Every other year, SHM’s practice analysis subcommittee invites all U.S. hospital medicine groups to participate in the State of Hospital Medicine (SOHM) survey. Your responses generate the authoritative report on how today’s hospital medicine groups are organized, scheduled, funded, compensated, staffed, and much more. After months of refining and updating, the survey opened on Jan. 11. The time has arrived for you to respond to this critical survey!

Empower Your Hospitalist Program

Hospital medicine has seen the most dramatic growth and evolution of any specialty in the last two decades. Although all practices innovate in response to shifting demands, leaders and hospitalists alike need to understand how the frontrunners in this dynamic field have adapted. The SoHM report summarizes thousands of data points about the latest trends in hospital medicine practice design and productivity.

Hospitalist group leaders depend on this information to draw comparisons against national benchmarks, both for improvement and as a frame of reference for demonstrating the value your group provides to your hospital. However, the report is only as good as the number and quality of the responses to the survey.

How To Get Engaged

Responding to the survey is straightforward through the web-based questionnaire, and only one response is needed from each group. The survey does require some modest preparation to look up such practice characteristics as CPT code distribution, total RVU generation, and average number of shifts per FTE. For many groups, a hospitalist and a practice manager can collaborate to answer all of the questions accurately. If you haven’t already, take some basic steps to prepare:

1. Discuss the survey at your next group meeting and advocate for responding.
2. Determine who will complete the survey on behalf of your group.
3. Visit www.hospitalmedicine.org/survey and download the survey instrument and instructions, share them with the lead respondent for your group.
4. Submit your responses by March 11.

Of note, you’ll also want to participate in the Medical Group Management Association (MGMA) survey, as well. SHM licenses key portions of the SoHM report from MGMA, such as provider compensation, so the complete report depends on having great responses to both instruments.

Why Participate?

First, hospitalist groups that respond to the Survey will get a FREE copy of the report. Have you wondered things like:

• “How many groups are using a scheduling model other than 7-on, 7-off?”
• “What percentage of groups staff an observation unit?”
• “Are hospitalists groups taking on new roles in Accountable Care Organizations (ACOs)?”
• “How does compensation differ for providers who see children or are in academics?”

If so, you’ll have those answers at your fingertips and a whole lot more.

Second, you’ll have the satisfaction of knowing that you helped to make the SoHM report the indispensable tool upon which group leaders everywhere depend. The survey is anonymous, but respondents will know that the report presents data on the most relevant HM group of all—your own! Don’t wait.

Participate today at www.hospitalmedicine.org/survey. TH

Dr. White is assistant professor of medicine at the University of Washington and group director at the University of Washington Medical Center in Seattle, Wash.

Every other year, SHM’s practice analysis subcommittee invites all U.S. hospital medicine groups to participate in the State of Hospital Medicine (SOHM) survey. Your responses generate the authoritative report on how today’s hospital medicine groups are organized, scheduled, funded, compensated, staffed, and much more. After months of refining and updating, the survey opened on Jan. 11. The time has arrived for you to respond to this critical survey!

Empower Your Hospitalist Program

Hospital medicine has seen the most dramatic growth and evolution of any specialty in the last two decades. Although all practices innovate in response to shifting demands, leaders and hospitalists alike need to understand how the frontrunners in this dynamic field have adapted. The SoHM report summarizes thousands of data points about the latest trends in hospital medicine practice design and productivity.

Hospitalist group leaders depend on this information to draw comparisons against national benchmarks, both for improvement and as a frame of reference for demonstrating the value your group provides to your hospital. However, the report is only as good as the number and quality of the responses to the survey.

How To Get Engaged

Responding to the survey is straightforward through the web-based questionnaire, and only one response is needed from each group. The survey does require some modest preparation to look up such practice characteristics as CPT code distribution, total RVU generation, and average number of shifts per FTE. For many groups, a hospitalist and a practice manager can collaborate to answer all of the questions accurately. If you haven’t already, take some basic steps to prepare:

1. Discuss the survey at your next group meeting and advocate for responding.
2. Determine who will complete the survey on behalf of your group.
3. Visit www.hospitalmedicine.org/survey and download the survey instrument and instructions, share them with the lead respondent for your group.
4. Submit your responses by March 11.

Of note, you’ll also want to participate in the Medical Group Management Association (MGMA) survey, as well. SHM licenses key portions of the SoHM report from MGMA, such as provider compensation, so the complete report depends on having great responses to both instruments.

Why Participate?

First, hospitalist groups that respond to the Survey will get a FREE copy of the report. Have you wondered things like:

• “How many groups are using a scheduling model other than 7-on, 7-off?”
• “What percentage of groups staff an observation unit?”
• “Are hospitalists groups taking on new roles in Accountable Care Organizations (ACOs)?”
• “How does compensation differ for providers who see children or are in academics?”

If so, you’ll have those answers at your fingertips and a whole lot more.

Second, you’ll have the satisfaction of knowing that you helped to make the SoHM report the indispensable tool upon which group leaders everywhere depend. The survey is anonymous, but respondents will know that the report presents data on the most relevant HM group of all—your own! Don’t wait.

Participate today at www.hospitalmedicine.org/survey. TH

Dr. White is assistant professor of medicine at the University of Washington and group director at the University of Washington Medical Center in Seattle, Wash.

