Cord blood donation

Photo courtesy of NHS

Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.

However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.

The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.

By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.

“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.

Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.

Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.

Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.

The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.

The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.

The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.

In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant.

Cord blood donation

Photo courtesy of NHS

Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.

However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.

The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.

By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.

“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.

Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.

Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.

Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.

The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.

The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.

The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.

In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant.

Cord blood donation

Photo courtesy of NHS

Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.

However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.

The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.

By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.

“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.

Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.

Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.

Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.

The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.

The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.

The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.

In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant.

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.

And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.

Results of the survey were published in JAMA Oncology.

“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.

“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”

Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.

The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”

Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.

Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.

“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”

The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.

The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.

For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.

“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.

And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.

Results of the survey were published in JAMA Oncology.

“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.

“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”

Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.

The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”

Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.

Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.

“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”

The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.

The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.

For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.

“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

In a survey of advanced cancer patients and their oncologists, differing opinions about prognosis were common.

And the vast majority of patients didn’t know their doctors held different opinions about how long the patients might live.

Results of the survey were published in JAMA Oncology.

“We’ve discovered 2 important things happening between oncologists and patients with advanced cancer,” said study author Ronald M. Epstein, MD, of the University of Rochester Medical Center in Rochester, New York.

“First, some patients might know the doctor’s prognosis estimate, but the patient chooses to disagree, often because they believe other sources. And, second, some patients think that their doctor agrees with their opinion about prognosis but, in fact, the doctor doesn’t.”

Dr Epstein and his colleagues surveyed 236 patients with stage 3 or 4 cancer. According to medical evidence, fewer than 5% of these patients would be expected to live for 5 years.

The 38 oncologists who treated these patients were also surveyed. The doctors were asked,“What do you believe are the chances that this patient will live for 2 years or more?” And the patients were asked, “What do you believe are the chances that you will live for 2 years or more?”

Additional survey questions gauged whether patients knew their prognosis opinions differed from their doctors and to what extent treatment options were discussed in the context of life expectancy.

Among the 236 patients, 68% rated their survival prognosis differently than their oncologists, and 89% of these patients did not realize their opinions differed from their oncologists. In nearly all cases (96%), the patients were more optimistic than their doctors.

“Of course, it’s only possible for doctors to provide a ball-park estimate about life expectancy, and some people do beat the odds,” Dr Epstein noted. “But when a patient with very advanced cancer says that he has a 90% to 100% chance of being alive in 2 years and his oncologist believes that chance is more like 10%, there’s a problem.”

The challenge, according to Dr Epstein and his colleagues, is that talking about a cancer prognosis is not a straightforward exchange of information. It occurs in the context of fear, confusion, and uncertainty.

The researchers said prognosis should be addressed in several conversations about personal values and treatment goals. When doctor-patient communication is poor, it can result in mutual regret about end-of-life circumstances.

For example, nearly all of the patients surveyed said they wanted to be involved in treatment decisions. And 70% said they preferred supportive care at the end of their lives as opposed to aggressive therapy. However, as the researchers pointed out, making an informed decision requires knowing when death is approaching.

“When people think they’ll live a very long time with cancer, despite evidence to the contrary, they may end up taking more aggressive chemotherapy and agreeing to be placed on ventilators or dialysis, paradoxically reducing their quality of life, keeping them from enjoying time with family, and sometimes even shortening their lives,” Dr Epstein said. “So it’s very important for doctors and patients to be on the same page.”

Woman on a scale

A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.

Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.

Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.

“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”

Dr Duggan and her colleagues described this investigation in Cancer Research.

The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.

The women were randomized to 1 of 4 study arms:

• A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
• An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
• A combined diet and exercise arm
• A control arm.

The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.

They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.

The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).

Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.

Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).

Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).

And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).

The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.

“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”

“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”

Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.

Woman on a scale

A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.

Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.

Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.

“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”

Dr Duggan and her colleagues described this investigation in Cancer Research.

The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.

The women were randomized to 1 of 4 study arms:

• A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
• An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
• A combined diet and exercise arm
• A control arm.

The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.

They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.

The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).

Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.

Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).

Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).

And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).

The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.

“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”

“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”

Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.

Woman on a scale

A study of more than 400 women suggests that losing weight can reduce levels of cancer-promoting proteins in the blood.

Overweight or obese women who lost weight over a 12-month period—through diet alone or both diet and exercise—significantly lowered their levels of proteins that play a role in angiogenesis.

Researchers say this finding suggests that losing weight might help reduce the risk of developing certain cancers.

“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” said Catherine Duggan, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“However, we don’t know exactly why. We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”

Dr Duggan and her colleagues described this investigation in Cancer Research.

The team studied 439 women who were postmenopausal and overweight or obese but were otherwise healthy and ranged in age from 50 to 75.

The women were randomized to 1 of 4 study arms:

• A diet arm, in which women restricted their calorie intake to no more than 2000 kcal per day that included less than 30% of fat calories
• An aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days a week
• A combined diet and exercise arm
• A control arm.

The researchers collected blood samples at baseline and at 12 months, measuring levels of the angiogenesis-related proteins VEGF, PAI-1, and PEDF.

They also measured weight loss at 12 months and found that women in all 3 intervention arms had a significantly higher mean weight loss than women in the control arm.

