Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

WASHINGTON – The oral Janus kinase inhibitor tofacitinib is safe and effective in patients with active psoriatic arthritis and an inadequate response to tumor necrosis factor inhibitors, according to findings from the phase III OPAL Beyond trial.

Both the American College of Rheumatology 20% improvement criteria (ACR20) response rate and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) scores at month 3 – the primary endpoints of the study – were superior with tofacitinib (Xeljanz) versus placebo in the 6-month, double-blind, randomized, multicenter trial, Dafna D. Gladman, MD, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

WASHINGTON – The oral Janus kinase inhibitor tofacitinib is safe and effective in patients with active psoriatic arthritis and an inadequate response to tumor necrosis factor inhibitors, according to findings from the phase III OPAL Beyond trial.

Both the American College of Rheumatology 20% improvement criteria (ACR20) response rate and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) scores at month 3 – the primary endpoints of the study – were superior with tofacitinib (Xeljanz) versus placebo in the 6-month, double-blind, randomized, multicenter trial, Dafna D. Gladman, MD, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

WASHINGTON – The oral Janus kinase inhibitor tofacitinib is safe and effective in patients with active psoriatic arthritis and an inadequate response to tumor necrosis factor inhibitors, according to findings from the phase III OPAL Beyond trial.

Both the American College of Rheumatology 20% improvement criteria (ACR20) response rate and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) scores at month 3 – the primary endpoints of the study – were superior with tofacitinib (Xeljanz) versus placebo in the 6-month, double-blind, randomized, multicenter trial, Dafna D. Gladman, MD, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

Acute kidney injury is common in children and young adults admitted to ICUs, and cannot always be identified by plasma creatinine level alone, according to the authors of a study presented at the meeting sponsored by the American Society of Nephrology.

The Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) study was a prospective, international, observational study in 4,683 patients aged 3 months to 25 years, recruited from 32 pediatric ICUs over the course of 3 months.

Hemera Technologies/Thinkstock

Acute kidney injury is common in children and young adults admitted to ICUs, and cannot always be identified by plasma creatinine level alone, according to the authors of a study presented at the meeting sponsored by the American Society of Nephrology.

The Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) study was a prospective, international, observational study in 4,683 patients aged 3 months to 25 years, recruited from 32 pediatric ICUs over the course of 3 months.

Hemera Technologies/Thinkstock

Acute kidney injury is common in children and young adults admitted to ICUs, and cannot always be identified by plasma creatinine level alone, according to the authors of a study presented at the meeting sponsored by the American Society of Nephrology.

The Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) study was a prospective, international, observational study in 4,683 patients aged 3 months to 25 years, recruited from 32 pediatric ICUs over the course of 3 months.

Hemera Technologies/Thinkstock

CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.

Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.

When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).

The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.

WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.

If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.

Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.

“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”

In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.

In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.

Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.

Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.

Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.

The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.

However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.

For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.

Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.

The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.

Dr. O’Gara reported no relevant disclosures.

[email protected]
On Twitter @karioakes

CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.

Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.

When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).

The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.

WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.

If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.

Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.

“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”

In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.

In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.

Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.

Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.

Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.

The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.

However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.

For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.

Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.

The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.

Dr. O’Gara reported no relevant disclosures.

[email protected]
On Twitter @karioakes

CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.

Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.

When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).

The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.

WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.

If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.

Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.

“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”

In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.

In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.

Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.

Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.

Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.

The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.

However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.

For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.

Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.

The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.

Dr. O’Gara reported no relevant disclosures.

[email protected]
On Twitter @karioakes

The American Society for Radiation Oncology has issued new guidelines recommending accelerated partial breast irradiation brachytherapy (APBI) as an alternative to whole breast irradiation (WBI) after surgery in early-stage breast cancer patients, and lowering the age range of patients considered suitable for the procedure to people 50 and older, from 60.

With APBI, localized radiation is delivered to the region around the excised tissue, reducing treatment time and sparing healthy tissue. APBI may also be considered for patients 40 and older, according to ASTRO, if they meet all of the pathologic criteria for suitability listed in the guidelines for patients 50 and above.

The guidelines represent the first ASTRO update on APBI since 2009. In addition to expanding the age range for APBI treatment, the guidelines add low-risk ductal carcinoma in situ as an indication. The guidelines also address intraoperative radiation therapy, or IORT, in which patients receive low-energy photon or electron radiation during surgery (Pract Rad Oncol. 2016 Nov. 17 doi: 10.1016/j.prro.2016.09.007).

While IORT is suitable for patients with invasive cancer eligible for APBI, the guidelines say, patients considering this option should be counseled about the risk of recurrence compared with standard treatment, and, with photon IORT, about potential toxicity risk requiring follow-up. Though more than 40 studies were considered by the ASTRO committee, including large randomized trials comparing APBI with WBI, the new recommendations represent “more of a tweak than a revolution,” said Jay Harris, MD, of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, one of the guideline authors.

Dr. Harris noted in an interview that two important randomized controlled trials comparing APBI and WBI are still underway, with full follow-up results expected in 2-3 years, after which more definitive recommendations can be made. For the intraoperative radiation advice contained in the guidelines, “we had evidence from two trials looking at different approaches,” Dr. Harris said. “One has long-term data using an electron beam in the operating room – this group showed that that approach seems reasonable in patients that we at ASTRO considered suitable in general for APBI. The other approach is low-dose photon radiation, for which we have only short-term follow-up, making us more hesitant to endorse it.” As for the new recommendation sanctioning APBI for ductal carcinoma, “There’s a lot of variation [in protocols] across the country, compared with invasive cancer,” Dr. Harris said. “We’re kind of all over the map with DCIS. This guideline presents another option.”

The guidelines were sponsored by ASTRO; two authors disclosed financial relationships with firms that make radiologic technology.

The American Society for Radiation Oncology has issued new guidelines recommending accelerated partial breast irradiation brachytherapy (APBI) as an alternative to whole breast irradiation (WBI) after surgery in early-stage breast cancer patients, and lowering the age range of patients considered suitable for the procedure to people 50 and older, from 60.

With APBI, localized radiation is delivered to the region around the excised tissue, reducing treatment time and sparing healthy tissue. APBI may also be considered for patients 40 and older, according to ASTRO, if they meet all of the pathologic criteria for suitability listed in the guidelines for patients 50 and above.

The guidelines represent the first ASTRO update on APBI since 2009. In addition to expanding the age range for APBI treatment, the guidelines add low-risk ductal carcinoma in situ as an indication. The guidelines also address intraoperative radiation therapy, or IORT, in which patients receive low-energy photon or electron radiation during surgery (Pract Rad Oncol. 2016 Nov. 17 doi: 10.1016/j.prro.2016.09.007).

While IORT is suitable for patients with invasive cancer eligible for APBI, the guidelines say, patients considering this option should be counseled about the risk of recurrence compared with standard treatment, and, with photon IORT, about potential toxicity risk requiring follow-up. Though more than 40 studies were considered by the ASTRO committee, including large randomized trials comparing APBI with WBI, the new recommendations represent “more of a tweak than a revolution,” said Jay Harris, MD, of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, one of the guideline authors.