Every other year, SHM’s practice analysis subcommittee invites all U.S. hospital medicine groups to participate in the State of Hospital Medicine (SOHM) survey. Your responses generate the authoritative report on how today’s hospital medicine groups are organized, scheduled, funded, compensated, staffed, and much more. After months of refining and updating, the survey opened on Jan. 11. The time has arrived for you to respond to this critical survey!

Empower Your Hospitalist Program

Hospital medicine has seen the most dramatic growth and evolution of any specialty in the last two decades. Although all practices innovate in response to shifting demands, leaders and hospitalists alike need to understand how the frontrunners in this dynamic field have adapted. The SoHM report summarizes thousands of data points about the latest trends in hospital medicine practice design and productivity.

Hospitalist group leaders depend on this information to draw comparisons against national benchmarks, both for improvement and as a frame of reference for demonstrating the value your group provides to your hospital. However, the report is only as good as the number and quality of the responses to the survey.

How To Get Engaged

Responding to the survey is straightforward through the web-based questionnaire, and only one response is needed from each group. The survey does require some modest preparation to look up such practice characteristics as CPT code distribution, total RVU generation, and average number of shifts per FTE. For many groups, a hospitalist and a practice manager can collaborate to answer all of the questions accurately. If you haven’t already, take some basic steps to prepare:

1. Discuss the survey at your next group meeting and advocate for responding.
2. Determine who will complete the survey on behalf of your group.
3. Visit www.hospitalmedicine.org/survey and download the survey instrument and instructions, share them with the lead respondent for your group.
4. Submit your responses by March 11.

Of note, you’ll also want to participate in the Medical Group Management Association (MGMA) survey, as well. SHM licenses key portions of the SoHM report from MGMA, such as provider compensation, so the complete report depends on having great responses to both instruments.

Why Participate?

First, hospitalist groups that respond to the Survey will get a FREE copy of the report. Have you wondered things like:

• “How many groups are using a scheduling model other than 7-on, 7-off?”
• “What percentage of groups staff an observation unit?”
• “Are hospitalists groups taking on new roles in Accountable Care Organizations (ACOs)?”
• “How does compensation differ for providers who see children or are in academics?”

If so, you’ll have those answers at your fingertips and a whole lot more.

Second, you’ll have the satisfaction of knowing that you helped to make the SoHM report the indispensable tool upon which group leaders everywhere depend. The survey is anonymous, but respondents will know that the report presents data on the most relevant HM group of all—your own! Don’t wait.

Participate today at www.hospitalmedicine.org/survey. TH

Dr. White is assistant professor of medicine at the University of Washington and group director at the University of Washington Medical Center in Seattle, Wash.

Doctor examines patient

in the intensive care unit

A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.

However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.

The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.

The research was published in JAMA.

Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.

The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.

The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.

In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.

The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.

In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).

Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.

The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification.

Doctor examines patient

in the intensive care unit

A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.

However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.

The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.

The research was published in JAMA.

Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.

The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.

The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.

In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.

The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.

In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).

Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.

The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification.

Doctor examines patient

in the intensive care unit

A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.

However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.

The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.

The research was published in JAMA.

Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.

The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.

The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.

In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.

The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.

In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).

Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.

The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.

The drug was granted priority review for this indication as well.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).

Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.

The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.

However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.

The drug was granted priority review for this indication as well.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).

Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.

The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.

However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.

The drug was granted priority review for this indication as well.

Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).

Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.

The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.

However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.

Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.

Doctor and child

Photo by Matthew Lester

A single-center, retrospective study has revealed an association between obesity and venous thromboembolism (VTE) in children and adolescents.

While obesity is a well-established risk factor for VTE in adults, previous studies in pediatric populations have yielded mixed results.

The new study, however, showed that obesity, as determined by body mass index (BMI), was a statistically significant predictor of VTE in juveniles.

The research was published in Hospital Pediatrics.

“This is important because the incidence of pediatric VTE has increased dramatically over the last 20 years, and childhood obesity remains highly prevalent in the United States,” said study author Elizabeth Halvorson, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

For this study, she and her colleagues conducted a retrospective chart review of inpatients at Wake Forest Baptist’s Brenner Children’s Hospital between January 2000 and September 2012.

The researchers identified 88 patients, ages 2 to 18, who had confirmed cases of VTE. The team compared these patients to control subjects (2 controls per case) matched by age, gender, and the presence of a central venous catheter.

Of the 88 patients with VTE, 33 (37.5%) were obese, although most of them had known risk factors for VTE in addition to obesity.

In univariate analysis, the researchers found a statistically significant association between VTE and obesity, or increased BMI z score (P=0.002).

In a multivariate analysis, obesity remained a significant predictor of VTE. The odds ratio (OR) was 3.1 (P=0.007).

Other factors were significant predictors of VTE as well, including bacteremia (OR: 4.9; P=0.02), a stay in the intensive care unit (OR: 2.5; P=0.02), and the use of oral contraceptives (OR: 17.4; P<0.001).

“Our study presents data from a single institution with a relatively small sample size,” Dr Halvorson noted. “But it does demonstrate an association between obesity and VTE in children, which should be explored further in larger future studies.”

Doctor and child

Photo by Matthew Lester

A single-center, retrospective study has revealed an association between obesity and venous thromboembolism (VTE) in children and adolescents.

