Photo by Juan D. Alfonso

Vela Diagnostics’ Sentosa® SX Cell-free DNA (cfDNA) Kit has received the CE-IVD mark, which means this kit is approved for in vitro diagnostics use in the European Union.

The Sentosa® SX cfDNA Kit is intended to extract free-circulating DNA from human plasma.

The kit was developed for use in next-generation sequencing and real-time polymerase chain reaction workflows.

The kit is designed to run on the Sentosa® SX101 instrument and works with whole blood samples collected in Cell-free DNA BCT from Streck, K2, or K3 EDTA tubes.

Automated sample extraction with the Sentosa® SX cfDNA Kit takes approximately 3.5 hours. It requires 20 minutes of operator hands-on time and 4 mL of plasma from the clinical sample.

The Sentosa® SX cfDNA Kit is able to recover low-frequency DNA variants in blood, according to Vela Diagnostics.

Results from a pilot study testing the kit were presented in a poster at the AMP 2016 Annual Meeting.

Photo by Juan D. Alfonso

Vela Diagnostics’ Sentosa® SX Cell-free DNA (cfDNA) Kit has received the CE-IVD mark, which means this kit is approved for in vitro diagnostics use in the European Union.

The Sentosa® SX cfDNA Kit is intended to extract free-circulating DNA from human plasma.

The kit was developed for use in next-generation sequencing and real-time polymerase chain reaction workflows.

The kit is designed to run on the Sentosa® SX101 instrument and works with whole blood samples collected in Cell-free DNA BCT from Streck, K2, or K3 EDTA tubes.

Automated sample extraction with the Sentosa® SX cfDNA Kit takes approximately 3.5 hours. It requires 20 minutes of operator hands-on time and 4 mL of plasma from the clinical sample.

The Sentosa® SX cfDNA Kit is able to recover low-frequency DNA variants in blood, according to Vela Diagnostics.

Results from a pilot study testing the kit were presented in a poster at the AMP 2016 Annual Meeting.

Photo by Juan D. Alfonso

Vela Diagnostics’ Sentosa® SX Cell-free DNA (cfDNA) Kit has received the CE-IVD mark, which means this kit is approved for in vitro diagnostics use in the European Union.

The Sentosa® SX cfDNA Kit is intended to extract free-circulating DNA from human plasma.

The kit was developed for use in next-generation sequencing and real-time polymerase chain reaction workflows.

The kit is designed to run on the Sentosa® SX101 instrument and works with whole blood samples collected in Cell-free DNA BCT from Streck, K2, or K3 EDTA tubes.

Automated sample extraction with the Sentosa® SX cfDNA Kit takes approximately 3.5 hours. It requires 20 minutes of operator hands-on time and 4 mL of plasma from the clinical sample.

The Sentosa® SX cfDNA Kit is able to recover low-frequency DNA variants in blood, according to Vela Diagnostics.

Results from a pilot study testing the kit were presented in a poster at the AMP 2016 Annual Meeting.

WASHINGTON – After a life-threatening event prompted a trial of continuous monitoring of patients during intracranial stereotactic electroencephalogram (EEG), the rate of adverse events and missed seizures went to zero, according to a single-center analysis presented at the annual meeting of the American Epilepsy Society.

“After initiating a full-time, bedside sitter, none of the major events we saw in the presitter period, which included unrecognized tonic-clonic seizures or patient removal of electrodes, was observed,” reported Brad Kamitaki, MD, who is completing an epilepsy fellowship at Columbia University, New York.

Ted Bosworth/Frontline Medical News

WASHINGTON – After a life-threatening event prompted a trial of continuous monitoring of patients during intracranial stereotactic electroencephalogram (EEG), the rate of adverse events and missed seizures went to zero, according to a single-center analysis presented at the annual meeting of the American Epilepsy Society.

“After initiating a full-time, bedside sitter, none of the major events we saw in the presitter period, which included unrecognized tonic-clonic seizures or patient removal of electrodes, was observed,” reported Brad Kamitaki, MD, who is completing an epilepsy fellowship at Columbia University, New York.

Ted Bosworth/Frontline Medical News

WASHINGTON – After a life-threatening event prompted a trial of continuous monitoring of patients during intracranial stereotactic electroencephalogram (EEG), the rate of adverse events and missed seizures went to zero, according to a single-center analysis presented at the annual meeting of the American Epilepsy Society.

“After initiating a full-time, bedside sitter, none of the major events we saw in the presitter period, which included unrecognized tonic-clonic seizures or patient removal of electrodes, was observed,” reported Brad Kamitaki, MD, who is completing an epilepsy fellowship at Columbia University, New York.

