The research paradigm had been: examine a person’s traits or symptomsthen, then search for genes or gene variants that cause or contribute to them. But it was difficult for researchers to recontact people with genotypes of interest for “downstream” follow-up.

Now, the National Institute of Health (NIH) and Inova Health System are launching The Genomic Ascertainment Cohort (TGAC), a 2-year pilot project that will allow researchers to recall genotyped people and examine the influence of genes and gene variants on phenotypes. “This is essentially match-making between genes and gene variants and the researchers who study them,” says Richard Siegel, MD, PhD, TGAC co-organizer, and clinical director and chief of the Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. For instance, a researcher might locate a genotype of interest in the database and ask participants with the genotype to come to the NIH Clinical Center in Bethesda.

Participating NIH institutes will contribute genome and exome sequences from existing research programs to the database. Another 1,000 patients will be recruited to have genome sequencing performed. Half of the new recruits will be from Hispanic backgrounds.

The researchers are aiming for 10,000 genomes and exomes to allow recruitment of people with both common and rarer gene variants.

“We’re trying to advance science in a new, creative, and slightly radical way,” says Leslie Biesecker, MD, TGAC co-organizer and chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. “We’re especially interested in using this as a platform to test our ability to predict phenotype from genotype—one of the key underpinnings of predictive genomic medicine.”

The research paradigm had been: examine a person’s traits or symptomsthen, then search for genes or gene variants that cause or contribute to them. But it was difficult for researchers to recontact people with genotypes of interest for “downstream” follow-up.

Now, the National Institute of Health (NIH) and Inova Health System are launching The Genomic Ascertainment Cohort (TGAC), a 2-year pilot project that will allow researchers to recall genotyped people and examine the influence of genes and gene variants on phenotypes. “This is essentially match-making between genes and gene variants and the researchers who study them,” says Richard Siegel, MD, PhD, TGAC co-organizer, and clinical director and chief of the Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. For instance, a researcher might locate a genotype of interest in the database and ask participants with the genotype to come to the NIH Clinical Center in Bethesda.

Participating NIH institutes will contribute genome and exome sequences from existing research programs to the database. Another 1,000 patients will be recruited to have genome sequencing performed. Half of the new recruits will be from Hispanic backgrounds.

The researchers are aiming for 10,000 genomes and exomes to allow recruitment of people with both common and rarer gene variants.

“We’re trying to advance science in a new, creative, and slightly radical way,” says Leslie Biesecker, MD, TGAC co-organizer and chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. “We’re especially interested in using this as a platform to test our ability to predict phenotype from genotype—one of the key underpinnings of predictive genomic medicine.”

The research paradigm had been: examine a person’s traits or symptomsthen, then search for genes or gene variants that cause or contribute to them. But it was difficult for researchers to recontact people with genotypes of interest for “downstream” follow-up.

Now, the National Institute of Health (NIH) and Inova Health System are launching The Genomic Ascertainment Cohort (TGAC), a 2-year pilot project that will allow researchers to recall genotyped people and examine the influence of genes and gene variants on phenotypes. “This is essentially match-making between genes and gene variants and the researchers who study them,” says Richard Siegel, MD, PhD, TGAC co-organizer, and clinical director and chief of the Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. For instance, a researcher might locate a genotype of interest in the database and ask participants with the genotype to come to the NIH Clinical Center in Bethesda.

Participating NIH institutes will contribute genome and exome sequences from existing research programs to the database. Another 1,000 patients will be recruited to have genome sequencing performed. Half of the new recruits will be from Hispanic backgrounds.

The researchers are aiming for 10,000 genomes and exomes to allow recruitment of people with both common and rarer gene variants.

“We’re trying to advance science in a new, creative, and slightly radical way,” says Leslie Biesecker, MD, TGAC co-organizer and chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. “We’re especially interested in using this as a platform to test our ability to predict phenotype from genotype—one of the key underpinnings of predictive genomic medicine.”

Photo by Barry Riley

Exposure to the 9/11 World Trade Center (WTC) disaster site may increase the risk of monoclonal gammopathy of undetermined significance (MGUS) and early development of multiple myeloma (MM).

Researchers found that firefighters exposed to the site had a nearly 2-fold higher risk of MGUS than a control population.