While obesity is a well-established risk factor for VTE in adults, previous studies in pediatric populations have yielded mixed results.

The new study, however, showed that obesity, as determined by body mass index (BMI), was a statistically significant predictor of VTE in juveniles.

The research was published in Hospital Pediatrics.

“This is important because the incidence of pediatric VTE has increased dramatically over the last 20 years, and childhood obesity remains highly prevalent in the United States,” said study author Elizabeth Halvorson, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

For this study, she and her colleagues conducted a retrospective chart review of inpatients at Wake Forest Baptist’s Brenner Children’s Hospital between January 2000 and September 2012.

The researchers identified 88 patients, ages 2 to 18, who had confirmed cases of VTE. The team compared these patients to control subjects (2 controls per case) matched by age, gender, and the presence of a central venous catheter.

Of the 88 patients with VTE, 33 (37.5%) were obese, although most of them had known risk factors for VTE in addition to obesity.

In univariate analysis, the researchers found a statistically significant association between VTE and obesity, or increased BMI z score (P=0.002).

In a multivariate analysis, obesity remained a significant predictor of VTE. The odds ratio (OR) was 3.1 (P=0.007).

Other factors were significant predictors of VTE as well, including bacteremia (OR: 4.9; P=0.02), a stay in the intensive care unit (OR: 2.5; P=0.02), and the use of oral contraceptives (OR: 17.4; P<0.001).

“Our study presents data from a single institution with a relatively small sample size,” Dr Halvorson noted. “But it does demonstrate an association between obesity and VTE in children, which should be explored further in larger future studies.”

Doctor and child

Photo by Matthew Lester

A single-center, retrospective study has revealed an association between obesity and venous thromboembolism (VTE) in children and adolescents.

While obesity is a well-established risk factor for VTE in adults, previous studies in pediatric populations have yielded mixed results.

The new study, however, showed that obesity, as determined by body mass index (BMI), was a statistically significant predictor of VTE in juveniles.

The research was published in Hospital Pediatrics.

“This is important because the incidence of pediatric VTE has increased dramatically over the last 20 years, and childhood obesity remains highly prevalent in the United States,” said study author Elizabeth Halvorson, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

For this study, she and her colleagues conducted a retrospective chart review of inpatients at Wake Forest Baptist’s Brenner Children’s Hospital between January 2000 and September 2012.

The researchers identified 88 patients, ages 2 to 18, who had confirmed cases of VTE. The team compared these patients to control subjects (2 controls per case) matched by age, gender, and the presence of a central venous catheter.

Of the 88 patients with VTE, 33 (37.5%) were obese, although most of them had known risk factors for VTE in addition to obesity.

In univariate analysis, the researchers found a statistically significant association between VTE and obesity, or increased BMI z score (P=0.002).

In a multivariate analysis, obesity remained a significant predictor of VTE. The odds ratio (OR) was 3.1 (P=0.007).

Other factors were significant predictors of VTE as well, including bacteremia (OR: 4.9; P=0.02), a stay in the intensive care unit (OR: 2.5; P=0.02), and the use of oral contraceptives (OR: 17.4; P<0.001).

“Our study presents data from a single institution with a relatively small sample size,” Dr Halvorson noted. “But it does demonstrate an association between obesity and VTE in children, which should be explored further in larger future studies.”

Ben Shields, PhD, (left)

and Matt McCormack, PhD

Photo courtesy of the

Walter and Eliza Hall

Institute of Medical Research

Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).

Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.

Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.

“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”

Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.

However, Hhex was not required for normal myelopoiesis.

“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.

“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”

Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.

They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.

“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.

“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”

Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.

“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.

“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”

Ben Shields, PhD, (left)

and Matt McCormack, PhD

Photo courtesy of the

Walter and Eliza Hall

Institute of Medical Research

Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).

Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.

Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.

“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”

Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.

However, Hhex was not required for normal myelopoiesis.

“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.

“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”

Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.

They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.

“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.

“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”

Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.

“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.

“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”

Ben Shields, PhD, (left)

and Matt McCormack, PhD

Photo courtesy of the

Walter and Eliza Hall

Institute of Medical Research

Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).

Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.

Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.

“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”

Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.

However, Hhex was not required for normal myelopoiesis.

“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.

“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”

Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.

They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.

“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.

“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”

Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.

“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.

“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”

Certain cases of female infertility appear to be caused by mutations in the TUBB8 gene that impair microtubule behavior and meiotic spindle assembly, thus preventing oocyte maturation, according to a report published online Jan. 20 in the New England Journal of Medicine.

The findings from a series of genetic analyses “provide the basis for developing diagnostic tools” to identify women who carry these mutations, and also point the way to as-yet undiscovered genetic mutations that also contribute to the arrest of oocyte maturation, wrote Ruizhi Feng, Ph.D., of State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, and his associates.

©SilverV/Thinkstock.com

Immature oocytes are arrested at a phase of development before complete meiosis occurs. Among women seeking in vitro fertilization “it is common for some oocytes to remain immature after ovarian stimulation and administration of human chorionic gonadotropin, but complete arrest of oocyte maturation has been reported in only a few women, and nothing is known about the genetic cause of this phenotype,” they noted.