Dr. Harris noted in an interview that two important randomized controlled trials comparing APBI and WBI are still underway, with full follow-up results expected in 2-3 years, after which more definitive recommendations can be made. For the intraoperative radiation advice contained in the guidelines, “we had evidence from two trials looking at different approaches,” Dr. Harris said. “One has long-term data using an electron beam in the operating room – this group showed that that approach seems reasonable in patients that we at ASTRO considered suitable in general for APBI. The other approach is low-dose photon radiation, for which we have only short-term follow-up, making us more hesitant to endorse it.” As for the new recommendation sanctioning APBI for ductal carcinoma, “There’s a lot of variation [in protocols] across the country, compared with invasive cancer,” Dr. Harris said. “We’re kind of all over the map with DCIS. This guideline presents another option.”

The guidelines were sponsored by ASTRO; two authors disclosed financial relationships with firms that make radiologic technology.

The American Society for Radiation Oncology has issued new guidelines recommending accelerated partial breast irradiation brachytherapy (APBI) as an alternative to whole breast irradiation (WBI) after surgery in early-stage breast cancer patients, and lowering the age range of patients considered suitable for the procedure to people 50 and older, from 60.

With APBI, localized radiation is delivered to the region around the excised tissue, reducing treatment time and sparing healthy tissue. APBI may also be considered for patients 40 and older, according to ASTRO, if they meet all of the pathologic criteria for suitability listed in the guidelines for patients 50 and above.

The guidelines represent the first ASTRO update on APBI since 2009. In addition to expanding the age range for APBI treatment, the guidelines add low-risk ductal carcinoma in situ as an indication. The guidelines also address intraoperative radiation therapy, or IORT, in which patients receive low-energy photon or electron radiation during surgery (Pract Rad Oncol. 2016 Nov. 17 doi: 10.1016/j.prro.2016.09.007).

While IORT is suitable for patients with invasive cancer eligible for APBI, the guidelines say, patients considering this option should be counseled about the risk of recurrence compared with standard treatment, and, with photon IORT, about potential toxicity risk requiring follow-up. Though more than 40 studies were considered by the ASTRO committee, including large randomized trials comparing APBI with WBI, the new recommendations represent “more of a tweak than a revolution,” said Jay Harris, MD, of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, one of the guideline authors.

Dr. Harris noted in an interview that two important randomized controlled trials comparing APBI and WBI are still underway, with full follow-up results expected in 2-3 years, after which more definitive recommendations can be made. For the intraoperative radiation advice contained in the guidelines, “we had evidence from two trials looking at different approaches,” Dr. Harris said. “One has long-term data using an electron beam in the operating room – this group showed that that approach seems reasonable in patients that we at ASTRO considered suitable in general for APBI. The other approach is low-dose photon radiation, for which we have only short-term follow-up, making us more hesitant to endorse it.” As for the new recommendation sanctioning APBI for ductal carcinoma, “There’s a lot of variation [in protocols] across the country, compared with invasive cancer,” Dr. Harris said. “We’re kind of all over the map with DCIS. This guideline presents another option.”

The guidelines were sponsored by ASTRO; two authors disclosed financial relationships with firms that make radiologic technology.

In the 11 studies that have examined the incidence of leiomyosarcoma (LMS) since the 2014 communications by the US Food and Drug Administration (FDA),¹ Dr. Matthew Siedhoff and colleagues found that the cumulative LMS incidence in 318,006 women was 0.0017%, or approximately 1 in 600. This is according to data Dr. Seidhoff presented November 16, 2016, at the 45th annual AAGL Global Congress on MIGS.² This reported risk is smaller than the 1 in 350 cited by the FDA in its 2014 notice.¹ Dr. Seidhoff concluded that, particularly in women aged younger than 50 years, minimally invasive hysterectomy remains a safe option for the informed patient to consider.

Regardless of the incidence of unsuspected LMS found in the studies published since 2014, what have been the practice changes among gynecologic surgeons as a result of the FDA’s 2014 actions? Kerac N. Falk, MD, explored this question with his colleagues at the Icahn School of Medicine in New York, New York. He presented these findings to AAGL congress attendees on November 16 in Orlando, Florida.³ Notably, of 197 responders to a survey sent to members of the Society of Gynecologic Oncologists, 12.5% reported decreasing their use of power morcellation. A full 38.8% reported discontinuing altogether the use of a power morcellator.

One in 5 (20%) of gyn oncologists previously using power morcellation reported switching to laparotomy. Importantly, the drive for the switch was “driven by media, patient request, and the FDA rather than physician choice,” Falk said.

What if physicians, and patients, have another choice?

Here at the AAGL meeting, Olympus announced the FDA clearance, marketing, and initial training on its contained tissue extraction system—the PneumoLiner containment device and its accompanying laparoscopic PK Morcellator (FIGURE).

Both tools, FDA cleared in April and October 2016, respectively, provide low-risk, appropriate women with “an improved safety device,” said Jubilee Brown, MD, AAGL representative on power morcellation to the FDA and Associate Director of Gynecologic Oncology at the Levine Cancer Institute of the Carolinas HealthCare System in Charlotte, North Carolina.

“We have found at our institution that we have had to do more opens and minilaps on patients without the option for power morcellation, and this new device offers a way for us not to have to do that. Minimally invasive surgery stays truly minimally invasive surgery,” said Dr. Brown.

“Although I have a handful of patients who have chosen open surgery over minimally invasive surgery when MIS was appropriate, by and large most patients prefer the minimally invasive approach to surgery—especially when they learn that they have reduced risk for complications, blood loss, and pain; will be back to normal life faster; and will have less cosmetic incisions,” said Dr. Brown. “We all have tried workarounds, but for low-risk, appropriate patients under FDA guidelines, this new device by Olympus brings us back to minimally invasive options, and that is a good thing.”

How does the Olympus containment system work?

The PneumoLiner is the first containment device to receive FDA market clearance that is designed for use with certain laparoscopic morcellators to isolate uterine tissue that is not suspected to contain cancer.⁴

The containment bag and morcellator are not indicated for use in women with tissue that is known or suspected to contain malignancy; and should not be used for removal of uterine tissue containing suspected fibroids in patients who are peri- or post-menopausal, or candidates for en bloc tissue removal vaginally or via mini-laparotomy.⁴

When insufflated, the PneumoLiner bag allows for space and surgeon visibility throughout the power morcellation procedure while maintaining a barrier to the escape of fluids, cells, and tissue fragments. The bag creates a barrier between the targeted tissue and nontargeted abdominal contents, minimizing the risk of inadvertent damage to adjacent structures, says Olympus.⁴ See this video, which demonstrates the procedure.