And those firefighters who developed MM were diagnosed 12 years earlier than MM patients in the general US population.

These findings were published in JAMA Oncology.

Previous studies suggested that MGUS and MM tend to develop after exposure to toxic chemicals, and individuals exposed to the WTC disaster site have an increased risk of developing cancers.

The aerosolized dust from the collapsed WTC towers exposed firefighters and other first responders to high levels of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins, asbestos, and other potential carcinogens, as well as diesel smoke from heavy machinery used in the 10-month rescue and recovery effort.

“With our 2011 study in The Lancet, we were the first to show that first responders were more likely to get many different types of cancer,” said David J. Prezant, MD, of Albert Einstein College of Medicine in Bronx, New York.

“We carried out this new study to do more than just treat cancer. We wanted to find early, predictive signs of cancer that would allow us to screen people and monitor those found to be at risk. By detecting MGUS, which predicts the development of multiple myeloma, we are able to do that.”

For statistical reasons, the study population was limited to 781 white, male WTC-exposed firefighters ages 50 to 79.

The researchers assess the prevalence of MGUS in these firefighters and compared it to the prevalence of MGUS in a non-exposed comparison group—men living in Olmsted County, Minnesota.

The prevalence of MGUS was 1.8-fold higher in the firefighters. There were 7.63 cases of MGUS per 100 firefighters and 4.34 cases per 100 non-exposed men.

The researchers also found the prevalence of light-chain MGUS was 3.1-fold higher in the firefighters than in the controls. The prevalence rate of light-chain MGUS was 3.08 and 0.98 per 100 persons, respectively.

“We saw a significantly higher incidence of MGUS in these first responders, and they’re developing it at a young age,” said study author Amit Verma, MBBS, of Albert Einstein College of Medicine.

The subjects’ early development of MGUS suggests they may face an increased risk for early onset MM as well.

In a separate analysis, the researchers examined 16 cases of MM among white, male WTC-exposed firefighters diagnosed between September 12, 2001, and July 1, 2017.

Their average age at diagnosis was 57, or 12 years younger than the average age for MM diagnosis in the US.

The researchers also found that 7 of 14 evaluable cases were light-chain MM. They said this is more than double the rate observed in other populations—50% vs 20%.

In the population of firefighters screened for MGUS, 38% (18/47) of those who had MGUS were found to have the light-chain subtype.

The researchers said these findings are of interest because previous research revealed associations between light-chain MM/MGUS and exposure to toxins and chronic immune stimulation.

The team also assessed CD20 expression in a subset of 7 MM patients. Five of these patients (71%) had CD20-positive cells, which is associated with poor prognosis.

Based on these findings, the researchers recommend that physicians screen first responders exposed to the WTC disaster site for MGUS.

“Screening for multiple myeloma risk by testing for MGUS is something we can offer these first responders, which is why this study is important,” Dr Prezant said.

Photo by Barry Riley

Exposure to the 9/11 World Trade Center (WTC) disaster site may increase the risk of monoclonal gammopathy of undetermined significance (MGUS) and early development of multiple myeloma (MM).

Researchers found that firefighters exposed to the site had a nearly 2-fold higher risk of MGUS than a control population.

And those firefighters who developed MM were diagnosed 12 years earlier than MM patients in the general US population.

These findings were published in JAMA Oncology.

Previous studies suggested that MGUS and MM tend to develop after exposure to toxic chemicals, and individuals exposed to the WTC disaster site have an increased risk of developing cancers.

The aerosolized dust from the collapsed WTC towers exposed firefighters and other first responders to high levels of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins, asbestos, and other potential carcinogens, as well as diesel smoke from heavy machinery used in the 10-month rescue and recovery effort.

“With our 2011 study in The Lancet, we were the first to show that first responders were more likely to get many different types of cancer,” said David J. Prezant, MD, of Albert Einstein College of Medicine in Bronx, New York.

“We carried out this new study to do more than just treat cancer. We wanted to find early, predictive signs of cancer that would allow us to screen people and monitor those found to be at risk. By detecting MGUS, which predicts the development of multiple myeloma, we are able to do that.”