The investigators identified a four-generation family affected with a rare pattern of inheritance of female infertility, which was found to stem from complete oocyte maturation arrest. They sequenced the exomes of three affected and two unaffected women in the family. All the affected women, but none of the unaffected women, carried a mutation in the TUBB8 gene that encodes for a tubulin isotope. The researchers then found six other TUBB8 mutations (all paternally transmitted) in seven women from four other families with similar oocyte maturation arrest, as well as de novo mutations in two women from two additional families. All of the oocytes assessed either had abnormal spindles or no detectable spindles.

The investigators hypothesized that TUBB8 influences the self-organization of microtubules, and thus meiotic spindle assembly and chromosome orientation, in oocytes. Further analyses confirmed this and showed that the mutations affected tubulin heterodimer folding and assembly in vitro, caused “a spectrum of striking microtubule phenotypes” in cultured HeLa cells, and markedly impaired microtubule dynamics in in-vivo yeast colonies (N Engl J Med 2016;374:223-32. doi:10.1056/NEJMoa1510791).

Finally, to establish a causal relationship between the TUBB8 mutations and infertility, the investigators introduced them into mouse and human oocytes. The TUBB8 mutations caused maturation defects “that precisely mimic the infertility phenotype,” while nonmutated TUBB8 did not, they reported.

“We conclude from these observations that mutations in TUBB8 cause oocyte maturation arrest and that TUBB8 has a key role in meiotic spindle assembly and maturation in human oocytes,” Dr. Feng and his associates wrote.

The National Basic Research Program of China, the Shanghai Key Scientific Research Program, the National Natural Science Foundation of China, the 111 Project, and the U.S. National Institutes of Health supported the study. Dr. Feng and his associates reported having no conflicts of interest.

Certain cases of female infertility appear to be caused by mutations in the TUBB8 gene that impair microtubule behavior and meiotic spindle assembly, thus preventing oocyte maturation, according to a report published online Jan. 20 in the New England Journal of Medicine.

The findings from a series of genetic analyses “provide the basis for developing diagnostic tools” to identify women who carry these mutations, and also point the way to as-yet undiscovered genetic mutations that also contribute to the arrest of oocyte maturation, wrote Ruizhi Feng, Ph.D., of State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, and his associates.

©SilverV/Thinkstock.com

Immature oocytes are arrested at a phase of development before complete meiosis occurs. Among women seeking in vitro fertilization “it is common for some oocytes to remain immature after ovarian stimulation and administration of human chorionic gonadotropin, but complete arrest of oocyte maturation has been reported in only a few women, and nothing is known about the genetic cause of this phenotype,” they noted.

The investigators identified a four-generation family affected with a rare pattern of inheritance of female infertility, which was found to stem from complete oocyte maturation arrest. They sequenced the exomes of three affected and two unaffected women in the family. All the affected women, but none of the unaffected women, carried a mutation in the TUBB8 gene that encodes for a tubulin isotope. The researchers then found six other TUBB8 mutations (all paternally transmitted) in seven women from four other families with similar oocyte maturation arrest, as well as de novo mutations in two women from two additional families. All of the oocytes assessed either had abnormal spindles or no detectable spindles.

The investigators hypothesized that TUBB8 influences the self-organization of microtubules, and thus meiotic spindle assembly and chromosome orientation, in oocytes. Further analyses confirmed this and showed that the mutations affected tubulin heterodimer folding and assembly in vitro, caused “a spectrum of striking microtubule phenotypes” in cultured HeLa cells, and markedly impaired microtubule dynamics in in-vivo yeast colonies (N Engl J Med 2016;374:223-32. doi:10.1056/NEJMoa1510791).

Finally, to establish a causal relationship between the TUBB8 mutations and infertility, the investigators introduced them into mouse and human oocytes. The TUBB8 mutations caused maturation defects “that precisely mimic the infertility phenotype,” while nonmutated TUBB8 did not, they reported.

“We conclude from these observations that mutations in TUBB8 cause oocyte maturation arrest and that TUBB8 has a key role in meiotic spindle assembly and maturation in human oocytes,” Dr. Feng and his associates wrote.

The National Basic Research Program of China, the Shanghai Key Scientific Research Program, the National Natural Science Foundation of China, the 111 Project, and the U.S. National Institutes of Health supported the study. Dr. Feng and his associates reported having no conflicts of interest.

Certain cases of female infertility appear to be caused by mutations in the TUBB8 gene that impair microtubule behavior and meiotic spindle assembly, thus preventing oocyte maturation, according to a report published online Jan. 20 in the New England Journal of Medicine.

The findings from a series of genetic analyses “provide the basis for developing diagnostic tools” to identify women who carry these mutations, and also point the way to as-yet undiscovered genetic mutations that also contribute to the arrest of oocyte maturation, wrote Ruizhi Feng, Ph.D., of State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, and his associates.

©SilverV/Thinkstock.com

Immature oocytes are arrested at a phase of development before complete meiosis occurs. Among women seeking in vitro fertilization “it is common for some oocytes to remain immature after ovarian stimulation and administration of human chorionic gonadotropin, but complete arrest of oocyte maturation has been reported in only a few women, and nothing is known about the genetic cause of this phenotype,” they noted.