Surgeon training on new device use is rigid, comprehensive, and not to be overlooked

“This is one of the rare times in my career when, right out of the gate, we have a very rigid and comprehensive way of educating and training physicians on the proper utilization of a new technology (avoiding the cart-before-the-horse phenomenon, in which a clinician is given the tools without the proper education),” said AAGL immediate past president Arnold Advincula, MD, “and it is important to underscore that.” Dr. Advincula is the Levine Family Professor, Vice-Chair of Women’s Health, and Chief of Gynecology at Sloane Women’s Hospital, Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York.

Training plans

Instead of its sales force, Olympus is having surgeons train other surgeons. Clinical Education Specialists, a small, select group of individuals within the company, also will be able to train. The required training follows a rigid protocol that was validated and submitted to the FDA as part of the approval process, said Jerilyn Hitchings, Director of Procedure Marketing at Olympus. After training up to 40 surgeons in the past 3 weeks, Olympus expects to train another 100 at AAGL.

“We have strict criteria for training, including that they are advanced laparoscopists,” fulfilling a minimum number of surgeries within a 90-day period, said Hitchings.

The 1-hour training requires surgeons to perform a 4-step protocol and demonstrate unaided proficiency at training conclusion. Olympus will not sell its product to a facility until an advanced surgeon has been trained there, according to Hitchings. And many physicians are approaching their institutions inquiring about training now, she reports.

Applications for training will be submitted to the Olympus Professional Education Team for approval. “We want this to go well. We know that there are many physicians who are hoping that this becomes a good reality, and we want to make sure that it is done properly. The training process adheres to that agenda.”

Having the technology is step 1

OBG Management Board of Editors member Dr. Advincula struck an optimistic tone in his June 2016 Guest Editorial for the journal,⁶ indicating his belief that the “tissue morcellation pendulum,” which has swung toward non−minimally invasive approaches since 2014, can change direction. At the Olympus containment system official introduction event at AAGL, he expressed the same optimism:

“We now have technology that has the promise of being able to deliver to women a safe way to undergo tissue extraction, to undergo a minimally invasive surgical procedure. …When you combine innovation and education together, you ultimately are going to advance MIS worldwide. With all the things going on around the world today, I think it is important that women be able to have a choice, an autonomous choice with her physician. Having the technology that allows physicians to extract tissue safely, to give women the option of undergoing a minimally invasive surgery, is critically important. I look forward to seeing how we can continue to advance surgery. Partnership with clinicians and with industry, such as Olympus, is going to be key to the success of how we advance women’s health care in general.”

What do AAGL attendees have to say about it?

“It’s a good thing for the minimally invasive market,” said John B. Gebhart, MD, MS, vaginal hysterectomy representative at the star-studded Operating with the Stars event on Thursday, November 17, and Professor of Obstetrics and Gynecology at the Mayo Clinic in Rochester, Minnesota.

May Thomassee, MD, who practices in Lafayette, Louisiana, said that, for the past 3 years, she has been performing extracorporeal morcellation at her institution. “I think the new containment bag and morcellator devices that are attempting to be safer are a very good thing; however, my concern of introducing this new technology, such as bags, is that it may increase the cost within our health care system. We have had great success, and patients feel that they have options when we offer them—after informed consent and appropriate preoperative workup—an abdominal, vaginal, or extracorporeal morcellation approach.”

As a developer and proponent of the Extracorporeal Tissue Extraction (ExCITE) technique, Mireille Truong, MD, who demonstrated the ExCITE surgical approach with Dr. Advincula as part of the Research and Science Plenary here at AAGL, said, “I think the PneumoLiner is a great example of creativity and innovation. It’s good that we now have an FDA-approved device to offer and counsel patients as one of many options.” She added that, overall, the morcellation controversy has been “a positive experience. We have learned better as a community about how to approach new technology.”

In the 11 studies that have examined the incidence of leiomyosarcoma (LMS) since the 2014 communications by the US Food and Drug Administration (FDA),¹ Dr. Matthew Siedhoff and colleagues found that the cumulative LMS incidence in 318,006 women was 0.0017%, or approximately 1 in 600. This is according to data Dr. Seidhoff presented November 16, 2016, at the 45th annual AAGL Global Congress on MIGS.² This reported risk is smaller than the 1 in 350 cited by the FDA in its 2014 notice.¹ Dr. Seidhoff concluded that, particularly in women aged younger than 50 years, minimally invasive hysterectomy remains a safe option for the informed patient to consider.

Regardless of the incidence of unsuspected LMS found in the studies published since 2014, what have been the practice changes among gynecologic surgeons as a result of the FDA’s 2014 actions? Kerac N. Falk, MD, explored this question with his colleagues at the Icahn School of Medicine in New York, New York. He presented these findings to AAGL congress attendees on November 16 in Orlando, Florida.³ Notably, of 197 responders to a survey sent to members of the Society of Gynecologic Oncologists, 12.5% reported decreasing their use of power morcellation. A full 38.8% reported discontinuing altogether the use of a power morcellator.

One in 5 (20%) of gyn oncologists previously using power morcellation reported switching to laparotomy. Importantly, the drive for the switch was “driven by media, patient request, and the FDA rather than physician choice,” Falk said.

What if physicians, and patients, have another choice?

Here at the AAGL meeting, Olympus announced the FDA clearance, marketing, and initial training on its contained tissue extraction system—the PneumoLiner containment device and its accompanying laparoscopic PK Morcellator (FIGURE).

Both tools, FDA cleared in April and October 2016, respectively, provide low-risk, appropriate women with “an improved safety device,” said Jubilee Brown, MD, AAGL representative on power morcellation to the FDA and Associate Director of Gynecologic Oncology at the Levine Cancer Institute of the Carolinas HealthCare System in Charlotte, North Carolina.

“We have found at our institution that we have had to do more opens and minilaps on patients without the option for power morcellation, and this new device offers a way for us not to have to do that. Minimally invasive surgery stays truly minimally invasive surgery,” said Dr. Brown.

“Although I have a handful of patients who have chosen open surgery over minimally invasive surgery when MIS was appropriate, by and large most patients prefer the minimally invasive approach to surgery—especially when they learn that they have reduced risk for complications, blood loss, and pain; will be back to normal life faster; and will have less cosmetic incisions,” said Dr. Brown. “We all have tried workarounds, but for low-risk, appropriate patients under FDA guidelines, this new device by Olympus brings us back to minimally invasive options, and that is a good thing.”

How does the Olympus containment system work?

The PneumoLiner is the first containment device to receive FDA market clearance that is designed for use with certain laparoscopic morcellators to isolate uterine tissue that is not suspected to contain cancer.⁴

The containment bag and morcellator are not indicated for use in women with tissue that is known or suspected to contain malignancy; and should not be used for removal of uterine tissue containing suspected fibroids in patients who are peri- or post-menopausal, or candidates for en bloc tissue removal vaginally or via mini-laparotomy.⁴

When insufflated, the PneumoLiner bag allows for space and surgeon visibility throughout the power morcellation procedure while maintaining a barrier to the escape of fluids, cells, and tissue fragments. The bag creates a barrier between the targeted tissue and nontargeted abdominal contents, minimizing the risk of inadvertent damage to adjacent structures, says Olympus.⁴ See this video, which demonstrates the procedure.