The mean weight loss was 0.8% of body weight for women in the control arm, 2.4% for women in the exercise arm (P=0.03), 8.5% for women in the diet arm (P<0.001), and 10.8% for women in the diet and exercise arm (P<0.001).

Compared with women in the control arm, those in the diet-only arm and the diet and exercise arm had significantly lower levels of the angiogenesis-related proteins at 12 months. However, such effects were not apparent among women in the exercise-only arm.

Specifically, women in the diet and exercise arm had a significantly greater reduction in PAI-1 at 12 months than women in the control arm (-19.3% and +3.48%, respectively, P<0.0001).

Women in the diet-only arm and the diet and exercise arm had significantly greater reductions in PEDF than controls (-9.20%, -9.90%, and +0.18%, respectively, both P<0.0001).

And women in the diet-only arm (-8.25%, P=0.0005) and the diet and exercise arm (-9.98%, P<0.0001) had significantly greater reductions in VEGF than controls (-1.21%).

The researchers also observed a linear trend in the reductions. So the more weight loss the women experienced, the greater the reduction in angiogenesis-related protein levels.

“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Dr Duggan said. “We were surprised by the magnitude of change in these biomarkers with weight loss.”

“While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”

Dr Duggan and her colleagues said limitations of this study include the fact that the researchers only measured 3 angiogenic factors and did not measure them in adipose or other tissues.

Researcher at a computer

Photo by Darren Baker

An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.

For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.

DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.

Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.

“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.

She and her colleagues described this effort in PLOS Computational Biology.

For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.

The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.

The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.

Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.

Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.

The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.

Researcher at a computer

Photo by Darren Baker

An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.

For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.

DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.

Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.

“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.

She and her colleagues described this effort in PLOS Computational Biology.

For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.

The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.

The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.

Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.

Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.

The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.

Researcher at a computer

Photo by Darren Baker

An international competition has produced models that can help predict outcomes in patients with acute myeloid leukemia (AML), according to researchers.

For the competition, known as the DREAM 9 challenge, 31 teams of computational researchers attempted to predict outcomes using data from hundreds of patients with AML.

DREAM, which stands for Dialogue for Reverse Engineering Assessment and Methods, is a platform for crowd-sourced studies that focus on developing computational tools to solve biomedical problems.

Essentially, it’s a competition that serves as a large, long-standing, international scientific collaboration.

“We used DREAM as a way to get general insight into making more accurate predictive models of clinical outcomes,” said Amina Qutub, PhD, of Rice University in Houston, Texas.

She and her colleagues described this effort in PLOS Computational Biology.

For the DREAM 9 challenge, each team was presented with training data from 191 AML patients, which included demographic information, such as age and gender, and more complex proteomic and phosphoprotein data that describes signaling protein pathways believed to play a role in AML.

The teams were also presented with a test set of 100 AML patients and were asked to predict response to therapy, remission duration, or overall survival for these patients.

The top-performing models—by Team EvoMed of Arizona State University and Team Chipmunks of the Ontario Institute for Cancer Research—were able to predict patient response to therapy with an accuracy of close to 80%.

Both of these models were impacted by the perturbation of PIK3CA and NPM1, which singles out these proteins as candidates for further study, according to researchers.

Another discovery resulting from this competition was that, overall, the 31 models were not as effective for predicting outcomes in patients classified as “resistant to therapy” than for responsive patients.

The median model prediction accuracy was 42% for resistant patients and 73% for responsive patients.

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

[email protected]

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

[email protected]

The 9-valent human papillomavirus vaccine was well tolerated in 16-26 year olds and had a safety profile comparable to that of the quadrivalent vaccine, according to an analysis of seven phase III trials.

“The demonstrated efficacy and favorable safety profile of the 9vHPV vaccine support widespread vaccination programs,” reported Dr. Edson D. Moreira Jr. and his associates in Pediatrics.

Vaccines were given in a three-dose regimen: 15,776 male and female patients received at least one dose of the 9-valent vaccine and 7,391 control subjects received at least one dose of the quadrivalent vaccine.

Frequencies of vaccine-related systemic adverse events such as headache and pyrexia were “generally similar” between the two vaccine groups, the investigators reported.

Compared with the quadrivalent vaccine, the 9-valent vaccine was associated with significantly more frequent adverse events at the injection site, including pain (84% vs. 90%), swelling (29% vs. 40%), and erythema (34% vs. 26%). Most of these reactions in both groups were mild to moderate in intensity, however.

Discontinuations and vaccine-related serious adverse events in the 9-valent vaccine group were rare (0.1% and less than 0.1%, respectively).

Read the full study here (doi:10.1542/peds.2015-4387).

[email protected]

NEW YORK – A study of an international database of individuals who have had open repair for acute type A aortic dissection (ATAAD) has revealed that in the past 20 years, cardiovascular surgeons have widely embraced valve-sparing procedures, bioprosthetic valves, and cerebral profusion strategies, according to a report here on the latest analysis of the database.