Ted Bosworth/Frontline Medical News

A woman with a transplanted uterus gave birth to a live baby boy in Dallas, the first birth from a transplanted uterus in the United States. It is also the first birth resulting from uterine transplantation to be performed outside of Sweden, where a total of eight births have occurred.

“This really confirms that this is doable, that it can be replicated,” said Giuliano Testa, MD, chief of abdominal transplantation at Baylor University Medical Center, Dallas, during a press conference to discuss the birth.

With time, Dr. Testa said in an interview, he foresees uterine transplantation becoming a realistic alternative for some women. “It’s a great solution for the woman who really wants to carry her own pregnancy.”

“This is the best of academic medicine,” Dr. Testa said of the international collaboration and transparency among investigators working in the nascent field. “The communication is constant; we learn from each other ... I am very excited about what will come in the future.”

In order to protect the privacy of the patient and her family, physicians did not disclose the patient’s name, location, or the exact date of the birth. The patient also did not wish to share the infant’s gestational age at birth or birth weight, or whether the uterus had been removed after the birth. Transplanted uteri are meant to be removed after one or two pregnancies, so the recipient doesn’t have to be on lifelong immunosuppression once the desired pregnancies have been achieved.

However, during the press conference, the surgical team shared that the mother is home and doing well, and the infant is on room air and feeding well. A video of the birth shown at the press conference showed a vernix-covered baby who began crying vigorously even before his feet were delivered during the cesarean delivery.

The transplantation, pregnancy via in vitro fertilization, and subsequent birth were accomplished as part of a 10-patient clinical trial of uterine transplantation at Baylor University Medical Center. Women aged 20-35 years with absolute uterine factor infertility, such as those with congenitally absent uteri, were eligible to participate. Donors must have had one full-term delivery and may be aged 30-65 years; menopause does not render a uterus incapable of carrying a pregnancy. Donors are able to retain their ovaries.

Another study participant at Baylor is late into her pregnancy as well, Dr. Testa said.

The extensive screening process for uterus donation ensures that the team is using “a good organ from a good donor,” said Liza Johannesson, MD, PhD. In an interview, she said that the harvest is now about a 4-5 hour open procedure that takes the uterus, the cervix, and the very superior portion of the vagina, as well as the uterine arteries and veins out to the internal iliac bilaterally. The utero-ovarian veins also are harvested.

To date, the six women who have been donors in the Baylor program have not had serious complications and have returned to their previous level of function, said Dr. Johannesson, who came to Baylor from Sahlgrenska University Hospital’s successful uterine transplantation team in Gothenburg, Sweden.

Internationally, investigators have been working to reduce morbidity for women who donate their uterus. Since the vascular tree of the uterus must also be dissected and preserved during the organ harvesting procedure, operative time is longer than for a simple hysterectomy, and there’s increased risk of urinary dysfunction because of the extensive dissection, Antonio R. Gargiulo, MD, said in an interview.*

Dr. Gargiulo, medical director of the center for robotic surgery at Brigham and Women’s Hospital, Boston, said that the first few uterine harvest procedures took much longer, up to 10 hours. But, he said, the vascular harvest “is well within the capability of the best gynecologic oncology surgeons,” and newer techniques may further reduce the donor morbidity.

Using the utero-ovarian vein as the primary outflow tract is “a promising modification of this operation” that may be the “technical key to making this procedure the least morbid possible,” said Dr. Gargiulo, a reproductive endocrinologist who is involved with the development of a uterine transplantation program at the Brigham and Women’s Hospital.

Dr. Johannesson said that the Baylor team currently dissects the entire uterine vascular tree and reanastomoses what vessels they can. She pointed out that even with the best imaging techniques, it can be difficult to ascertain the best vessels until the surgery’s actually being performed.

All of the surgeons interviewed emphasized that each procedure represents an opportunity for growth in a young field with a steep learning curve. They expect ongoing technical advances, including the use of robotic surgery, to reduce operative time and lessen morbidity.

It’s worth pressing on in this field for the sake of the patients, said Dr. Testa, speaking for his transplant team. “We are all humbled by the depth of the desire of a woman to carry her own pregnancy.”

Dr. Johannesson said that she hopes that today when gynecologists talk to teenage patients who have absolute uterine infertility, they will be offering a message of hope. “When they meet young women, they should tell them that they shouldn’t stop hoping,” she said. “There is hope that they will be able to carry their own pregnancy.”

Dr. Gargiulo has been a paid consultant for Kawasaki Robotics and OmniGuide. Dr. Testa and Dr. Johannesson reported that they had no relevant conflicts of interest.
 

*Correction, 12/12/17: The reason for the increased risk of urinary dysfunction was misstated.