Surgeon training on new device use is rigid, comprehensive, and not to be overlooked

“This is one of the rare times in my career when, right out of the gate, we have a very rigid and comprehensive way of educating and training physicians on the proper utilization of a new technology (avoiding the cart-before-the-horse phenomenon, in which a clinician is given the tools without the proper education),” said AAGL immediate past president Arnold Advincula, MD, “and it is important to underscore that.” Dr. Advincula is the Levine Family Professor, Vice-Chair of Women’s Health, and Chief of Gynecology at Sloane Women’s Hospital, Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York.

Training plans

Instead of its sales force, Olympus is having surgeons train other surgeons. Clinical Education Specialists, a small, select group of individuals within the company, also will be able to train. The required training follows a rigid protocol that was validated and submitted to the FDA as part of the approval process, said Jerilyn Hitchings, Director of Procedure Marketing at Olympus. After training up to 40 surgeons in the past 3 weeks, Olympus expects to train another 100 at AAGL.

“We have strict criteria for training, including that they are advanced laparoscopists,” fulfilling a minimum number of surgeries within a 90-day period, said Hitchings.

The 1-hour training requires surgeons to perform a 4-step protocol and demonstrate unaided proficiency at training conclusion. Olympus will not sell its product to a facility until an advanced surgeon has been trained there, according to Hitchings. And many physicians are approaching their institutions inquiring about training now, she reports.

Applications for training will be submitted to the Olympus Professional Education Team for approval. “We want this to go well. We know that there are many physicians who are hoping that this becomes a good reality, and we want to make sure that it is done properly. The training process adheres to that agenda.”

Having the technology is step 1

OBG Management Board of Editors member Dr. Advincula struck an optimistic tone in his June 2016 Guest Editorial for the journal,⁶ indicating his belief that the “tissue morcellation pendulum,” which has swung toward non−minimally invasive approaches since 2014, can change direction. At the Olympus containment system official introduction event at AAGL, he expressed the same optimism:

“We now have technology that has the promise of being able to deliver to women a safe way to undergo tissue extraction, to undergo a minimally invasive surgical procedure. …When you combine innovation and education together, you ultimately are going to advance MIS worldwide. With all the things going on around the world today, I think it is important that women be able to have a choice, an autonomous choice with her physician. Having the technology that allows physicians to extract tissue safely, to give women the option of undergoing a minimally invasive surgery, is critically important. I look forward to seeing how we can continue to advance surgery. Partnership with clinicians and with industry, such as Olympus, is going to be key to the success of how we advance women’s health care in general.”

What do AAGL attendees have to say about it?

“It’s a good thing for the minimally invasive market,” said John B. Gebhart, MD, MS, vaginal hysterectomy representative at the star-studded Operating with the Stars event on Thursday, November 17, and Professor of Obstetrics and Gynecology at the Mayo Clinic in Rochester, Minnesota.

May Thomassee, MD, who practices in Lafayette, Louisiana, said that, for the past 3 years, she has been performing extracorporeal morcellation at her institution. “I think the new containment bag and morcellator devices that are attempting to be safer are a very good thing; however, my concern of introducing this new technology, such as bags, is that it may increase the cost within our health care system. We have had great success, and patients feel that they have options when we offer them—after informed consent and appropriate preoperative workup—an abdominal, vaginal, or extracorporeal morcellation approach.”

As a developer and proponent of the Extracorporeal Tissue Extraction (ExCITE) technique, Mireille Truong, MD, who demonstrated the ExCITE surgical approach with Dr. Advincula as part of the Research and Science Plenary here at AAGL, said, “I think the PneumoLiner is a great example of creativity and innovation. It’s good that we now have an FDA-approved device to offer and counsel patients as one of many options.” She added that, overall, the morcellation controversy has been “a positive experience. We have learned better as a community about how to approach new technology.”

In the 11 studies that have examined the incidence of leiomyosarcoma (LMS) since the 2014 communications by the US Food and Drug Administration (FDA),¹ Dr. Matthew Siedhoff and colleagues found that the cumulative LMS incidence in 318,006 women was 0.0017%, or approximately 1 in 600. This is according to data Dr. Seidhoff presented November 16, 2016, at the 45th annual AAGL Global Congress on MIGS.² This reported risk is smaller than the 1 in 350 cited by the FDA in its 2014 notice.¹ Dr. Seidhoff concluded that, particularly in women aged younger than 50 years, minimally invasive hysterectomy remains a safe option for the informed patient to consider.

Regardless of the incidence of unsuspected LMS found in the studies published since 2014, what have been the practice changes among gynecologic surgeons as a result of the FDA’s 2014 actions? Kerac N. Falk, MD, explored this question with his colleagues at the Icahn School of Medicine in New York, New York. He presented these findings to AAGL congress attendees on November 16 in Orlando, Florida.³ Notably, of 197 responders to a survey sent to members of the Society of Gynecologic Oncologists, 12.5% reported decreasing their use of power morcellation. A full 38.8% reported discontinuing altogether the use of a power morcellator.

One in 5 (20%) of gyn oncologists previously using power morcellation reported switching to laparotomy. Importantly, the drive for the switch was “driven by media, patient request, and the FDA rather than physician choice,” Falk said.

What if physicians, and patients, have another choice?

Here at the AAGL meeting, Olympus announced the FDA clearance, marketing, and initial training on its contained tissue extraction system—the PneumoLiner containment device and its accompanying laparoscopic PK Morcellator (FIGURE).

Both tools, FDA cleared in April and October 2016, respectively, provide low-risk, appropriate women with “an improved safety device,” said Jubilee Brown, MD, AAGL representative on power morcellation to the FDA and Associate Director of Gynecologic Oncology at the Levine Cancer Institute of the Carolinas HealthCare System in Charlotte, North Carolina.

“We have found at our institution that we have had to do more opens and minilaps on patients without the option for power morcellation, and this new device offers a way for us not to have to do that. Minimally invasive surgery stays truly minimally invasive surgery,” said Dr. Brown.

“Although I have a handful of patients who have chosen open surgery over minimally invasive surgery when MIS was appropriate, by and large most patients prefer the minimally invasive approach to surgery—especially when they learn that they have reduced risk for complications, blood loss, and pain; will be back to normal life faster; and will have less cosmetic incisions,” said Dr. Brown. “We all have tried workarounds, but for low-risk, appropriate patients under FDA guidelines, this new device by Olympus brings us back to minimally invasive options, and that is a good thing.”

How does the Olympus containment system work?

The PneumoLiner is the first containment device to receive FDA market clearance that is designed for use with certain laparoscopic morcellators to isolate uterine tissue that is not suspected to contain cancer.⁴

The containment bag and morcellator are not indicated for use in women with tissue that is known or suspected to contain malignancy; and should not be used for removal of uterine tissue containing suspected fibroids in patients who are peri- or post-menopausal, or candidates for en bloc tissue removal vaginally or via mini-laparotomy.⁴

When insufflated, the PneumoLiner bag allows for space and surgeon visibility throughout the power morcellation procedure while maintaining a barrier to the escape of fluids, cells, and tissue fragments. The bag creates a barrier between the targeted tissue and nontargeted abdominal contents, minimizing the risk of inadvertent damage to adjacent structures, says Olympus.⁴ See this video, which demonstrates the procedure.