The most telling result is the decline in overall mortality, Santi Trimarchi, MD, PhD, of the University of Milan IRCCS Policlinico San Donato in Italy reported on behalf of the International Registry of Acute Aortic Dissection (IRAD) Interventional Cohort (IVC). The cohort analyzed surgery techniques and outcomes of 1,732 patients who had open repair from 1996 to 2016, clustering results in three time intervals: 1996-2003; 2004-2009; and 2010-2015.

“We noted in the registry that the overall in-hospital mortality rate was 14.3%, and this mortality decreased over time from 17.5% in the first six-year time span to 12.2% in the last six years,” Dr. Trimarchi said.

Among other trends the study identified are greater reliance on biological vs. mechanical valves, an increase in valve-sparing procedures, and steady use of Bentall procedures throughout the study period. “Operative techniques for redo aortic valve repair have been improving over the time, and that’s why we see more frequent use of biologic valves,” he said at the meeting, sponsored by the American Association for Thoracic Surgery.

“Cerebral profusion management has been widely adopted,” Dr. Trimarchi said. “Also there is an important trend showing an increasing utilization of antegrade cerebral profusion while we see a negative trend of the utilization of retrograde brain protection.”

Dr. Trimarchi attributed the detail the study generated to the survey form sent to the 26 IRAD-IVC sites around the world. The form measures 131 different variables, he said.

“Using this new specific surgical data form, we think we can address some surgical issues and report better data from the IRAD registry results on acute dissection,” he said. “These analyses have shown there have been significant changes in operative strategy over time in terms of managing such patients, and more importantly, a significant decrease in in-hospital mortality was observed in a 20-year time period.”

Dr. Trimarchi disclosed that he has received speaking and consulting fees and research support from W.L. Gore & Associates and Medtronic. IRAD is supported by W.L. Gore, Active Sites, Medtronic, Varbedian Aortic Research Fund, the Hewlett Foundation, the Mardigian Foundation, UM Faculty Group Practice, Terumo, and Ann and Bob Aikens.

NEW YORK – A study of an international database of individuals who have had open repair for acute type A aortic dissection (ATAAD) has revealed that in the past 20 years, cardiovascular surgeons have widely embraced valve-sparing procedures, bioprosthetic valves, and cerebral profusion strategies, according to a report here on the latest analysis of the database.

The most telling result is the decline in overall mortality, Santi Trimarchi, MD, PhD, of the University of Milan IRCCS Policlinico San Donato in Italy reported on behalf of the International Registry of Acute Aortic Dissection (IRAD) Interventional Cohort (IVC). The cohort analyzed surgery techniques and outcomes of 1,732 patients who had open repair from 1996 to 2016, clustering results in three time intervals: 1996-2003; 2004-2009; and 2010-2015.

“We noted in the registry that the overall in-hospital mortality rate was 14.3%, and this mortality decreased over time from 17.5% in the first six-year time span to 12.2% in the last six years,” Dr. Trimarchi said.

Among other trends the study identified are greater reliance on biological vs. mechanical valves, an increase in valve-sparing procedures, and steady use of Bentall procedures throughout the study period. “Operative techniques for redo aortic valve repair have been improving over the time, and that’s why we see more frequent use of biologic valves,” he said at the meeting, sponsored by the American Association for Thoracic Surgery.

“Cerebral profusion management has been widely adopted,” Dr. Trimarchi said. “Also there is an important trend showing an increasing utilization of antegrade cerebral profusion while we see a negative trend of the utilization of retrograde brain protection.”

Dr. Trimarchi attributed the detail the study generated to the survey form sent to the 26 IRAD-IVC sites around the world. The form measures 131 different variables, he said.

“Using this new specific surgical data form, we think we can address some surgical issues and report better data from the IRAD registry results on acute dissection,” he said. “These analyses have shown there have been significant changes in operative strategy over time in terms of managing such patients, and more importantly, a significant decrease in in-hospital mortality was observed in a 20-year time period.”

Dr. Trimarchi disclosed that he has received speaking and consulting fees and research support from W.L. Gore & Associates and Medtronic. IRAD is supported by W.L. Gore, Active Sites, Medtronic, Varbedian Aortic Research Fund, the Hewlett Foundation, the Mardigian Foundation, UM Faculty Group Practice, Terumo, and Ann and Bob Aikens.

NEW YORK – A study of an international database of individuals who have had open repair for acute type A aortic dissection (ATAAD) has revealed that in the past 20 years, cardiovascular surgeons have widely embraced valve-sparing procedures, bioprosthetic valves, and cerebral profusion strategies, according to a report here on the latest analysis of the database.

The most telling result is the decline in overall mortality, Santi Trimarchi, MD, PhD, of the University of Milan IRCCS Policlinico San Donato in Italy reported on behalf of the International Registry of Acute Aortic Dissection (IRAD) Interventional Cohort (IVC). The cohort analyzed surgery techniques and outcomes of 1,732 patients who had open repair from 1996 to 2016, clustering results in three time intervals: 1996-2003; 2004-2009; and 2010-2015.

“We noted in the registry that the overall in-hospital mortality rate was 14.3%, and this mortality decreased over time from 17.5% in the first six-year time span to 12.2% in the last six years,” Dr. Trimarchi said.