For statistical reasons, the study population was limited to 781 white, male WTC-exposed firefighters ages 50 to 79.

The researchers assess the prevalence of MGUS in these firefighters and compared it to the prevalence of MGUS in a non-exposed comparison group—men living in Olmsted County, Minnesota.

The prevalence of MGUS was 1.8-fold higher in the firefighters. There were 7.63 cases of MGUS per 100 firefighters and 4.34 cases per 100 non-exposed men.

The researchers also found the prevalence of light-chain MGUS was 3.1-fold higher in the firefighters than in the controls. The prevalence rate of light-chain MGUS was 3.08 and 0.98 per 100 persons, respectively.

“We saw a significantly higher incidence of MGUS in these first responders, and they’re developing it at a young age,” said study author Amit Verma, MBBS, of Albert Einstein College of Medicine.

The subjects’ early development of MGUS suggests they may face an increased risk for early onset MM as well.

In a separate analysis, the researchers examined 16 cases of MM among white, male WTC-exposed firefighters diagnosed between September 12, 2001, and July 1, 2017.

Their average age at diagnosis was 57, or 12 years younger than the average age for MM diagnosis in the US.

The researchers also found that 7 of 14 evaluable cases were light-chain MM. They said this is more than double the rate observed in other populations—50% vs 20%.

In the population of firefighters screened for MGUS, 38% (18/47) of those who had MGUS were found to have the light-chain subtype.

The researchers said these findings are of interest because previous research revealed associations between light-chain MM/MGUS and exposure to toxins and chronic immune stimulation.

The team also assessed CD20 expression in a subset of 7 MM patients. Five of these patients (71%) had CD20-positive cells, which is associated with poor prognosis.

Based on these findings, the researchers recommend that physicians screen first responders exposed to the WTC disaster site for MGUS.

“Screening for multiple myeloma risk by testing for MGUS is something we can offer these first responders, which is why this study is important,” Dr Prezant said.

Photo by Barry Riley

Exposure to the 9/11 World Trade Center (WTC) disaster site may increase the risk of monoclonal gammopathy of undetermined significance (MGUS) and early development of multiple myeloma (MM).

Researchers found that firefighters exposed to the site had a nearly 2-fold higher risk of MGUS than a control population.

And those firefighters who developed MM were diagnosed 12 years earlier than MM patients in the general US population.

These findings were published in JAMA Oncology.

Previous studies suggested that MGUS and MM tend to develop after exposure to toxic chemicals, and individuals exposed to the WTC disaster site have an increased risk of developing cancers.

The aerosolized dust from the collapsed WTC towers exposed firefighters and other first responders to high levels of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins, asbestos, and other potential carcinogens, as well as diesel smoke from heavy machinery used in the 10-month rescue and recovery effort.

“With our 2011 study in The Lancet, we were the first to show that first responders were more likely to get many different types of cancer,” said David J. Prezant, MD, of Albert Einstein College of Medicine in Bronx, New York.

“We carried out this new study to do more than just treat cancer. We wanted to find early, predictive signs of cancer that would allow us to screen people and monitor those found to be at risk. By detecting MGUS, which predicts the development of multiple myeloma, we are able to do that.”

For statistical reasons, the study population was limited to 781 white, male WTC-exposed firefighters ages 50 to 79.

The researchers assess the prevalence of MGUS in these firefighters and compared it to the prevalence of MGUS in a non-exposed comparison group—men living in Olmsted County, Minnesota.

The prevalence of MGUS was 1.8-fold higher in the firefighters. There were 7.63 cases of MGUS per 100 firefighters and 4.34 cases per 100 non-exposed men.

The researchers also found the prevalence of light-chain MGUS was 3.1-fold higher in the firefighters than in the controls. The prevalence rate of light-chain MGUS was 3.08 and 0.98 per 100 persons, respectively.

“We saw a significantly higher incidence of MGUS in these first responders, and they’re developing it at a young age,” said study author Amit Verma, MBBS, of Albert Einstein College of Medicine.

The subjects’ early development of MGUS suggests they may face an increased risk for early onset MM as well.

In a separate analysis, the researchers examined 16 cases of MM among white, male WTC-exposed firefighters diagnosed between September 12, 2001, and July 1, 2017.