Surgeon training on new device use is rigid, comprehensive, and not to be overlooked

“This is one of the rare times in my career when, right out of the gate, we have a very rigid and comprehensive way of educating and training physicians on the proper utilization of a new technology (avoiding the cart-before-the-horse phenomenon, in which a clinician is given the tools without the proper education),” said AAGL immediate past president Arnold Advincula, MD, “and it is important to underscore that.” Dr. Advincula is the Levine Family Professor, Vice-Chair of Women’s Health, and Chief of Gynecology at Sloane Women’s Hospital, Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York.

Training plans

Instead of its sales force, Olympus is having surgeons train other surgeons. Clinical Education Specialists, a small, select group of individuals within the company, also will be able to train. The required training follows a rigid protocol that was validated and submitted to the FDA as part of the approval process, said Jerilyn Hitchings, Director of Procedure Marketing at Olympus. After training up to 40 surgeons in the past 3 weeks, Olympus expects to train another 100 at AAGL.

“We have strict criteria for training, including that they are advanced laparoscopists,” fulfilling a minimum number of surgeries within a 90-day period, said Hitchings.

The 1-hour training requires surgeons to perform a 4-step protocol and demonstrate unaided proficiency at training conclusion. Olympus will not sell its product to a facility until an advanced surgeon has been trained there, according to Hitchings. And many physicians are approaching their institutions inquiring about training now, she reports.

Applications for training will be submitted to the Olympus Professional Education Team for approval. “We want this to go well. We know that there are many physicians who are hoping that this becomes a good reality, and we want to make sure that it is done properly. The training process adheres to that agenda.”

Having the technology is step 1

OBG Management Board of Editors member Dr. Advincula struck an optimistic tone in his June 2016 Guest Editorial for the journal,⁶ indicating his belief that the “tissue morcellation pendulum,” which has swung toward non−minimally invasive approaches since 2014, can change direction. At the Olympus containment system official introduction event at AAGL, he expressed the same optimism:

“We now have technology that has the promise of being able to deliver to women a safe way to undergo tissue extraction, to undergo a minimally invasive surgical procedure. …When you combine innovation and education together, you ultimately are going to advance MIS worldwide. With all the things going on around the world today, I think it is important that women be able to have a choice, an autonomous choice with her physician. Having the technology that allows physicians to extract tissue safely, to give women the option of undergoing a minimally invasive surgery, is critically important. I look forward to seeing how we can continue to advance surgery. Partnership with clinicians and with industry, such as Olympus, is going to be key to the success of how we advance women’s health care in general.”

What do AAGL attendees have to say about it?

“It’s a good thing for the minimally invasive market,” said John B. Gebhart, MD, MS, vaginal hysterectomy representative at the star-studded Operating with the Stars event on Thursday, November 17, and Professor of Obstetrics and Gynecology at the Mayo Clinic in Rochester, Minnesota.

May Thomassee, MD, who practices in Lafayette, Louisiana, said that, for the past 3 years, she has been performing extracorporeal morcellation at her institution. “I think the new containment bag and morcellator devices that are attempting to be safer are a very good thing; however, my concern of introducing this new technology, such as bags, is that it may increase the cost within our health care system. We have had great success, and patients feel that they have options when we offer them—after informed consent and appropriate preoperative workup—an abdominal, vaginal, or extracorporeal morcellation approach.”

As a developer and proponent of the Extracorporeal Tissue Extraction (ExCITE) technique, Mireille Truong, MD, who demonstrated the ExCITE surgical approach with Dr. Advincula as part of the Research and Science Plenary here at AAGL, said, “I think the PneumoLiner is a great example of creativity and innovation. It’s good that we now have an FDA-approved device to offer and counsel patients as one of many options.” She added that, overall, the morcellation controversy has been “a positive experience. We have learned better as a community about how to approach new technology.”

BOSTON – Direct-acting antiretroviral therapies are safe and well tolerated in hepatitis C virus patients with comorbid psychiatric conditions, a study showed.

The finding that sustained virologic response (SVR) rates at 1 year were similar in genotype 1 HCV patients with and without psychiatric comorbidities could help end the stigma against treating this patient subgroup, stemming from when treatment with interferon risked psychiatric decompensation. That’s according to nurse practitioner Anne Moore, winner of this year’s Poster of Distinction Award at the American Association for the Study of Liver Diseases annual meeting.

Whitney McKnight/Frontline Medical News

[email protected]

On Twitter @whitneymcknight

BOSTON – Direct-acting antiretroviral therapies are safe and well tolerated in hepatitis C virus patients with comorbid psychiatric conditions, a study showed.

The finding that sustained virologic response (SVR) rates at 1 year were similar in genotype 1 HCV patients with and without psychiatric comorbidities could help end the stigma against treating this patient subgroup, stemming from when treatment with interferon risked psychiatric decompensation. That’s according to nurse practitioner Anne Moore, winner of this year’s Poster of Distinction Award at the American Association for the Study of Liver Diseases annual meeting.

Whitney McKnight/Frontline Medical News

[email protected]

On Twitter @whitneymcknight

BOSTON – Direct-acting antiretroviral therapies are safe and well tolerated in hepatitis C virus patients with comorbid psychiatric conditions, a study showed.

The finding that sustained virologic response (SVR) rates at 1 year were similar in genotype 1 HCV patients with and without psychiatric comorbidities could help end the stigma against treating this patient subgroup, stemming from when treatment with interferon risked psychiatric decompensation. That’s according to nurse practitioner Anne Moore, winner of this year’s Poster of Distinction Award at the American Association for the Study of Liver Diseases annual meeting.

Whitney McKnight/Frontline Medical News

[email protected]

On Twitter @whitneymcknight

Although patients have more assisted reproductive techniques (ART) available in recent years, management of infertility through minimally invasive surgical avenues can confront quality of life (QoL) and pathology concerns with birth rates equal to those with ART. This was a main takeaway in a packed ballroom in Orlando, Florida, at the 45th Global Congress of the AAGL. In this session, G. David Adamson, MD, brought together 3 top minimally invasive gynecologic surgeons to discuss clinical decisions in the overall and specific surgical management of: endometriomas and endometriosis, including deeply infiltrating disease; pelvic adhesions; distal tubal injury/occlusion; and proximal tubal occlusion by hysteroscopy.

Tommaso Falcone, MD, maintained that many patients (up to 85%) have pain with endometriomas, and addressing QoL for these women, with surgery versus managing their infertility only with in vitro fertilization (IVF), is an important consideration. Dr. Adamson noted that, “although there are no RCT data to guide management of endometriomas, we do have reasonable data to counsel patients on surgery versus IVF, with clinical considerations including patient age, presence of pain, and size of the endometrioma.”

