MIAMI BEACH – Two new antifungal agents on the market – luliconazole and naftifine – each have something unique to offer when it comes to treating tinea pedis, according to Dr. Boni E. Elewski.

Luliconazole is an azole drug, meaning it is broad spectrum and kills dermatophytes, yeast, and molds. Also, like all azoles, it has some antibacterial activity, she said at the South Beach Symposium.

Naftifine is an allylamine drug, and is mainly an antidermatophyte agent – albeit a “very, very potent antidermatophyte” – with no antibacterial activity, she said.

Both are approved for once-daily use for 2 weeks, and that’s good because the short treatment duration improves adherence to the regimen, especially compared with other drugs that require 4-6 weeks of treatment to eradicate the problem, noted Dr. Elewski, professor of dermatology and director of clinical trials research at the University of Alabama at Birmingham.

Both drugs also stay in the skin and continue working after treatment stops.

Making the choice regarding which drug or class of drugs to use depends on the patient’s symptoms.

“First of all, tinea pedis may not be obvious. People don’t often tell you, ‘This is what I have – it’s tinea pedis,’ ” she said.

Keep in mind that tinea pedis and onychomycosis are related. If you have a patient who you think has onychomycosis, look at the bottom of their foot, she advised.

“If they don’t have tinea pedis, they probably don’t have onychomycosis unless they’ve had tinea pedis recently and got rid of it,” she said.

Also, look for collarettes of scale, which may be very subtle and may look like “tiny little circular pieces of scale on the medial or lateral foot.”

“If you are not sure, just keep looking harder because you might see it,” Dr. Elewski said.

Interdigital tinea pedis will be a little more obvious, with scaling and crusting between the toes, as well as maceration and oozing in many cases.

When the toe web is oozing, you’re likely dealing with intertrigo, she said.

In such cases, an azole cream is the better treatment choice, because azoles will kill Candida, bacteria, and dermatophytes that are there, she said.

“So when I have a moist macerated space, I like an azole. If you have a dry scaly process – with or without the collarettes – you’re probably better with an allylamine, particularly if you use a keratolytic with it, something that has urea or a lactic acid,” she said.

Dr. Elewski is a consultant for Valeant Pharmaceuticals International and a contracted researcher for Anacor Pharmaceuticals.

MIAMI BEACH – Two new antifungal agents on the market – luliconazole and naftifine – each have something unique to offer when it comes to treating tinea pedis, according to Dr. Boni E. Elewski.

Luliconazole is an azole drug, meaning it is broad spectrum and kills dermatophytes, yeast, and molds. Also, like all azoles, it has some antibacterial activity, she said at the South Beach Symposium.

Naftifine is an allylamine drug, and is mainly an antidermatophyte agent – albeit a “very, very potent antidermatophyte” – with no antibacterial activity, she said.

Both are approved for once-daily use for 2 weeks, and that’s good because the short treatment duration improves adherence to the regimen, especially compared with other drugs that require 4-6 weeks of treatment to eradicate the problem, noted Dr. Elewski, professor of dermatology and director of clinical trials research at the University of Alabama at Birmingham.

Both drugs also stay in the skin and continue working after treatment stops.

Making the choice regarding which drug or class of drugs to use depends on the patient’s symptoms.

“First of all, tinea pedis may not be obvious. People don’t often tell you, ‘This is what I have – it’s tinea pedis,’ ” she said.

Keep in mind that tinea pedis and onychomycosis are related. If you have a patient who you think has onychomycosis, look at the bottom of their foot, she advised.

“If they don’t have tinea pedis, they probably don’t have onychomycosis unless they’ve had tinea pedis recently and got rid of it,” she said.

Also, look for collarettes of scale, which may be very subtle and may look like “tiny little circular pieces of scale on the medial or lateral foot.”

“If you are not sure, just keep looking harder because you might see it,” Dr. Elewski said.

Interdigital tinea pedis will be a little more obvious, with scaling and crusting between the toes, as well as maceration and oozing in many cases.

When the toe web is oozing, you’re likely dealing with intertrigo, she said.

In such cases, an azole cream is the better treatment choice, because azoles will kill Candida, bacteria, and dermatophytes that are there, she said.

“So when I have a moist macerated space, I like an azole. If you have a dry scaly process – with or without the collarettes – you’re probably better with an allylamine, particularly if you use a keratolytic with it, something that has urea or a lactic acid,” she said.

Dr. Elewski is a consultant for Valeant Pharmaceuticals International and a contracted researcher for Anacor Pharmaceuticals.

MIAMI BEACH – Two new antifungal agents on the market – luliconazole and naftifine – each have something unique to offer when it comes to treating tinea pedis, according to Dr. Boni E. Elewski.

Luliconazole is an azole drug, meaning it is broad spectrum and kills dermatophytes, yeast, and molds. Also, like all azoles, it has some antibacterial activity, she said at the South Beach Symposium.

Naftifine is an allylamine drug, and is mainly an antidermatophyte agent – albeit a “very, very potent antidermatophyte” – with no antibacterial activity, she said.