Among other trends the study identified are greater reliance on biological vs. mechanical valves, an increase in valve-sparing procedures, and steady use of Bentall procedures throughout the study period. “Operative techniques for redo aortic valve repair have been improving over the time, and that’s why we see more frequent use of biologic valves,” he said at the meeting, sponsored by the American Association for Thoracic Surgery.

“Cerebral profusion management has been widely adopted,” Dr. Trimarchi said. “Also there is an important trend showing an increasing utilization of antegrade cerebral profusion while we see a negative trend of the utilization of retrograde brain protection.”

Dr. Trimarchi attributed the detail the study generated to the survey form sent to the 26 IRAD-IVC sites around the world. The form measures 131 different variables, he said.

“Using this new specific surgical data form, we think we can address some surgical issues and report better data from the IRAD registry results on acute dissection,” he said. “These analyses have shown there have been significant changes in operative strategy over time in terms of managing such patients, and more importantly, a significant decrease in in-hospital mortality was observed in a 20-year time period.”

Dr. Trimarchi disclosed that he has received speaking and consulting fees and research support from W.L. Gore & Associates and Medtronic. IRAD is supported by W.L. Gore, Active Sites, Medtronic, Varbedian Aortic Research Fund, the Hewlett Foundation, the Mardigian Foundation, UM Faculty Group Practice, Terumo, and Ann and Bob Aikens.

The U.S teen birth rate has dropped for another consecutive year, adding to the long-term decline in teen pregnancy, according to a federal report on trends in child health and well being.

©istock/Thinkstock.com

In 2014, the teen birth rate was 11 births per 1,000 girls’ aged 15-17 years, down from 12 per 1,000 in 2013. Racial and ethinic disparities in the teen birth rate have also dropped significantly since 1995 – with the difference between the highest and lowest rates dropping from 55 points in 1995 to 17 points in 2014. But substantial disparities persist.

The report also found that the percentages of 10th and 12th-graders in all racial and ethnic groups who binge-drink were the lowest in 2015 since the report started in 1980. The percentage of uninsured children also declined, falling from 7% in 2013 to 5% in 2014. However, there was no improvement in the rate of childhood obesity. During 2011-2014, 19% of children aged 6-17 years were obese.

The annual report is published by the Federal Interagency Forum on Child and Family Statistics, a working group of 23 federal agencies that collect, analyze and report data on conditions and trends related to child and family well-being. The report tracks 41 health and social indicators.

Read the full 2016 America’s Children Report here.

[email protected]

The U.S teen birth rate has dropped for another consecutive year, adding to the long-term decline in teen pregnancy, according to a federal report on trends in child health and well being.

©istock/Thinkstock.com

In 2014, the teen birth rate was 11 births per 1,000 girls’ aged 15-17 years, down from 12 per 1,000 in 2013. Racial and ethinic disparities in the teen birth rate have also dropped significantly since 1995 – with the difference between the highest and lowest rates dropping from 55 points in 1995 to 17 points in 2014. But substantial disparities persist.

The report also found that the percentages of 10th and 12th-graders in all racial and ethnic groups who binge-drink were the lowest in 2015 since the report started in 1980. The percentage of uninsured children also declined, falling from 7% in 2013 to 5% in 2014. However, there was no improvement in the rate of childhood obesity. During 2011-2014, 19% of children aged 6-17 years were obese.

The annual report is published by the Federal Interagency Forum on Child and Family Statistics, a working group of 23 federal agencies that collect, analyze and report data on conditions and trends related to child and family well-being. The report tracks 41 health and social indicators.

Read the full 2016 America’s Children Report here.

[email protected]

The U.S teen birth rate has dropped for another consecutive year, adding to the long-term decline in teen pregnancy, according to a federal report on trends in child health and well being.

©istock/Thinkstock.com

In 2014, the teen birth rate was 11 births per 1,000 girls’ aged 15-17 years, down from 12 per 1,000 in 2013. Racial and ethinic disparities in the teen birth rate have also dropped significantly since 1995 – with the difference between the highest and lowest rates dropping from 55 points in 1995 to 17 points in 2014. But substantial disparities persist.

The report also found that the percentages of 10th and 12th-graders in all racial and ethnic groups who binge-drink were the lowest in 2015 since the report started in 1980. The percentage of uninsured children also declined, falling from 7% in 2013 to 5% in 2014. However, there was no improvement in the rate of childhood obesity. During 2011-2014, 19% of children aged 6-17 years were obese.

The annual report is published by the Federal Interagency Forum on Child and Family Statistics, a working group of 23 federal agencies that collect, analyze and report data on conditions and trends related to child and family well-being. The report tracks 41 health and social indicators.

Read the full 2016 America’s Children Report here.

[email protected]

NEW YORK – Mastery is the product of repetition, and it has long been taken for granted that surgeons and centers that perform a high volume of an operation will have better results than those who don’t do the operation as often, but a study out of the United Kingdom has determined just how much better high-volume centers are when it comes to repair of acute type A aortic dissection (ATAD) – and what the in-hospital mortality odds ratio is for lower-volume surgeons.