Antonio Gargiulo, MD, advised attendees that when counseling patients on the role of laparoscopy in adhesiolysis to consider (1) that adhesions interfere with gamete and embryo transplant, (2) retrospective data from a small study show a positive effect of adhesiolysis in infertility, and (3) that the effect is dependent on the ASRM Adhesion Score. Regarding laparoscopy for distal tubal inclusion, he noted that case selection is important, as surgery can restore anatomic integrity but not functional integrity. In addition, he pointed out that neosalpingectomy before IVF should be considered in young women with mild hydrosalpinges when male factor infertility is present.

For proximal tubal occlusion, Dr. Gargiulo noted that hysteroscopy catheterization has diagnostic and therapeutic value, with contraindications including infection, inflammation, male factor infertility, and prior tubal surgery.

“Surgeons must offer and understand ART alternatives so that they can offer patient-centered choices,” said Dr. Gargiulo.

Finally, when does Dr. Leila Adamyan of the Federal State Institution Research Center for Obstetrics, Gynecology, and Perinatology of the V.I. Kulakov Russian Federation perform myomectomy before IVF? In the presence of:

• submucosal myoma
• myoma greater than 4 cm in size
• multiple myoma.

When sarcoma is suspected, she advises the use of endobags.

Although patients have more assisted reproductive techniques (ART) available in recent years, management of infertility through minimally invasive surgical avenues can confront quality of life (QoL) and pathology concerns with birth rates equal to those with ART. This was a main takeaway in a packed ballroom in Orlando, Florida, at the 45th Global Congress of the AAGL. In this session, G. David Adamson, MD, brought together 3 top minimally invasive gynecologic surgeons to discuss clinical decisions in the overall and specific surgical management of: endometriomas and endometriosis, including deeply infiltrating disease; pelvic adhesions; distal tubal injury/occlusion; and proximal tubal occlusion by hysteroscopy.

Tommaso Falcone, MD, maintained that many patients (up to 85%) have pain with endometriomas, and addressing QoL for these women, with surgery versus managing their infertility only with in vitro fertilization (IVF), is an important consideration. Dr. Adamson noted that, “although there are no RCT data to guide management of endometriomas, we do have reasonable data to counsel patients on surgery versus IVF, with clinical considerations including patient age, presence of pain, and size of the endometrioma.”

Antonio Gargiulo, MD, advised attendees that when counseling patients on the role of laparoscopy in adhesiolysis to consider (1) that adhesions interfere with gamete and embryo transplant, (2) retrospective data from a small study show a positive effect of adhesiolysis in infertility, and (3) that the effect is dependent on the ASRM Adhesion Score. Regarding laparoscopy for distal tubal inclusion, he noted that case selection is important, as surgery can restore anatomic integrity but not functional integrity. In addition, he pointed out that neosalpingectomy before IVF should be considered in young women with mild hydrosalpinges when male factor infertility is present.

For proximal tubal occlusion, Dr. Gargiulo noted that hysteroscopy catheterization has diagnostic and therapeutic value, with contraindications including infection, inflammation, male factor infertility, and prior tubal surgery.

“Surgeons must offer and understand ART alternatives so that they can offer patient-centered choices,” said Dr. Gargiulo.

Finally, when does Dr. Leila Adamyan of the Federal State Institution Research Center for Obstetrics, Gynecology, and Perinatology of the V.I. Kulakov Russian Federation perform myomectomy before IVF? In the presence of:

• submucosal myoma
• myoma greater than 4 cm in size
• multiple myoma.

When sarcoma is suspected, she advises the use of endobags.

Although patients have more assisted reproductive techniques (ART) available in recent years, management of infertility through minimally invasive surgical avenues can confront quality of life (QoL) and pathology concerns with birth rates equal to those with ART. This was a main takeaway in a packed ballroom in Orlando, Florida, at the 45th Global Congress of the AAGL. In this session, G. David Adamson, MD, brought together 3 top minimally invasive gynecologic surgeons to discuss clinical decisions in the overall and specific surgical management of: endometriomas and endometriosis, including deeply infiltrating disease; pelvic adhesions; distal tubal injury/occlusion; and proximal tubal occlusion by hysteroscopy.

Tommaso Falcone, MD, maintained that many patients (up to 85%) have pain with endometriomas, and addressing QoL for these women, with surgery versus managing their infertility only with in vitro fertilization (IVF), is an important consideration. Dr. Adamson noted that, “although there are no RCT data to guide management of endometriomas, we do have reasonable data to counsel patients on surgery versus IVF, with clinical considerations including patient age, presence of pain, and size of the endometrioma.”

Antonio Gargiulo, MD, advised attendees that when counseling patients on the role of laparoscopy in adhesiolysis to consider (1) that adhesions interfere with gamete and embryo transplant, (2) retrospective data from a small study show a positive effect of adhesiolysis in infertility, and (3) that the effect is dependent on the ASRM Adhesion Score. Regarding laparoscopy for distal tubal inclusion, he noted that case selection is important, as surgery can restore anatomic integrity but not functional integrity. In addition, he pointed out that neosalpingectomy before IVF should be considered in young women with mild hydrosalpinges when male factor infertility is present.

For proximal tubal occlusion, Dr. Gargiulo noted that hysteroscopy catheterization has diagnostic and therapeutic value, with contraindications including infection, inflammation, male factor infertility, and prior tubal surgery.

“Surgeons must offer and understand ART alternatives so that they can offer patient-centered choices,” said Dr. Gargiulo.

Finally, when does Dr. Leila Adamyan of the Federal State Institution Research Center for Obstetrics, Gynecology, and Perinatology of the V.I. Kulakov Russian Federation perform myomectomy before IVF? In the presence of:

• submucosal myoma
• myoma greater than 4 cm in size
• multiple myoma.

When sarcoma is suspected, she advises the use of endobags.

SAN FRANCISCO – You have a female patient come in with apparent breast development but no dark pubic hair – and she’s 7 years old. Is it a case of early puberty, a warning sign to test for possible conditions, or an unremarkable departure from typical development that does not require any intervention?

The answer to situations such as these varies, explained Dennis Styne, MD, professor of pediatrics, and Yocha Dehe Endowed Chair in Pediatric Endocrinology, at the University of California, Davis.

“We don’t know why puberty begins when it does even though we know many of the controlling factors,” Dr. Styne said at the annual meeting of the American Academy of Pediatrics, but it’s important to understand when “early” is so early that you should order lab evaluations, as opposed to simply letting an outlier’s body development continue as it would.

Normal puberty

Dr. Styne reviewed the Tanner stages of puberty for girls’ breast and pubic hair development and boys’ genital and pubic hair development, noting that the classic lower ages of pubertal onset are age 8 years in girls and 9 years in boys. Yet the normal curve may actually start earlier than those ages for U.S. girls, he noted. He shared the results of a 1997 Pediatrics study of 17,077 girls, in which by age 7 years, more than a quarter of black girls (27%) and 7% of white girls had reached at least Tanner stage 2. At age 8, nearly half of black girls (48%) and 15% of white girls had reached at least stage 2 (Pediatrics. 1997 Apr;99[4]:505-12).