Both are approved for once-daily use for 2 weeks, and that’s good because the short treatment duration improves adherence to the regimen, especially compared with other drugs that require 4-6 weeks of treatment to eradicate the problem, noted Dr. Elewski, professor of dermatology and director of clinical trials research at the University of Alabama at Birmingham.

Both drugs also stay in the skin and continue working after treatment stops.

Making the choice regarding which drug or class of drugs to use depends on the patient’s symptoms.

“First of all, tinea pedis may not be obvious. People don’t often tell you, ‘This is what I have – it’s tinea pedis,’ ” she said.

Keep in mind that tinea pedis and onychomycosis are related. If you have a patient who you think has onychomycosis, look at the bottom of their foot, she advised.

“If they don’t have tinea pedis, they probably don’t have onychomycosis unless they’ve had tinea pedis recently and got rid of it,” she said.

Also, look for collarettes of scale, which may be very subtle and may look like “tiny little circular pieces of scale on the medial or lateral foot.”

“If you are not sure, just keep looking harder because you might see it,” Dr. Elewski said.

Interdigital tinea pedis will be a little more obvious, with scaling and crusting between the toes, as well as maceration and oozing in many cases.

When the toe web is oozing, you’re likely dealing with intertrigo, she said.

In such cases, an azole cream is the better treatment choice, because azoles will kill Candida, bacteria, and dermatophytes that are there, she said.

“So when I have a moist macerated space, I like an azole. If you have a dry scaly process – with or without the collarettes – you’re probably better with an allylamine, particularly if you use a keratolytic with it, something that has urea or a lactic acid,” she said.

Dr. Elewski is a consultant for Valeant Pharmaceuticals International and a contracted researcher for Anacor Pharmaceuticals.

SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.

The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.

“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.

Whitney McKnight/Frontline Medical News

“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”

Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.

Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.

Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.

While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.

The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.

Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”

[email protected]

On Twitter @whitneymcknight

SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.

The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.

“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.

Whitney McKnight/Frontline Medical News

“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”

Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.

Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.

Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.

While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.

The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.

Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”

[email protected]

On Twitter @whitneymcknight

SCOTTSDALE, ARIZ. – Acute renal failure occurred postoperatively in one-third of patients who underwent endograft explantation after endovascular abdominal aortic aneurysm repair (EVAR), according to the results of a small retrospective study.

The perioperative infected EVAR (I-EVAR) mortality across the study’s 36 patient records (83% male patients, average age 69 years), culled from four surgery centers’ data from 1997 to 2014, was 8%. The overall mortality was 25%, according to Dr. Victor J. Davila of Mayo Clinic Arizona, Phoenix, and his colleagues. Dr. Davila presented the findings at the Southern Association for Vascular Surgery annual meeting.

“These data show that I-EVAR explantation can be performed safely, with acceptable morbidity and mortality,” said Dr. Davila, who noted that while acceptable, the rates were still high, particularly for acute renal failure.

Whitney McKnight/Frontline Medical News

“We did not find any difference between the patients who developed renal failure and the type of graft, whether or not there was suprarenal fixation, and an incidence of postoperative acute renal failure,” Dr. Davila said, “However, because acute renal failure is multifactorial, we need to minimize aortic clamp time, as well as minimize the aortic intimal disruption around the renal arteries.”

Three deaths occurred within 30 days post operation, all from anastomotic dehiscence. Additional short-term morbidities included respiratory failure that required tracheostomy in three patients, and bleeding and sepsis in two patients each. Six patients required re-exploration because of infected hematoma, lymphatic leak, small-bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Six more deaths occurred at a mean follow-up of 402 days. One death was attributable to a ruptured aneurysm, another to a progressive inflammatory illness, and four deaths were of indeterminate cause.

Only three of the explantations reviewed by Dr. Davila and his colleagues were considered emergent. The rest (92%) were either elective or urgent. Infected patients tended to present with leukocytosis (63%), pain (58%), and fever (56%), usually about 65 days prior to explantation. The average time between EVAR and presentation with infection was 589 days.

Although most underwent total graft excision, two patients underwent partial excision, including one with a distal iliac limb infection that showed no sign of infection within the main portion of the endograft. Nearly three-quarters of patients had in situ reconstruction.

While nearly a third of patients had positive preoperative blood cultures indicating infection, 81% of intraoperative cultures taken from the explanted graft, aneurysm wall, or sac contents indicated infection.

The gram-positive Staphylococcus and Streptococcus were the most common organisms found in cultures (33% and 17%, respectively), although anaerobics were found in a third of patients, gram negatives in a quarter of patients, and fungal infections in 14%. A majority (58%) of patients received long-term suppressive antibiotic therapy.

Surgeons should reserve the option to keep a graft in situ only in infected EVAR patients who likely would not survive surgical explantation and reconstruction, Dr. Davila said. “Although I believe [medical management] is an alternative, the best course of action is to remove the endograft.”

[email protected]

On Twitter @whitneymcknight

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].