Specifically, that odds ratio is 1.64 (P = .030), Mohamad Bashir, MD, PhD, MRCS, a research fellow at Liverpool Heart and Chest Hospital, said in reporting early results of the study here. Lower-volume surgeons had worse outcomes in 12 of 14 different operative metrics the study evaluated, most notably in-hospital mortality: 20.2% for lower-volume surgeons vs. 15.2% for higher-volume surgeons. “There is an initiative in the U.K. to change the trend,” Dr. Bashir said. Full study results will be published in an upcoming issue of BMJ, he said.

“In-hospital mortality for surgeons who operate on 20 or more procedures is very good at 13.2%, and the same follows for 90-day mortality, one-year mortality and three-year mortality,” Dr. Bashir said.

The study evaluated 1,386 ATAD procedures in the National Institute for Cardiovascular Outcomes Research database by 218 different cardiac surgeons at 33 different hospitals in England and Wales from April 2007 to March 2013. That would make the average number of procedures per surgeon 6.4, Dr. Bashir said, but a closer look at each surgeon’s case load reveals some disconcerting trends: almost 80% of the surgeons performed fewer than 10 ATAD repairs in the 6-year span of the study, and 34 surgeons, or about 15%, just did a single procedure in that time. The highest-volume surgeon did 32 procedures. The minimum hospital volume was 8 ATAD operations and the maximum was 103.

The study stratified lower- and higher-volume surgeon groups by characteristics of the patients they operated on. “The differences between these two groups are pretty interesting because we noticed that the lower-volume surgeons are actually operating on patients who are diabetic, who are smokers, who use inotropic support prior to anesthesia and who also have an injection fraction that is significant,” Dr. Bashir said.

In drilling down into those characteristics, people with diabetes made up 6% of the lower-volume surgeons’ cases vs. 3.1% of the higher-volume surgeons’ cases, despite an almost 50-50 split in share of procedures between the two surgeon groups. Current smokers comprised 20.5% of the lower-volume surgeons’ patients vs. 15.5% of their high-volume counterparts’ patients. Operative characteristics in terms of urgency of surgery were similar between the two groups. However Dr. Bashir noted, lower-volume surgeons had longer times for cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest.

The study investigators applied a multivariable logistic regression model to determine predictors of in-hospital mortality for ATAD. “The odds ratio (OR) of mortality for lower-volume surgeons is 1.64, which is statistically significant,” Dr. Bashir said. Odds ratios for other predictors are: previous cardiac surgery, 2.51; peripheral vascular disease, 2.15; preoperative cardiogenic shock, 2.05; salvage operation, 5.57; and concomitant coronary artery bypass procedure, 2.98. For 5-year mortality, the odds ratio was 1.37 for the lower-volume surgeons.

Dr. Bashir laid out how the National Health Service can use the study results. “Concentration of expertise and volume to the appropriate surgeons and centers who perform increasingly more work and more complex aortic cases would be required to change the paradigm of acute type A aortic dissection outcomes in the U.K.,” he said. “It is reasonable to suggest that there should be a national standardization mandate and a quality-improvement framework of acute aortic dissection treatment.”

Dr. Bashir had no financial relationships to disclose.

NEW YORK – Mastery is the product of repetition, and it has long been taken for granted that surgeons and centers that perform a high volume of an operation will have better results than those who don’t do the operation as often, but a study out of the United Kingdom has determined just how much better high-volume centers are when it comes to repair of acute type A aortic dissection (ATAD) – and what the in-hospital mortality odds ratio is for lower-volume surgeons.

Specifically, that odds ratio is 1.64 (P = .030), Mohamad Bashir, MD, PhD, MRCS, a research fellow at Liverpool Heart and Chest Hospital, said in reporting early results of the study here. Lower-volume surgeons had worse outcomes in 12 of 14 different operative metrics the study evaluated, most notably in-hospital mortality: 20.2% for lower-volume surgeons vs. 15.2% for higher-volume surgeons. “There is an initiative in the U.K. to change the trend,” Dr. Bashir said. Full study results will be published in an upcoming issue of BMJ, he said.

“In-hospital mortality for surgeons who operate on 20 or more procedures is very good at 13.2%, and the same follows for 90-day mortality, one-year mortality and three-year mortality,” Dr. Bashir said.

The study evaluated 1,386 ATAD procedures in the National Institute for Cardiovascular Outcomes Research database by 218 different cardiac surgeons at 33 different hospitals in England and Wales from April 2007 to March 2013. That would make the average number of procedures per surgeon 6.4, Dr. Bashir said, but a closer look at each surgeon’s case load reveals some disconcerting trends: almost 80% of the surgeons performed fewer than 10 ATAD repairs in the 6-year span of the study, and 34 surgeons, or about 15%, just did a single procedure in that time. The highest-volume surgeon did 32 procedures. The minimum hospital volume was 8 ATAD operations and the maximum was 103.

The study stratified lower- and higher-volume surgeon groups by characteristics of the patients they operated on. “The differences between these two groups are pretty interesting because we noticed that the lower-volume surgeons are actually operating on patients who are diabetic, who are smokers, who use inotropic support prior to anesthesia and who also have an injection fraction that is significant,” Dr. Bashir said.