Their average age at diagnosis was 57, or 12 years younger than the average age for MM diagnosis in the US.

The researchers also found that 7 of 14 evaluable cases were light-chain MM. They said this is more than double the rate observed in other populations—50% vs 20%.

In the population of firefighters screened for MGUS, 38% (18/47) of those who had MGUS were found to have the light-chain subtype.

The researchers said these findings are of interest because previous research revealed associations between light-chain MM/MGUS and exposure to toxins and chronic immune stimulation.

The team also assessed CD20 expression in a subset of 7 MM patients. Five of these patients (71%) had CD20-positive cells, which is associated with poor prognosis.

Based on these findings, the researchers recommend that physicians screen first responders exposed to the WTC disaster site for MGUS.

“Screening for multiple myeloma risk by testing for MGUS is something we can offer these first responders, which is why this study is important,” Dr Prezant said.

Mantle cell lymphoma

CHICAGO—The radioimmunoconjugate ¹⁷⁷Lu-NNV003 has demonstrated activity against non-Hodgkin lymphomas (NHLs).

Experiments showed that ¹⁷⁷Lu-NNV003 can inhibit proliferation in mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL) cell lines.

¹⁷⁷Lu-NNV003 also exhibited an antitumor effect and prolonged survival in mouse models of MCL, DLBCL, and CLL.

These results were presented at the AACR Annual Meeting 2018 (abstract 848).

This research was conducted by employees of Nordic Nanovector and other researchers. Nordic Nanovector is the company developing ¹⁷⁷Lu-NNV003.

¹⁷⁷Lu-NNV003 consists of a chimeric antibody targeting CD37 (NNV003) conjugated with p-SCN-Bn-DOTA, which chelates the β-emitting radionuclide lutetium-177.

The researchers found that ¹⁷⁷Lu-NNV003 inhibited proliferation in all 3 NHL cell lines tested—MEC-2 (CLL), DOHH2 (DLBCL), and REC-1 (MCL). DOHH2 was the most radiosensitive cell line.

The unlabeled NNV003 antibody, on the other hand, did not exhibit an antiproliferative effect in these cell lines. However, NNV003 did induce antibody-dependent cellular cytotoxicity in MEC-2 and DOHH2 cells and antibody-dependent cellular phagocytosis in MEC-2 cells.

The researchers found that ¹⁷⁷Lu-NNV003 targeted CD37-positive cells and demonstrated antitumor effects in mouse models of MCL, CLL, and DLBCL.

REC-1 model

¹⁷⁷Lu-NNV003 prolonged survival in CB17 SCID mice injected with REC-1 cells and cured 50% to 60% of the mice.

Median survival times were 55 days in mice that received sodium chloride (NaCl), 85 days in mice that received NNV003 (0.167 mg/kg), and 61 days in mice that received ¹⁷⁷Lu-IgG1 (100 MBq/kg).

On the other hand, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 152 days (100 MBq/kg), or the median survival was not reached (50 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of NaCl (P<0.001) or ¹⁷⁷Lu-IgG1 (P<0.002).

MEC-2 model

¹⁷⁷Lu-NNV003 also prolonged survival in NRG mice injected with MEC-2 cells.

The median survival was 21 days in mice that received NaCl, NNV003 (2 x 0.33 mg/kg), or ¹⁷⁷Lu-IgG1 (200 MBq/kg).

However, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 32 days (200 MBq/kg) or 29 days (2 x 200 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of ¹⁷⁷Lu-IgG1 (P<0.025) or 2 x NNV003 (P<0.02).

DOHH2 model

RAG-2 mice injected with DOHH2 cells had survival times surpassing 200 days after treatment with NNV003 or ¹⁷⁷Lu-NNV003.

The median survival was not reached in mice that received NNV003 (at 2 or 30 mg/kg) or ¹⁷⁷Lu-NNV003 (at 200, 300, or 400 MBq/kg). But the median survival was 46 days in mice that received NaCl and 47 days in mice that received ¹⁷⁷Lu-IgG1 (300 MBq/kg).

The difference in survival was significant for recipients of NNV003 or ¹⁷⁷Lu-NNV003 compared to recipients of ¹⁷⁷Lu-IgG1 or NaCl (P<0.001 for all).