[email protected]
On Twitter @karioakes

A woman with a transplanted uterus gave birth to a live baby boy in Dallas, the first birth from a transplanted uterus in the United States. It is also the first birth resulting from uterine transplantation to be performed outside of Sweden, where a total of eight births have occurred.

“This really confirms that this is doable, that it can be replicated,” said Giuliano Testa, MD, chief of abdominal transplantation at Baylor University Medical Center, Dallas, during a press conference to discuss the birth.

With time, Dr. Testa said in an interview, he foresees uterine transplantation becoming a realistic alternative for some women. “It’s a great solution for the woman who really wants to carry her own pregnancy.”

“This is the best of academic medicine,” Dr. Testa said of the international collaboration and transparency among investigators working in the nascent field. “The communication is constant; we learn from each other ... I am very excited about what will come in the future.”

In order to protect the privacy of the patient and her family, physicians did not disclose the patient’s name, location, or the exact date of the birth. The patient also did not wish to share the infant’s gestational age at birth or birth weight, or whether the uterus had been removed after the birth. Transplanted uteri are meant to be removed after one or two pregnancies, so the recipient doesn’t have to be on lifelong immunosuppression once the desired pregnancies have been achieved.

However, during the press conference, the surgical team shared that the mother is home and doing well, and the infant is on room air and feeding well. A video of the birth shown at the press conference showed a vernix-covered baby who began crying vigorously even before his feet were delivered during the cesarean delivery.

The transplantation, pregnancy via in vitro fertilization, and subsequent birth were accomplished as part of a 10-patient clinical trial of uterine transplantation at Baylor University Medical Center. Women aged 20-35 years with absolute uterine factor infertility, such as those with congenitally absent uteri, were eligible to participate. Donors must have had one full-term delivery and may be aged 30-65 years; menopause does not render a uterus incapable of carrying a pregnancy. Donors are able to retain their ovaries.

Another study participant at Baylor is late into her pregnancy as well, Dr. Testa said.

The extensive screening process for uterus donation ensures that the team is using “a good organ from a good donor,” said Liza Johannesson, MD, PhD. In an interview, she said that the harvest is now about a 4-5 hour open procedure that takes the uterus, the cervix, and the very superior portion of the vagina, as well as the uterine arteries and veins out to the internal iliac bilaterally. The utero-ovarian veins also are harvested.

To date, the six women who have been donors in the Baylor program have not had serious complications and have returned to their previous level of function, said Dr. Johannesson, who came to Baylor from Sahlgrenska University Hospital’s successful uterine transplantation team in Gothenburg, Sweden.

Internationally, investigators have been working to reduce morbidity for women who donate their uterus. Since the vascular tree of the uterus must also be dissected and preserved during the organ harvesting procedure, operative time is longer than for a simple hysterectomy, and there’s increased risk of urinary dysfunction because of the extensive dissection, Antonio R. Gargiulo, MD, said in an interview.*

Dr. Gargiulo, medical director of the center for robotic surgery at Brigham and Women’s Hospital, Boston, said that the first few uterine harvest procedures took much longer, up to 10 hours. But, he said, the vascular harvest “is well within the capability of the best gynecologic oncology surgeons,” and newer techniques may further reduce the donor morbidity.

Using the utero-ovarian vein as the primary outflow tract is “a promising modification of this operation” that may be the “technical key to making this procedure the least morbid possible,” said Dr. Gargiulo, a reproductive endocrinologist who is involved with the development of a uterine transplantation program at the Brigham and Women’s Hospital.

Dr. Johannesson said that the Baylor team currently dissects the entire uterine vascular tree and reanastomoses what vessels they can. She pointed out that even with the best imaging techniques, it can be difficult to ascertain the best vessels until the surgery’s actually being performed.

All of the surgeons interviewed emphasized that each procedure represents an opportunity for growth in a young field with a steep learning curve. They expect ongoing technical advances, including the use of robotic surgery, to reduce operative time and lessen morbidity.

It’s worth pressing on in this field for the sake of the patients, said Dr. Testa, speaking for his transplant team. “We are all humbled by the depth of the desire of a woman to carry her own pregnancy.”

Dr. Johannesson said that she hopes that today when gynecologists talk to teenage patients who have absolute uterine infertility, they will be offering a message of hope. “When they meet young women, they should tell them that they shouldn’t stop hoping,” she said. “There is hope that they will be able to carry their own pregnancy.”

Dr. Gargiulo has been a paid consultant for Kawasaki Robotics and OmniGuide. Dr. Testa and Dr. Johannesson reported that they had no relevant conflicts of interest.
 

*Correction, 12/12/17: The reason for the increased risk of urinary dysfunction was misstated.