In drilling down into those characteristics, people with diabetes made up 6% of the lower-volume surgeons’ cases vs. 3.1% of the higher-volume surgeons’ cases, despite an almost 50-50 split in share of procedures between the two surgeon groups. Current smokers comprised 20.5% of the lower-volume surgeons’ patients vs. 15.5% of their high-volume counterparts’ patients. Operative characteristics in terms of urgency of surgery were similar between the two groups. However Dr. Bashir noted, lower-volume surgeons had longer times for cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest.

The study investigators applied a multivariable logistic regression model to determine predictors of in-hospital mortality for ATAD. “The odds ratio (OR) of mortality for lower-volume surgeons is 1.64, which is statistically significant,” Dr. Bashir said. Odds ratios for other predictors are: previous cardiac surgery, 2.51; peripheral vascular disease, 2.15; preoperative cardiogenic shock, 2.05; salvage operation, 5.57; and concomitant coronary artery bypass procedure, 2.98. For 5-year mortality, the odds ratio was 1.37 for the lower-volume surgeons.

Dr. Bashir laid out how the National Health Service can use the study results. “Concentration of expertise and volume to the appropriate surgeons and centers who perform increasingly more work and more complex aortic cases would be required to change the paradigm of acute type A aortic dissection outcomes in the U.K.,” he said. “It is reasonable to suggest that there should be a national standardization mandate and a quality-improvement framework of acute aortic dissection treatment.”

Dr. Bashir had no financial relationships to disclose.

NEW YORK – Mastery is the product of repetition, and it has long been taken for granted that surgeons and centers that perform a high volume of an operation will have better results than those who don’t do the operation as often, but a study out of the United Kingdom has determined just how much better high-volume centers are when it comes to repair of acute type A aortic dissection (ATAD) – and what the in-hospital mortality odds ratio is for lower-volume surgeons.

Specifically, that odds ratio is 1.64 (P = .030), Mohamad Bashir, MD, PhD, MRCS, a research fellow at Liverpool Heart and Chest Hospital, said in reporting early results of the study here. Lower-volume surgeons had worse outcomes in 12 of 14 different operative metrics the study evaluated, most notably in-hospital mortality: 20.2% for lower-volume surgeons vs. 15.2% for higher-volume surgeons. “There is an initiative in the U.K. to change the trend,” Dr. Bashir said. Full study results will be published in an upcoming issue of BMJ, he said.

“In-hospital mortality for surgeons who operate on 20 or more procedures is very good at 13.2%, and the same follows for 90-day mortality, one-year mortality and three-year mortality,” Dr. Bashir said.

The study evaluated 1,386 ATAD procedures in the National Institute for Cardiovascular Outcomes Research database by 218 different cardiac surgeons at 33 different hospitals in England and Wales from April 2007 to March 2013. That would make the average number of procedures per surgeon 6.4, Dr. Bashir said, but a closer look at each surgeon’s case load reveals some disconcerting trends: almost 80% of the surgeons performed fewer than 10 ATAD repairs in the 6-year span of the study, and 34 surgeons, or about 15%, just did a single procedure in that time. The highest-volume surgeon did 32 procedures. The minimum hospital volume was 8 ATAD operations and the maximum was 103.

The study stratified lower- and higher-volume surgeon groups by characteristics of the patients they operated on. “The differences between these two groups are pretty interesting because we noticed that the lower-volume surgeons are actually operating on patients who are diabetic, who are smokers, who use inotropic support prior to anesthesia and who also have an injection fraction that is significant,” Dr. Bashir said.

In drilling down into those characteristics, people with diabetes made up 6% of the lower-volume surgeons’ cases vs. 3.1% of the higher-volume surgeons’ cases, despite an almost 50-50 split in share of procedures between the two surgeon groups. Current smokers comprised 20.5% of the lower-volume surgeons’ patients vs. 15.5% of their high-volume counterparts’ patients. Operative characteristics in terms of urgency of surgery were similar between the two groups. However Dr. Bashir noted, lower-volume surgeons had longer times for cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest.

The study investigators applied a multivariable logistic regression model to determine predictors of in-hospital mortality for ATAD. “The odds ratio (OR) of mortality for lower-volume surgeons is 1.64, which is statistically significant,” Dr. Bashir said. Odds ratios for other predictors are: previous cardiac surgery, 2.51; peripheral vascular disease, 2.15; preoperative cardiogenic shock, 2.05; salvage operation, 5.57; and concomitant coronary artery bypass procedure, 2.98. For 5-year mortality, the odds ratio was 1.37 for the lower-volume surgeons.

Dr. Bashir laid out how the National Health Service can use the study results. “Concentration of expertise and volume to the appropriate surgeons and centers who perform increasingly more work and more complex aortic cases would be required to change the paradigm of acute type A aortic dissection outcomes in the U.K.,” he said. “It is reasonable to suggest that there should be a national standardization mandate and a quality-improvement framework of acute aortic dissection treatment.”

Dr. Bashir had no financial relationships to disclose.

Colorectal cancer screening by a variety of methods is worthwhile and recommended for all adults aged 50-75 years, according to the latest recommendations from the U.S. Preventive Services Task Force. The USPSTF statement and summary of evidence were published in JAMA on June 15.

In addition, the USPSTF recommended selective screening for older adults aged 76-85 years, depending on their health status and screening history.