The investigators identified a four-generation family affected with a rare pattern of inheritance of female infertility, which was found to stem from complete oocyte maturation arrest. They sequenced the exomes of three affected and two unaffected women in the family. All the affected women, but none of the unaffected women, carried a mutation in the TUBB8 gene that encodes for a tubulin isotope. The researchers then found six other TUBB8 mutations (all paternally transmitted) in seven women from four other families with similar oocyte maturation arrest, as well as de novo mutations in two women from two additional families. All of the oocytes assessed either had abnormal spindles or no detectable spindles.

The investigators hypothesized that TUBB8 influences the self-organization of microtubules, and thus meiotic spindle assembly and chromosome orientation, in oocytes. Further analyses confirmed this and showed that the mutations affected tubulin heterodimer folding and assembly in vitro, caused “a spectrum of striking microtubule phenotypes” in cultured HeLa cells, and markedly impaired microtubule dynamics in in-vivo yeast colonies (N Engl J Med 2016;374:223-32. doi:10.1056/NEJMoa1510791).

Finally, to establish a causal relationship between the TUBB8 mutations and infertility, the investigators introduced them into mouse and human oocytes. The TUBB8 mutations caused maturation defects “that precisely mimic the infertility phenotype,” while nonmutated TUBB8 did not, they reported.

“We conclude from these observations that mutations in TUBB8 cause oocyte maturation arrest and that TUBB8 has a key role in meiotic spindle assembly and maturation in human oocytes,” Dr. Feng and his associates wrote.

The National Basic Research Program of China, the Shanghai Key Scientific Research Program, the National Natural Science Foundation of China, the 111 Project, and the U.S. National Institutes of Health supported the study. Dr. Feng and his associates reported having no conflicts of interest.

A biomarker for which a screening test is already available – lack of CDX2 expression – appears to identify the approximately 20% of stage II and 50% of stage III colon cancers that are at high risk of recurrence and would benefit from adjuvant chemotherapy, according to a report published online Jan. 21 in the New England Journal of Medicine.

Distinguishing the high-risk tumors from those unlikely to recur or progress would allow some patients to opt for adjuvant chemotherapy that has been shown to significantly raise the rates of overall and disease-free survival. At present, almost all patients with stage II colon cancer are treated using surgery alone, said Dr. Piero Dalerba of the Herbert Irving Comprehensive Cancer Center and the department of pathology and cell biology at Columbia University, New York, and his associates.

The investigators used a bioinformatics approach to search for biomarkers that would identify the most aggressive colon cancers: undifferentiated tumors characterized by immature, stem-like colonic epithelial cells and depleted of more mature cells. They focused on biomarkers for which clinical diagnostic tests are already available, to facilitate use in real-world clinical practice. Their search through 2,329 colon gene-expression array experiments found that when tumors do not express one particular protein, homeobox transcription factor CDX2, “a master regulator of intestinal development and oncogenesis” that is highly specifically expressed in intestinal epithelium, those tumors tend to have aggressive features such as advanced stage, vascular invasion, and BRAF mutation.

Survival outcomes were then compared in a discovery data set of 466 patients. The 5-year disease-free survival rate was significantly lower, at 41%, among the 32 patients who had CDX2-negative tumors than the 74% survival rate among the 434 patients with CDX2-positive tumors. The hazard ratio for disease recurrence among patients with CDX2-negative vs. CDX2-positive tumors was 2.73, Dr. Dalerba and his associates said (N Engl J Med. 2016 Jan 21. doi:10.1056/NEJMoa1506597).

The investigators confirmed these findings in a separate validation data set of 366 patients, of whom 48 had CDX2-negative and 318 had CDX2-positive tumors. Five-year disease-free survival (48% vs. 71%), overall survival (33% vs. 59%), and disease-specific survival (45% vs. 72%) were significantly lower with CDX2-negative tumors, and the HR for disease recurrence was 2.42.

To determine whether adjuvant chemotherapy would improve survival outcomes in patients with CDX2-negative tumors, the researchers assessed outcomes in an expanded dataset of 669 patients with stage II and 1,228 patients with stage III colon cancer. They confirmed that among patients with stage II CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (91%) than did those who didn’t receive adjuvant chemotherapy (56%). Similarly, among patients with stage III CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (74%) than those who did not receive adjuvant chemotherapy (37%).

This survival benefit was independent of many known risk factors, including tumor grade, they noted.

These results must be replicated in future prospective studies, because this study’s design was retrospective and exploratory, Dr. Dalerba and his associates added.

This work was supported by the National Comprehensive Cancer Network, the National Institutes of Health, Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, the California Institute for Regenerative Medicine, the U.S. Department of Defense, the Bladder Cancer Advocacy Network, and BD Biosciences. Dr. Dalerba reported ties to Quanticel Pharmaceuticals and Oncomed Pharmaceuticals, and his associates reported ties to numerous industry sources.

A biomarker for which a screening test is already available – lack of CDX2 expression – appears to identify the approximately 20% of stage II and 50% of stage III colon cancers that are at high risk of recurrence and would benefit from adjuvant chemotherapy, according to a report published online Jan. 21 in the New England Journal of Medicine.

Distinguishing the high-risk tumors from those unlikely to recur or progress would allow some patients to opt for adjuvant chemotherapy that has been shown to significantly raise the rates of overall and disease-free survival. At present, almost all patients with stage II colon cancer are treated using surgery alone, said Dr. Piero Dalerba of the Herbert Irving Comprehensive Cancer Center and the department of pathology and cell biology at Columbia University, New York, and his associates.