Further, breast development, menarche, and early pubic hair development (pubarche) all occur earlier with increased body mass index, which has been increasing among children overall. Another study identified earlier breast development without increased body mass index: Stage 2 development occurred an average 10 months earlier in girls in 2006 than in 1991, regardless of BMI, even though no difference in LH or FSH levels occurred at these ages and estradiol level was even lower. The authors of that Danish study concluded some other factors besides pubertal hormones had to account for the increasingly earlier breast development in girls. Endocrine-disrupting chemicals are a possible cause.

Similarly, puberty in boys is occurring a bit earlier, but less dramatically so: A 2012 study of 4,131 boys found that 5.75% of black boys, 0.54% of white boys, and 1.16% of Hispanic boys had stage 2 pubic hair development by age 6. Meanwhile, 10.9% of black boys, 2% of white boys, and 2.5% of Hispanic boys began puberty with stage 2 pubic hair development at age 8 (Pediatrics 2012;130:e1058-68).

But the boys differ in one key way from the girls: Boys with obesity tend to begin puberty later than those with normal or overweight BMIs, even though overweight boys begin puberty earlier than those with normal weights.

This leaves age 8 years as a normal age to begin puberty in boys but leaves the ages for girls’ start less certain – perhaps 7 years for white girls and 6 years for black girls – but still controversial.

When to be concerned

Various neurotransmitters in the central nervous system control puberty by suppression during childhood, until a trigger for onset occurs that remains mysterious. But gene mutations, such as MKRN3 in girls, as well as brain tumors or trauma, can remove that disinhibition, prompting further investigation. Brain tumors causing precocious puberty are more common in boys than girls.

Rapid growth and bone age advancement, elevated serum levels of sex steroids, and breast development in girls could all indicate precocious puberty. If these signs are accompanied by a rise in gonadotropin values to pubertal levels, early central precocious puberty, which follows the normal course of puberty except that it is earlier, is likely.

With both sex steroids and gonadotropins in the pubertal range, a GnRH agonist could be used to control gonadal steroid production and stop bone age advancement, allowing children to reach a greater adult height if started before age 6 years. If the early puberty is slowly progressing and more subtle, no treatment at all may be necessary if there are no pathologic findings.

Without proper testing, however, a physician might as well be guessing at the cause of the early development.

“You need a highly sensitive assay, and you need pediatric standards, so you’ll probably have to send blood samples out to a national laboratory,” Dr. Styne said.

If sex hormones are being secreted at a higher rate with suppression of gonadotropins, the source is most likely autonomous secretion by the gonads or the adrenal glands.

“If you see a boy with precious puberty, with testes that are not as big as they should be for the pubertal testosterone levels, it could be that the source is the adrenal glands,” Dr. Styne said.

Meanwhile, about 75% of boys will have gynecomastia to some degree during puberty, likely because of a subtle early pubertal imbalance between estrogen and testosterone, Dr. Styne said. The condition usually regresses, but “if it doesn’t regress, there’s a chance scar tissue will develop and remain, leading to the need for surgical correction. Klinefelter syndrome must be ruled out in cases of gynecomastia or, alternatively, rarer cases of disorders of sexual development.

Dr. Styne reported that he had no relevant financial disclosures.

SAN FRANCISCO – You have a female patient come in with apparent breast development but no dark pubic hair – and she’s 7 years old. Is it a case of early puberty, a warning sign to test for possible conditions, or an unremarkable departure from typical development that does not require any intervention?

The answer to situations such as these varies, explained Dennis Styne, MD, professor of pediatrics, and Yocha Dehe Endowed Chair in Pediatric Endocrinology, at the University of California, Davis.

“We don’t know why puberty begins when it does even though we know many of the controlling factors,” Dr. Styne said at the annual meeting of the American Academy of Pediatrics, but it’s important to understand when “early” is so early that you should order lab evaluations, as opposed to simply letting an outlier’s body development continue as it would.

Normal puberty

Dr. Styne reviewed the Tanner stages of puberty for girls’ breast and pubic hair development and boys’ genital and pubic hair development, noting that the classic lower ages of pubertal onset are age 8 years in girls and 9 years in boys. Yet the normal curve may actually start earlier than those ages for U.S. girls, he noted. He shared the results of a 1997 Pediatrics study of 17,077 girls, in which by age 7 years, more than a quarter of black girls (27%) and 7% of white girls had reached at least Tanner stage 2. At age 8, nearly half of black girls (48%) and 15% of white girls had reached at least stage 2 (Pediatrics. 1997 Apr;99[4]:505-12).

Further, breast development, menarche, and early pubic hair development (pubarche) all occur earlier with increased body mass index, which has been increasing among children overall. Another study identified earlier breast development without increased body mass index: Stage 2 development occurred an average 10 months earlier in girls in 2006 than in 1991, regardless of BMI, even though no difference in LH or FSH levels occurred at these ages and estradiol level was even lower. The authors of that Danish study concluded some other factors besides pubertal hormones had to account for the increasingly earlier breast development in girls. Endocrine-disrupting chemicals are a possible cause.

Similarly, puberty in boys is occurring a bit earlier, but less dramatically so: A 2012 study of 4,131 boys found that 5.75% of black boys, 0.54% of white boys, and 1.16% of Hispanic boys had stage 2 pubic hair development by age 6. Meanwhile, 10.9% of black boys, 2% of white boys, and 2.5% of Hispanic boys began puberty with stage 2 pubic hair development at age 8 (Pediatrics 2012;130:e1058-68).

But the boys differ in one key way from the girls: Boys with obesity tend to begin puberty later than those with normal or overweight BMIs, even though overweight boys begin puberty earlier than those with normal weights.

This leaves age 8 years as a normal age to begin puberty in boys but leaves the ages for girls’ start less certain – perhaps 7 years for white girls and 6 years for black girls – but still controversial.

When to be concerned

Various neurotransmitters in the central nervous system control puberty by suppression during childhood, until a trigger for onset occurs that remains mysterious. But gene mutations, such as MKRN3 in girls, as well as brain tumors or trauma, can remove that disinhibition, prompting further investigation. Brain tumors causing precocious puberty are more common in boys than girls.

Rapid growth and bone age advancement, elevated serum levels of sex steroids, and breast development in girls could all indicate precocious puberty. If these signs are accompanied by a rise in gonadotropin values to pubertal levels, early central precocious puberty, which follows the normal course of puberty except that it is earlier, is likely.

With both sex steroids and gonadotropins in the pubertal range, a GnRH agonist could be used to control gonadal steroid production and stop bone age advancement, allowing children to reach a greater adult height if started before age 6 years. If the early puberty is slowly progressing and more subtle, no treatment at all may be necessary if there are no pathologic findings.

Without proper testing, however, a physician might as well be guessing at the cause of the early development.