©KUO CHUN HUNG/Thinkstock

A team of researchers led by Dr. Jennifer S. Lin of Kaiser Permanente in Portland, Ore., reviewed studies on colorectal cancer screening published between Jan.1, 2008, and Dec. 31, 2014, with surveillance continuing through Feb. 23, 2016 (JAMA. 2016 Jun;315:2576-94 [doi: 10.1001/jama.2016.3332]). The USPSTF’s last recommendations on colorectal cancer screening were released in 2008.

“Although CRC screening has a large body of supporting evidence, additional research is still needed to weigh the relative benefits and harms of each test within a program of screening” for average-risk adults, the researchers noted.

The final recommendation statement includes three screening options that carry over from the 2008 guidelines: colonoscopy, sigmoidoscopy, and fecal immunochemical testing (FIT) with occult blood.

Other options now recommended include computed tomographic colonography (CTC), fecal immunochemical tests with DNA (FIT-DNA), guaiac-based fecal occult blood testing (gFOBT), and sigmoidoscopy plus FIT.

Some highlights from the analysis: Four randomized trials including 458,002 patients showed that one-time or two-time screening with flexible sigmoidoscopy was associated with decreased mortality from colorectal cancer, compared with no screening, for an incidence rate ratio of 0.73, the researchers wrote.

In addition, the researchers found that CTC had 73%-98% sensitivity and 89%-91% specificity to detect adenomas 6 mm and larger, compared with colonoscopy in seven studies. However, the risk of harm from low-dose ionizing radiation remains a consideration.

For diagnostic accuracy, colonoscopy showed per-person sensitivity of 89%-98% for adenomas 10 mm or larger, and 75%-93% for adenomas 6 mm or larger, in studies comparing it with CTC or as an adjunct to CTC. However, studies showing applicability to community practices were limited.

Fecal immunochemical tests (FITs) showed sensitivity ranging from 73% to 88% and specificity from 90% to 96%.

Data from five randomized, controlled trials evaluating multiple rounds of biennial screening using gFOBT showed a significant reduction in colorectal cancer mortality, from a relative risk of 0.91 at 19.5 years to a relative risk of 0.78 at 30 years.

Colonoscopy remains the standard by which other tests are assessed, although it has the highest risk of procedural complications, the researchers said. Three new randomized, controlled trials involving screening colonoscopy in average-risk adults scheduled for completion in 2021, 2026, and 2027, may yield more information on incidence and mortality, they added.

The evidence report and review was limited by its focus on average-risk adults; it did not address factors including screening for high-risk adults, availability and access to tests, potential risks of overdiagnosis, and overuse of screening after adenoma detection, the researchers said. In addition, “data are still needed on the differential uptake of and adherence to screening modalities and on continued adherence to repeated rounds of screening and diagnostic follow-up to screening over longer periods,” they said. However, they concluded, “colonoscopy, flexible sigmoidoscopy, CTC, and various stool tests have differing levels of evidence to support their use in CRC screening, ability to detect CRC and precursor lesions, and risk of serious adverse events in average-risk adults.”

The researchers had no relevant financial conflicts to disclose. The research was supported by the Agency for Healthcare Research and Quality under a contract with the U.S. Preventive Services Task Force.

The final recommendation statement is available online at USPSTF.

Colorectal cancer screening by a variety of methods is worthwhile and recommended for all adults aged 50-75 years, according to the latest recommendations from the U.S. Preventive Services Task Force. The USPSTF statement and summary of evidence were published in JAMA on June 15.

In addition, the USPSTF recommended selective screening for older adults aged 76-85 years, depending on their health status and screening history.

©KUO CHUN HUNG/Thinkstock

A team of researchers led by Dr. Jennifer S. Lin of Kaiser Permanente in Portland, Ore., reviewed studies on colorectal cancer screening published between Jan.1, 2008, and Dec. 31, 2014, with surveillance continuing through Feb. 23, 2016 (JAMA. 2016 Jun;315:2576-94 [doi: 10.1001/jama.2016.3332]). The USPSTF’s last recommendations on colorectal cancer screening were released in 2008.

“Although CRC screening has a large body of supporting evidence, additional research is still needed to weigh the relative benefits and harms of each test within a program of screening” for average-risk adults, the researchers noted.

The final recommendation statement includes three screening options that carry over from the 2008 guidelines: colonoscopy, sigmoidoscopy, and fecal immunochemical testing (FIT) with occult blood.

Other options now recommended include computed tomographic colonography (CTC), fecal immunochemical tests with DNA (FIT-DNA), guaiac-based fecal occult blood testing (gFOBT), and sigmoidoscopy plus FIT.

Some highlights from the analysis: Four randomized trials including 458,002 patients showed that one-time or two-time screening with flexible sigmoidoscopy was associated with decreased mortality from colorectal cancer, compared with no screening, for an incidence rate ratio of 0.73, the researchers wrote.

In addition, the researchers found that CTC had 73%-98% sensitivity and 89%-91% specificity to detect adenomas 6 mm and larger, compared with colonoscopy in seven studies. However, the risk of harm from low-dose ionizing radiation remains a consideration.