The investigators used a bioinformatics approach to search for biomarkers that would identify the most aggressive colon cancers: undifferentiated tumors characterized by immature, stem-like colonic epithelial cells and depleted of more mature cells. They focused on biomarkers for which clinical diagnostic tests are already available, to facilitate use in real-world clinical practice. Their search through 2,329 colon gene-expression array experiments found that when tumors do not express one particular protein, homeobox transcription factor CDX2, “a master regulator of intestinal development and oncogenesis” that is highly specifically expressed in intestinal epithelium, those tumors tend to have aggressive features such as advanced stage, vascular invasion, and BRAF mutation.

Survival outcomes were then compared in a discovery data set of 466 patients. The 5-year disease-free survival rate was significantly lower, at 41%, among the 32 patients who had CDX2-negative tumors than the 74% survival rate among the 434 patients with CDX2-positive tumors. The hazard ratio for disease recurrence among patients with CDX2-negative vs. CDX2-positive tumors was 2.73, Dr. Dalerba and his associates said (N Engl J Med. 2016 Jan 21. doi:10.1056/NEJMoa1506597).

The investigators confirmed these findings in a separate validation data set of 366 patients, of whom 48 had CDX2-negative and 318 had CDX2-positive tumors. Five-year disease-free survival (48% vs. 71%), overall survival (33% vs. 59%), and disease-specific survival (45% vs. 72%) were significantly lower with CDX2-negative tumors, and the HR for disease recurrence was 2.42.

To determine whether adjuvant chemotherapy would improve survival outcomes in patients with CDX2-negative tumors, the researchers assessed outcomes in an expanded dataset of 669 patients with stage II and 1,228 patients with stage III colon cancer. They confirmed that among patients with stage II CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (91%) than did those who didn’t receive adjuvant chemotherapy (56%). Similarly, among patients with stage III CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (74%) than those who did not receive adjuvant chemotherapy (37%).

This survival benefit was independent of many known risk factors, including tumor grade, they noted.

These results must be replicated in future prospective studies, because this study’s design was retrospective and exploratory, Dr. Dalerba and his associates added.

This work was supported by the National Comprehensive Cancer Network, the National Institutes of Health, Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, the California Institute for Regenerative Medicine, the U.S. Department of Defense, the Bladder Cancer Advocacy Network, and BD Biosciences. Dr. Dalerba reported ties to Quanticel Pharmaceuticals and Oncomed Pharmaceuticals, and his associates reported ties to numerous industry sources.

A biomarker for which a screening test is already available – lack of CDX2 expression – appears to identify the approximately 20% of stage II and 50% of stage III colon cancers that are at high risk of recurrence and would benefit from adjuvant chemotherapy, according to a report published online Jan. 21 in the New England Journal of Medicine.

Distinguishing the high-risk tumors from those unlikely to recur or progress would allow some patients to opt for adjuvant chemotherapy that has been shown to significantly raise the rates of overall and disease-free survival. At present, almost all patients with stage II colon cancer are treated using surgery alone, said Dr. Piero Dalerba of the Herbert Irving Comprehensive Cancer Center and the department of pathology and cell biology at Columbia University, New York, and his associates.

The investigators used a bioinformatics approach to search for biomarkers that would identify the most aggressive colon cancers: undifferentiated tumors characterized by immature, stem-like colonic epithelial cells and depleted of more mature cells. They focused on biomarkers for which clinical diagnostic tests are already available, to facilitate use in real-world clinical practice. Their search through 2,329 colon gene-expression array experiments found that when tumors do not express one particular protein, homeobox transcription factor CDX2, “a master regulator of intestinal development and oncogenesis” that is highly specifically expressed in intestinal epithelium, those tumors tend to have aggressive features such as advanced stage, vascular invasion, and BRAF mutation.

Survival outcomes were then compared in a discovery data set of 466 patients. The 5-year disease-free survival rate was significantly lower, at 41%, among the 32 patients who had CDX2-negative tumors than the 74% survival rate among the 434 patients with CDX2-positive tumors. The hazard ratio for disease recurrence among patients with CDX2-negative vs. CDX2-positive tumors was 2.73, Dr. Dalerba and his associates said (N Engl J Med. 2016 Jan 21. doi:10.1056/NEJMoa1506597).

The investigators confirmed these findings in a separate validation data set of 366 patients, of whom 48 had CDX2-negative and 318 had CDX2-positive tumors. Five-year disease-free survival (48% vs. 71%), overall survival (33% vs. 59%), and disease-specific survival (45% vs. 72%) were significantly lower with CDX2-negative tumors, and the HR for disease recurrence was 2.42.

To determine whether adjuvant chemotherapy would improve survival outcomes in patients with CDX2-negative tumors, the researchers assessed outcomes in an expanded dataset of 669 patients with stage II and 1,228 patients with stage III colon cancer. They confirmed that among patients with stage II CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (91%) than did those who didn’t receive adjuvant chemotherapy (56%). Similarly, among patients with stage III CDX2-negative tumors, those who received adjuvant chemotherapy had a higher rate of disease-free survival (74%) than those who did not receive adjuvant chemotherapy (37%).

This survival benefit was independent of many known risk factors, including tumor grade, they noted.