[email protected]
On Twitter @karioakes

A woman with a transplanted uterus gave birth to a live baby boy in Dallas, the first birth from a transplanted uterus in the United States. It is also the first birth resulting from uterine transplantation to be performed outside of Sweden, where a total of eight births have occurred.

“This really confirms that this is doable, that it can be replicated,” said Giuliano Testa, MD, chief of abdominal transplantation at Baylor University Medical Center, Dallas, during a press conference to discuss the birth.

With time, Dr. Testa said in an interview, he foresees uterine transplantation becoming a realistic alternative for some women. “It’s a great solution for the woman who really wants to carry her own pregnancy.”

“This is the best of academic medicine,” Dr. Testa said of the international collaboration and transparency among investigators working in the nascent field. “The communication is constant; we learn from each other ... I am very excited about what will come in the future.”

In order to protect the privacy of the patient and her family, physicians did not disclose the patient’s name, location, or the exact date of the birth. The patient also did not wish to share the infant’s gestational age at birth or birth weight, or whether the uterus had been removed after the birth. Transplanted uteri are meant to be removed after one or two pregnancies, so the recipient doesn’t have to be on lifelong immunosuppression once the desired pregnancies have been achieved.

However, during the press conference, the surgical team shared that the mother is home and doing well, and the infant is on room air and feeding well. A video of the birth shown at the press conference showed a vernix-covered baby who began crying vigorously even before his feet were delivered during the cesarean delivery.

The transplantation, pregnancy via in vitro fertilization, and subsequent birth were accomplished as part of a 10-patient clinical trial of uterine transplantation at Baylor University Medical Center. Women aged 20-35 years with absolute uterine factor infertility, such as those with congenitally absent uteri, were eligible to participate. Donors must have had one full-term delivery and may be aged 30-65 years; menopause does not render a uterus incapable of carrying a pregnancy. Donors are able to retain their ovaries.

Another study participant at Baylor is late into her pregnancy as well, Dr. Testa said.

The extensive screening process for uterus donation ensures that the team is using “a good organ from a good donor,” said Liza Johannesson, MD, PhD. In an interview, she said that the harvest is now about a 4-5 hour open procedure that takes the uterus, the cervix, and the very superior portion of the vagina, as well as the uterine arteries and veins out to the internal iliac bilaterally. The utero-ovarian veins also are harvested.

To date, the six women who have been donors in the Baylor program have not had serious complications and have returned to their previous level of function, said Dr. Johannesson, who came to Baylor from Sahlgrenska University Hospital’s successful uterine transplantation team in Gothenburg, Sweden.

Internationally, investigators have been working to reduce morbidity for women who donate their uterus. Since the vascular tree of the uterus must also be dissected and preserved during the organ harvesting procedure, operative time is longer than for a simple hysterectomy, and there’s increased risk of urinary dysfunction because of the extensive dissection, Antonio R. Gargiulo, MD, said in an interview.*

Dr. Gargiulo, medical director of the center for robotic surgery at Brigham and Women’s Hospital, Boston, said that the first few uterine harvest procedures took much longer, up to 10 hours. But, he said, the vascular harvest “is well within the capability of the best gynecologic oncology surgeons,” and newer techniques may further reduce the donor morbidity.

Using the utero-ovarian vein as the primary outflow tract is “a promising modification of this operation” that may be the “technical key to making this procedure the least morbid possible,” said Dr. Gargiulo, a reproductive endocrinologist who is involved with the development of a uterine transplantation program at the Brigham and Women’s Hospital.

Dr. Johannesson said that the Baylor team currently dissects the entire uterine vascular tree and reanastomoses what vessels they can. She pointed out that even with the best imaging techniques, it can be difficult to ascertain the best vessels until the surgery’s actually being performed.

All of the surgeons interviewed emphasized that each procedure represents an opportunity for growth in a young field with a steep learning curve. They expect ongoing technical advances, including the use of robotic surgery, to reduce operative time and lessen morbidity.

It’s worth pressing on in this field for the sake of the patients, said Dr. Testa, speaking for his transplant team. “We are all humbled by the depth of the desire of a woman to carry her own pregnancy.”

Dr. Johannesson said that she hopes that today when gynecologists talk to teenage patients who have absolute uterine infertility, they will be offering a message of hope. “When they meet young women, they should tell them that they shouldn’t stop hoping,” she said. “There is hope that they will be able to carry their own pregnancy.”

Dr. Gargiulo has been a paid consultant for Kawasaki Robotics and OmniGuide. Dr. Testa and Dr. Johannesson reported that they had no relevant conflicts of interest.
 

*Correction, 12/12/17: The reason for the increased risk of urinary dysfunction was misstated.

[email protected]
On Twitter @karioakes

Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.