Toxicity and biodistribution

The researchers noted that the ¹⁷⁷Lu-labeled antibodies caused transient hematologic toxicity in the mice.

In the MEC-2 and DOHH2 models, there was no redistribution of ¹⁷⁷Lu-NNV003 in organs after initial uptake. (The researchers did not report on biodistribution in the REC-1 model.)

¹⁷⁷Lu-NNV003 had low uptake in the liver, spleen, kidneys, and femur. The researchers said this suggests ¹⁷⁷Lu-NNV003 is stable in vivo, as free lutetium-177 tends to accumulate in bones.

Mantle cell lymphoma

CHICAGO—The radioimmunoconjugate ¹⁷⁷Lu-NNV003 has demonstrated activity against non-Hodgkin lymphomas (NHLs).

Experiments showed that ¹⁷⁷Lu-NNV003 can inhibit proliferation in mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL) cell lines.

¹⁷⁷Lu-NNV003 also exhibited an antitumor effect and prolonged survival in mouse models of MCL, DLBCL, and CLL.

These results were presented at the AACR Annual Meeting 2018 (abstract 848).

This research was conducted by employees of Nordic Nanovector and other researchers. Nordic Nanovector is the company developing ¹⁷⁷Lu-NNV003.

¹⁷⁷Lu-NNV003 consists of a chimeric antibody targeting CD37 (NNV003) conjugated with p-SCN-Bn-DOTA, which chelates the β-emitting radionuclide lutetium-177.

The researchers found that ¹⁷⁷Lu-NNV003 inhibited proliferation in all 3 NHL cell lines tested—MEC-2 (CLL), DOHH2 (DLBCL), and REC-1 (MCL). DOHH2 was the most radiosensitive cell line.

The unlabeled NNV003 antibody, on the other hand, did not exhibit an antiproliferative effect in these cell lines. However, NNV003 did induce antibody-dependent cellular cytotoxicity in MEC-2 and DOHH2 cells and antibody-dependent cellular phagocytosis in MEC-2 cells.

The researchers found that ¹⁷⁷Lu-NNV003 targeted CD37-positive cells and demonstrated antitumor effects in mouse models of MCL, CLL, and DLBCL.

REC-1 model

¹⁷⁷Lu-NNV003 prolonged survival in CB17 SCID mice injected with REC-1 cells and cured 50% to 60% of the mice.

Median survival times were 55 days in mice that received sodium chloride (NaCl), 85 days in mice that received NNV003 (0.167 mg/kg), and 61 days in mice that received ¹⁷⁷Lu-IgG1 (100 MBq/kg).

On the other hand, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 152 days (100 MBq/kg), or the median survival was not reached (50 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of NaCl (P<0.001) or ¹⁷⁷Lu-IgG1 (P<0.002).

MEC-2 model

¹⁷⁷Lu-NNV003 also prolonged survival in NRG mice injected with MEC-2 cells.

The median survival was 21 days in mice that received NaCl, NNV003 (2 x 0.33 mg/kg), or ¹⁷⁷Lu-IgG1 (200 MBq/kg).

However, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 32 days (200 MBq/kg) or 29 days (2 x 200 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of ¹⁷⁷Lu-IgG1 (P<0.025) or 2 x NNV003 (P<0.02).

DOHH2 model

RAG-2 mice injected with DOHH2 cells had survival times surpassing 200 days after treatment with NNV003 or ¹⁷⁷Lu-NNV003.

The median survival was not reached in mice that received NNV003 (at 2 or 30 mg/kg) or ¹⁷⁷Lu-NNV003 (at 200, 300, or 400 MBq/kg). But the median survival was 46 days in mice that received NaCl and 47 days in mice that received ¹⁷⁷Lu-IgG1 (300 MBq/kg).

The difference in survival was significant for recipients of NNV003 or ¹⁷⁷Lu-NNV003 compared to recipients of ¹⁷⁷Lu-IgG1 or NaCl (P<0.001 for all).

Toxicity and biodistribution

The researchers noted that the ¹⁷⁷Lu-labeled antibodies caused transient hematologic toxicity in the mice.