These results must be replicated in future prospective studies, because this study’s design was retrospective and exploratory, Dr. Dalerba and his associates added.

This work was supported by the National Comprehensive Cancer Network, the National Institutes of Health, Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, the California Institute for Regenerative Medicine, the U.S. Department of Defense, the Bladder Cancer Advocacy Network, and BD Biosciences. Dr. Dalerba reported ties to Quanticel Pharmaceuticals and Oncomed Pharmaceuticals, and his associates reported ties to numerous industry sources.

Current recommendations for identifying sacroiliitis on MRI to classify patients with nonradiographic axial spondyloarthritis should still depend on the presence of subchondral bone marrow edema, but additional evidence of structural lesions can be taken into account to define the presence of inflammatory lesions, according to a consensus review by experts from the Assessment in SpondyloArthritis International Society MRI working group.

The additional information provided by structural lesions, such as erosions, detected via MRI of the sacroiliac (SI) joint or spine is not necessary for the definition, but “may enhance confidence in the classification of axial SpA [spondyloarthritis],” said the panel of 16 rheumatologists, 4 radiologists, and 1 research fellow, who presented their summary and draft proposal at the January 2014 annual assembly of the Assessment in SpondyloArthritis International Society (ASAS), where members unanimously approved it (Ann Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208642).

© parisvas/Thinkstockphotos.com

The group’s goal was to examine whether new data published on axial SpA in the 5 years following the 2009 publication of the ASAS recommendations were “sufficient to merit a change in the MRI definition of a positive MRI and clarify any misunderstanding of the existing definition.”

Overall, the working group determined that the addition of “structural damage changes of the SI joints and the addition of features on MRI of the spine for classification purposes is not yet clear and this continues to be an important research agenda.”

Adding any single lesion or combination of lesions to the current classification criteria for nonradiographic axial spondyloarthritis (nr-axSpA) did not increase the sensitivity of the MRI definition without losing specificity in one cohort, whereas there was an unclear benefit to adding SI erosion to the definition in another cohort. The evaluation of these lesions on MRI depended on the use of T1 weighting and fat-suppression techniques, as well as the contextual interpretation of MRI, which currently add too much complexity to the definition of a positive SI joint MRI to be useful in achieving a “consensus for definitions for each MRI structural damage lesion and the setting of thresholds for any defined lesion or combination of lesions,” the working group wrote.

The panelists found that there was no consistent beneficial effect of adding features of SpA on spine MRI to the definition. Spine MRI added incremental sensitivity in other analyses, but also increased false-positive SpA diagnoses.

In a commentary reviewing the controversy and evidence for classifying diseases within the spectrum of axial SpA, Dr. Atul Deodhar of Oregon Health and Science University, Portland, and his colleagues noted that “there is no need to differentiate between a diagnosis of nr-axSpA and that of [ankylosing spondylitis] in clinical practice, since the only purpose for having these two labels is classification.” They said the need for formal distinction between nr-axSpA and ankylosing spondylitis may require some exceptions, such as when it is necessary “to specify an approved indication for TNFi [tumor necrosis factor inhibitor] therapy, when off-label use of biologics must be avoided ... and to clarify the presence of structural changes that are required for patients to receive coverage from their insurance carrier to use a TNFi” (Ann. Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208852).

The working panel and commentary authors declared having no competing interests.

[email protected]

Current recommendations for identifying sacroiliitis on MRI to classify patients with nonradiographic axial spondyloarthritis should still depend on the presence of subchondral bone marrow edema, but additional evidence of structural lesions can be taken into account to define the presence of inflammatory lesions, according to a consensus review by experts from the Assessment in SpondyloArthritis International Society MRI working group.

The additional information provided by structural lesions, such as erosions, detected via MRI of the sacroiliac (SI) joint or spine is not necessary for the definition, but “may enhance confidence in the classification of axial SpA [spondyloarthritis],” said the panel of 16 rheumatologists, 4 radiologists, and 1 research fellow, who presented their summary and draft proposal at the January 2014 annual assembly of the Assessment in SpondyloArthritis International Society (ASAS), where members unanimously approved it (Ann Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208642).

© parisvas/Thinkstockphotos.com

The group’s goal was to examine whether new data published on axial SpA in the 5 years following the 2009 publication of the ASAS recommendations were “sufficient to merit a change in the MRI definition of a positive MRI and clarify any misunderstanding of the existing definition.”

Overall, the working group determined that the addition of “structural damage changes of the SI joints and the addition of features on MRI of the spine for classification purposes is not yet clear and this continues to be an important research agenda.”

Adding any single lesion or combination of lesions to the current classification criteria for nonradiographic axial spondyloarthritis (nr-axSpA) did not increase the sensitivity of the MRI definition without losing specificity in one cohort, whereas there was an unclear benefit to adding SI erosion to the definition in another cohort. The evaluation of these lesions on MRI depended on the use of T1 weighting and fat-suppression techniques, as well as the contextual interpretation of MRI, which currently add too much complexity to the definition of a positive SI joint MRI to be useful in achieving a “consensus for definitions for each MRI structural damage lesion and the setting of thresholds for any defined lesion or combination of lesions,” the working group wrote.

The panelists found that there was no consistent beneficial effect of adding features of SpA on spine MRI to the definition. Spine MRI added incremental sensitivity in other analyses, but also increased false-positive SpA diagnoses.

