represent most patients; and that I really do know what I’m doing, regardless of what Mr. I’m-going-to-complain-about-you-on-Yelp says.

Of course, there are other reminders of what you have to be thankful for, like families and dogs. But sometimes you need a reminder directly from the people you make a difference for every day, to let you know that this isn’t just a job. It’s why you once volunteered at a hospital, fought through organic chemistry, wrote out 20 (or more) drafts of a personal statement and studied for the MCAT. Because, once upon a time, this job was just a dream.

I don’t spend a lot of time with the notes – maybe 10 minutes reading a randomly pulled handful – but it’s enough to get me out of a funk. Then the old shoe box is carefully returned to my closet. Until I need it again.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.