In the MEC-2 and DOHH2 models, there was no redistribution of ¹⁷⁷Lu-NNV003 in organs after initial uptake. (The researchers did not report on biodistribution in the REC-1 model.)

¹⁷⁷Lu-NNV003 had low uptake in the liver, spleen, kidneys, and femur. The researchers said this suggests ¹⁷⁷Lu-NNV003 is stable in vivo, as free lutetium-177 tends to accumulate in bones.

Mantle cell lymphoma

CHICAGO—The radioimmunoconjugate ¹⁷⁷Lu-NNV003 has demonstrated activity against non-Hodgkin lymphomas (NHLs).

Experiments showed that ¹⁷⁷Lu-NNV003 can inhibit proliferation in mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL) cell lines.

¹⁷⁷Lu-NNV003 also exhibited an antitumor effect and prolonged survival in mouse models of MCL, DLBCL, and CLL.

These results were presented at the AACR Annual Meeting 2018 (abstract 848).

This research was conducted by employees of Nordic Nanovector and other researchers. Nordic Nanovector is the company developing ¹⁷⁷Lu-NNV003.

¹⁷⁷Lu-NNV003 consists of a chimeric antibody targeting CD37 (NNV003) conjugated with p-SCN-Bn-DOTA, which chelates the β-emitting radionuclide lutetium-177.

The researchers found that ¹⁷⁷Lu-NNV003 inhibited proliferation in all 3 NHL cell lines tested—MEC-2 (CLL), DOHH2 (DLBCL), and REC-1 (MCL). DOHH2 was the most radiosensitive cell line.

The unlabeled NNV003 antibody, on the other hand, did not exhibit an antiproliferative effect in these cell lines. However, NNV003 did induce antibody-dependent cellular cytotoxicity in MEC-2 and DOHH2 cells and antibody-dependent cellular phagocytosis in MEC-2 cells.

The researchers found that ¹⁷⁷Lu-NNV003 targeted CD37-positive cells and demonstrated antitumor effects in mouse models of MCL, CLL, and DLBCL.

REC-1 model

¹⁷⁷Lu-NNV003 prolonged survival in CB17 SCID mice injected with REC-1 cells and cured 50% to 60% of the mice.

Median survival times were 55 days in mice that received sodium chloride (NaCl), 85 days in mice that received NNV003 (0.167 mg/kg), and 61 days in mice that received ¹⁷⁷Lu-IgG1 (100 MBq/kg).

On the other hand, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 152 days (100 MBq/kg), or the median survival was not reached (50 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of NaCl (P<0.001) or ¹⁷⁷Lu-IgG1 (P<0.002).

MEC-2 model

¹⁷⁷Lu-NNV003 also prolonged survival in NRG mice injected with MEC-2 cells.

The median survival was 21 days in mice that received NaCl, NNV003 (2 x 0.33 mg/kg), or ¹⁷⁷Lu-IgG1 (200 MBq/kg).

However, mice treated with ¹⁷⁷Lu-NNV003 had a median survival of 32 days (200 MBq/kg) or 29 days (2 x 200 MBq/kg).

The difference in survival was significant for ¹⁷⁷Lu-NNV003 recipients compared to recipients of ¹⁷⁷Lu-IgG1 (P<0.025) or 2 x NNV003 (P<0.02).

DOHH2 model

RAG-2 mice injected with DOHH2 cells had survival times surpassing 200 days after treatment with NNV003 or ¹⁷⁷Lu-NNV003.

The median survival was not reached in mice that received NNV003 (at 2 or 30 mg/kg) or ¹⁷⁷Lu-NNV003 (at 200, 300, or 400 MBq/kg). But the median survival was 46 days in mice that received NaCl and 47 days in mice that received ¹⁷⁷Lu-IgG1 (300 MBq/kg).

The difference in survival was significant for recipients of NNV003 or ¹⁷⁷Lu-NNV003 compared to recipients of ¹⁷⁷Lu-IgG1 or NaCl (P<0.001 for all).

Toxicity and biodistribution

The researchers noted that the ¹⁷⁷Lu-labeled antibodies caused transient hematologic toxicity in the mice.

In the MEC-2 and DOHH2 models, there was no redistribution of ¹⁷⁷Lu-NNV003 in organs after initial uptake. (The researchers did not report on biodistribution in the REC-1 model.)