For diagnostic accuracy, colonoscopy showed per-person sensitivity of 89%-98% for adenomas 10 mm or larger, and 75%-93% for adenomas 6 mm or larger, in studies comparing it with CTC or as an adjunct to CTC. However, studies showing applicability to community practices were limited.

Fecal immunochemical tests (FITs) showed sensitivity ranging from 73% to 88% and specificity from 90% to 96%.

Data from five randomized, controlled trials evaluating multiple rounds of biennial screening using gFOBT showed a significant reduction in colorectal cancer mortality, from a relative risk of 0.91 at 19.5 years to a relative risk of 0.78 at 30 years.

Colonoscopy remains the standard by which other tests are assessed, although it has the highest risk of procedural complications, the researchers said. Three new randomized, controlled trials involving screening colonoscopy in average-risk adults scheduled for completion in 2021, 2026, and 2027, may yield more information on incidence and mortality, they added.

The evidence report and review was limited by its focus on average-risk adults; it did not address factors including screening for high-risk adults, availability and access to tests, potential risks of overdiagnosis, and overuse of screening after adenoma detection, the researchers said. In addition, “data are still needed on the differential uptake of and adherence to screening modalities and on continued adherence to repeated rounds of screening and diagnostic follow-up to screening over longer periods,” they said. However, they concluded, “colonoscopy, flexible sigmoidoscopy, CTC, and various stool tests have differing levels of evidence to support their use in CRC screening, ability to detect CRC and precursor lesions, and risk of serious adverse events in average-risk adults.”

The researchers had no relevant financial conflicts to disclose. The research was supported by the Agency for Healthcare Research and Quality under a contract with the U.S. Preventive Services Task Force.

The final recommendation statement is available online at USPSTF.

Colorectal cancer screening by a variety of methods is worthwhile and recommended for all adults aged 50-75 years, according to the latest recommendations from the U.S. Preventive Services Task Force. The USPSTF statement and summary of evidence were published in JAMA on June 15.

In addition, the USPSTF recommended selective screening for older adults aged 76-85 years, depending on their health status and screening history.

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A team of researchers led by Dr. Jennifer S. Lin of Kaiser Permanente in Portland, Ore., reviewed studies on colorectal cancer screening published between Jan.1, 2008, and Dec. 31, 2014, with surveillance continuing through Feb. 23, 2016 (JAMA. 2016 Jun;315:2576-94 [doi: 10.1001/jama.2016.3332]). The USPSTF’s last recommendations on colorectal cancer screening were released in 2008.

“Although CRC screening has a large body of supporting evidence, additional research is still needed to weigh the relative benefits and harms of each test within a program of screening” for average-risk adults, the researchers noted.

The final recommendation statement includes three screening options that carry over from the 2008 guidelines: colonoscopy, sigmoidoscopy, and fecal immunochemical testing (FIT) with occult blood.

Other options now recommended include computed tomographic colonography (CTC), fecal immunochemical tests with DNA (FIT-DNA), guaiac-based fecal occult blood testing (gFOBT), and sigmoidoscopy plus FIT.

Some highlights from the analysis: Four randomized trials including 458,002 patients showed that one-time or two-time screening with flexible sigmoidoscopy was associated with decreased mortality from colorectal cancer, compared with no screening, for an incidence rate ratio of 0.73, the researchers wrote.

In addition, the researchers found that CTC had 73%-98% sensitivity and 89%-91% specificity to detect adenomas 6 mm and larger, compared with colonoscopy in seven studies. However, the risk of harm from low-dose ionizing radiation remains a consideration.

For diagnostic accuracy, colonoscopy showed per-person sensitivity of 89%-98% for adenomas 10 mm or larger, and 75%-93% for adenomas 6 mm or larger, in studies comparing it with CTC or as an adjunct to CTC. However, studies showing applicability to community practices were limited.

Fecal immunochemical tests (FITs) showed sensitivity ranging from 73% to 88% and specificity from 90% to 96%.

Data from five randomized, controlled trials evaluating multiple rounds of biennial screening using gFOBT showed a significant reduction in colorectal cancer mortality, from a relative risk of 0.91 at 19.5 years to a relative risk of 0.78 at 30 years.

Colonoscopy remains the standard by which other tests are assessed, although it has the highest risk of procedural complications, the researchers said. Three new randomized, controlled trials involving screening colonoscopy in average-risk adults scheduled for completion in 2021, 2026, and 2027, may yield more information on incidence and mortality, they added.

The evidence report and review was limited by its focus on average-risk adults; it did not address factors including screening for high-risk adults, availability and access to tests, potential risks of overdiagnosis, and overuse of screening after adenoma detection, the researchers said. In addition, “data are still needed on the differential uptake of and adherence to screening modalities and on continued adherence to repeated rounds of screening and diagnostic follow-up to screening over longer periods,” they said. However, they concluded, “colonoscopy, flexible sigmoidoscopy, CTC, and various stool tests have differing levels of evidence to support their use in CRC screening, ability to detect CRC and precursor lesions, and risk of serious adverse events in average-risk adults.”

The researchers had no relevant financial conflicts to disclose. The research was supported by the Agency for Healthcare Research and Quality under a contract with the U.S. Preventive Services Task Force.

The final recommendation statement is available online at USPSTF.