“You need a highly sensitive assay, and you need pediatric standards, so you’ll probably have to send blood samples out to a national laboratory,” Dr. Styne said.

If sex hormones are being secreted at a higher rate with suppression of gonadotropins, the source is most likely autonomous secretion by the gonads or the adrenal glands.

“If you see a boy with precious puberty, with testes that are not as big as they should be for the pubertal testosterone levels, it could be that the source is the adrenal glands,” Dr. Styne said.

Meanwhile, about 75% of boys will have gynecomastia to some degree during puberty, likely because of a subtle early pubertal imbalance between estrogen and testosterone, Dr. Styne said. The condition usually regresses, but “if it doesn’t regress, there’s a chance scar tissue will develop and remain, leading to the need for surgical correction. Klinefelter syndrome must be ruled out in cases of gynecomastia or, alternatively, rarer cases of disorders of sexual development.

Dr. Styne reported that he had no relevant financial disclosures.

SAN FRANCISCO – You have a female patient come in with apparent breast development but no dark pubic hair – and she’s 7 years old. Is it a case of early puberty, a warning sign to test for possible conditions, or an unremarkable departure from typical development that does not require any intervention?

The answer to situations such as these varies, explained Dennis Styne, MD, professor of pediatrics, and Yocha Dehe Endowed Chair in Pediatric Endocrinology, at the University of California, Davis.

“We don’t know why puberty begins when it does even though we know many of the controlling factors,” Dr. Styne said at the annual meeting of the American Academy of Pediatrics, but it’s important to understand when “early” is so early that you should order lab evaluations, as opposed to simply letting an outlier’s body development continue as it would.

Normal puberty

Dr. Styne reviewed the Tanner stages of puberty for girls’ breast and pubic hair development and boys’ genital and pubic hair development, noting that the classic lower ages of pubertal onset are age 8 years in girls and 9 years in boys. Yet the normal curve may actually start earlier than those ages for U.S. girls, he noted. He shared the results of a 1997 Pediatrics study of 17,077 girls, in which by age 7 years, more than a quarter of black girls (27%) and 7% of white girls had reached at least Tanner stage 2. At age 8, nearly half of black girls (48%) and 15% of white girls had reached at least stage 2 (Pediatrics. 1997 Apr;99[4]:505-12).

Further, breast development, menarche, and early pubic hair development (pubarche) all occur earlier with increased body mass index, which has been increasing among children overall. Another study identified earlier breast development without increased body mass index: Stage 2 development occurred an average 10 months earlier in girls in 2006 than in 1991, regardless of BMI, even though no difference in LH or FSH levels occurred at these ages and estradiol level was even lower. The authors of that Danish study concluded some other factors besides pubertal hormones had to account for the increasingly earlier breast development in girls. Endocrine-disrupting chemicals are a possible cause.

Similarly, puberty in boys is occurring a bit earlier, but less dramatically so: A 2012 study of 4,131 boys found that 5.75% of black boys, 0.54% of white boys, and 1.16% of Hispanic boys had stage 2 pubic hair development by age 6. Meanwhile, 10.9% of black boys, 2% of white boys, and 2.5% of Hispanic boys began puberty with stage 2 pubic hair development at age 8 (Pediatrics 2012;130:e1058-68).

But the boys differ in one key way from the girls: Boys with obesity tend to begin puberty later than those with normal or overweight BMIs, even though overweight boys begin puberty earlier than those with normal weights.

This leaves age 8 years as a normal age to begin puberty in boys but leaves the ages for girls’ start less certain – perhaps 7 years for white girls and 6 years for black girls – but still controversial.

When to be concerned

Various neurotransmitters in the central nervous system control puberty by suppression during childhood, until a trigger for onset occurs that remains mysterious. But gene mutations, such as MKRN3 in girls, as well as brain tumors or trauma, can remove that disinhibition, prompting further investigation. Brain tumors causing precocious puberty are more common in boys than girls.

Rapid growth and bone age advancement, elevated serum levels of sex steroids, and breast development in girls could all indicate precocious puberty. If these signs are accompanied by a rise in gonadotropin values to pubertal levels, early central precocious puberty, which follows the normal course of puberty except that it is earlier, is likely.

With both sex steroids and gonadotropins in the pubertal range, a GnRH agonist could be used to control gonadal steroid production and stop bone age advancement, allowing children to reach a greater adult height if started before age 6 years. If the early puberty is slowly progressing and more subtle, no treatment at all may be necessary if there are no pathologic findings.

Without proper testing, however, a physician might as well be guessing at the cause of the early development.

“You need a highly sensitive assay, and you need pediatric standards, so you’ll probably have to send blood samples out to a national laboratory,” Dr. Styne said.

If sex hormones are being secreted at a higher rate with suppression of gonadotropins, the source is most likely autonomous secretion by the gonads or the adrenal glands.

“If you see a boy with precious puberty, with testes that are not as big as they should be for the pubertal testosterone levels, it could be that the source is the adrenal glands,” Dr. Styne said.

Meanwhile, about 75% of boys will have gynecomastia to some degree during puberty, likely because of a subtle early pubertal imbalance between estrogen and testosterone, Dr. Styne said. The condition usually regresses, but “if it doesn’t regress, there’s a chance scar tissue will develop and remain, leading to the need for surgical correction. Klinefelter syndrome must be ruled out in cases of gynecomastia or, alternatively, rarer cases of disorders of sexual development.

Dr. Styne reported that he had no relevant financial disclosures.

WASHINGTON – The investigational anti-interleukin-23 monoclonal antibody guselkumab was safe and well tolerated, and demonstrated significant improvement on a variety of measures in patients with active psoriatic arthritis in a randomized, placebo-controlled phase IIa study.

The primary endpoint of ACR20 at 24 weeks was achieved in 58% of 100 patients randomized to receive treatment with guselkumab versus 18.4% of 49 patients who received placebo, Atul A. Deodhar, MD, reported in a late-breaking abstract presentation at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

[email protected]

WASHINGTON – The investigational anti-interleukin-23 monoclonal antibody guselkumab was safe and well tolerated, and demonstrated significant improvement on a variety of measures in patients with active psoriatic arthritis in a randomized, placebo-controlled phase IIa study.

The primary endpoint of ACR20 at 24 weeks was achieved in 58% of 100 patients randomized to receive treatment with guselkumab versus 18.4% of 49 patients who received placebo, Atul A. Deodhar, MD, reported in a late-breaking abstract presentation at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

[email protected]

WASHINGTON – The investigational anti-interleukin-23 monoclonal antibody guselkumab was safe and well tolerated, and demonstrated significant improvement on a variety of measures in patients with active psoriatic arthritis in a randomized, placebo-controlled phase IIa study.

The primary endpoint of ACR20 at 24 weeks was achieved in 58% of 100 patients randomized to receive treatment with guselkumab versus 18.4% of 49 patients who received placebo, Atul A. Deodhar, MD, reported in a late-breaking abstract presentation at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

[email protected]