¹⁷⁷Lu-NNV003 had low uptake in the liver, spleen, kidneys, and femur. The researchers said this suggests ¹⁷⁷Lu-NNV003 is stable in vivo, as free lutetium-177 tends to accumulate in bones.

Woman stressed at work

A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.

In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.

More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.

“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.

“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”

Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.

The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).

The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).

The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.

Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.

Results

Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).

Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.

The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).

In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.

The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.

However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.

“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.

“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”

Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”

Woman stressed at work

A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.

In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.

More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.

“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.

“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”

Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.

The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).

The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).

The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.

Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.

Results

Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).

Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.

The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).

In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.

The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.

However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.

“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.

“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”

Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”

Woman stressed at work

A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.

In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.

More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.

“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.

“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”

Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.

The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).

The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).

The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.

Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.

Results

Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).

Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.

The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).

In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.

The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.

However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.

“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.

“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”

Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”

Hay, A.D., et al, JAMA 318(8):721, August 22, 2017

BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.

METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).

RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).

CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references (alastair.hay@bristol.ac.uk – no reprints)

Hay, A.D., et al, JAMA 318(8):721, August 22, 2017

BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.

METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).

RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).

CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references (alastair.hay@bristol.ac.uk – no reprints)

Hay, A.D., et al, JAMA 318(8):721, August 22, 2017

BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.

METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).

RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).

CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references (alastair.hay@bristol.ac.uk – no reprints)

WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.

“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”

The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.

Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.

“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented. “We need EMS for the brain; we need one number to call.”

Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.

Dr. Hogan had no disclosures.

mzoler@mdedge.com

WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.

“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”

The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.

Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.

“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented. “We need EMS for the brain; we need one number to call.”

Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.

Dr. Hogan had no disclosures.

mzoler@mdedge.com

WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.

“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”

The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.

Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.

“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented. “We need EMS for the brain; we need one number to call.”

Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.

Dr. Hogan had no disclosures.

mzoler@mdedge.com

The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.

This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.

Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.

The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.

The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.

HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.

Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.

The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

ilacy@mdedge.com

The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.

This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.

Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.

The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.

The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.

HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.

Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.

The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

ilacy@mdedge.com

The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.

This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.

Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.

The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.

The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.

HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.

Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.

The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

ilacy@mdedge.com

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

koakes@mdedge.com

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

koakes@mdedge.com

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

koakes@mdedge.com

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, in recent years, novel therapeutic approaches have been developed to focus on the older AML population. Have we begun to witness an improvement in the survival of these patients?

Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.

References

1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.

2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.

3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.

4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.

5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.

6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.

7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.

8. Lancet JE et al. Blood 2016 128:906.

9. Cortes JE et al. Blood 2016 128:99.

10. DiNardo CD et al. Blood 2017 130:2628.

11. Wei A et al. Blood 2017 130:890.

12. Extermann M et al. SIOG 2017.

The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, in recent years, novel therapeutic approaches have been developed to focus on the older AML population. Have we begun to witness an improvement in the survival of these patients?

Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.

References

1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.

2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.

3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.

4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.

5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.

6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.

7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.

8. Lancet JE et al. Blood 2016 128:906.

9. Cortes JE et al. Blood 2016 128:99.

10. DiNardo CD et al. Blood 2017 130:2628.

11. Wei A et al. Blood 2017 130:890.

12. Extermann M et al. SIOG 2017.

The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, in recent years, novel therapeutic approaches have been developed to focus on the older AML population. Have we begun to witness an improvement in the survival of these patients?

Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.

References

1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.

2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.

3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.

4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.

5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.

6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.

7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.

8. Lancet JE et al. Blood 2016 128:906.

9. Cortes JE et al. Blood 2016 128:99.

10. DiNardo CD et al. Blood 2017 130:2628.

11. Wei A et al. Blood 2017 130:890.

12. Extermann M et al. SIOG 2017.

Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.

• DCI is a common complication of subarachnoid hemorrhage.
• Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
• Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
• Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.

Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232

Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.

• DCI is a common complication of subarachnoid hemorrhage.
• Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
• Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
• Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.

Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232

Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.

• DCI is a common complication of subarachnoid hemorrhage.
• Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
• Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
• Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.

Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232