In a commentary reviewing the controversy and evidence for classifying diseases within the spectrum of axial SpA, Dr. Atul Deodhar of Oregon Health and Science University, Portland, and his colleagues noted that “there is no need to differentiate between a diagnosis of nr-axSpA and that of [ankylosing spondylitis] in clinical practice, since the only purpose for having these two labels is classification.” They said the need for formal distinction between nr-axSpA and ankylosing spondylitis may require some exceptions, such as when it is necessary “to specify an approved indication for TNFi [tumor necrosis factor inhibitor] therapy, when off-label use of biologics must be avoided ... and to clarify the presence of structural changes that are required for patients to receive coverage from their insurance carrier to use a TNFi” (Ann. Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208852).

The working panel and commentary authors declared having no competing interests.

[email protected]

Current recommendations for identifying sacroiliitis on MRI to classify patients with nonradiographic axial spondyloarthritis should still depend on the presence of subchondral bone marrow edema, but additional evidence of structural lesions can be taken into account to define the presence of inflammatory lesions, according to a consensus review by experts from the Assessment in SpondyloArthritis International Society MRI working group.

The additional information provided by structural lesions, such as erosions, detected via MRI of the sacroiliac (SI) joint or spine is not necessary for the definition, but “may enhance confidence in the classification of axial SpA [spondyloarthritis],” said the panel of 16 rheumatologists, 4 radiologists, and 1 research fellow, who presented their summary and draft proposal at the January 2014 annual assembly of the Assessment in SpondyloArthritis International Society (ASAS), where members unanimously approved it (Ann Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208642).

© parisvas/Thinkstockphotos.com

The group’s goal was to examine whether new data published on axial SpA in the 5 years following the 2009 publication of the ASAS recommendations were “sufficient to merit a change in the MRI definition of a positive MRI and clarify any misunderstanding of the existing definition.”

Overall, the working group determined that the addition of “structural damage changes of the SI joints and the addition of features on MRI of the spine for classification purposes is not yet clear and this continues to be an important research agenda.”

Adding any single lesion or combination of lesions to the current classification criteria for nonradiographic axial spondyloarthritis (nr-axSpA) did not increase the sensitivity of the MRI definition without losing specificity in one cohort, whereas there was an unclear benefit to adding SI erosion to the definition in another cohort. The evaluation of these lesions on MRI depended on the use of T1 weighting and fat-suppression techniques, as well as the contextual interpretation of MRI, which currently add too much complexity to the definition of a positive SI joint MRI to be useful in achieving a “consensus for definitions for each MRI structural damage lesion and the setting of thresholds for any defined lesion or combination of lesions,” the working group wrote.

The panelists found that there was no consistent beneficial effect of adding features of SpA on spine MRI to the definition. Spine MRI added incremental sensitivity in other analyses, but also increased false-positive SpA diagnoses.

In a commentary reviewing the controversy and evidence for classifying diseases within the spectrum of axial SpA, Dr. Atul Deodhar of Oregon Health and Science University, Portland, and his colleagues noted that “there is no need to differentiate between a diagnosis of nr-axSpA and that of [ankylosing spondylitis] in clinical practice, since the only purpose for having these two labels is classification.” They said the need for formal distinction between nr-axSpA and ankylosing spondylitis may require some exceptions, such as when it is necessary “to specify an approved indication for TNFi [tumor necrosis factor inhibitor] therapy, when off-label use of biologics must be avoided ... and to clarify the presence of structural changes that are required for patients to receive coverage from their insurance carrier to use a TNFi” (Ann. Rheum Dis. 2016 Jan 14. doi: 10.1136/annrheumdis-2015-208852).

The working panel and commentary authors declared having no competing interests.

[email protected]

SNOWMASS, COLO. – It’s time to eliminate the practice of prescribing aspirin for stroke prevention in patients with atrial fibrillation and a CHA₂DS₂-VASc score of 1, two eminent cardiologists agreed at the Annual Cardiovascular Conference at Snowmass.

“The European guidelines have done away with aspirin for stroke prevention in atrial fibrillation. It barely made it into our current U.S. guidelines. I don’t think aspirin should be in there and I don’t think it will be there in the next guidelines. The role of aspirin will fall away,” predicted Dr. Bernard J. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

“It’s not that aspirin is less effective than the oral anticoagulants, it’s that there’s no role for it. There are no good data to support aspirin in the prevention of stroke in atrial fibrillation,” he declared.

Dr. N.A. Mark Estes III agreed the aspirin evidence is seriously flawed.

“The use of aspirin has probably been misguided, based upon a single trial which showed a profound effect and was probably just an anomaly,” according to Dr. Estes, a past president of the Heart Rhythm Society who is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University, Boston.

The sole positive clinical trial of aspirin versus placebo, the 25-year-old Stroke Prevention in Atrial Fibrillation (SPAF) study (Circulation. 1991 Aug;84[2]:527-39), found an unrealistically high stroke protection benefit for aspirin, a result made implausible by multiple other randomized trials showing no benefit, the cardiologists agreed.

“In our current guidelines for atrial fibrillation (Circulation. 2014 Dec 2;130[23]:2071-104), aspirin can be considered as a Class IIb level of evidence C recommendation in patients with a CHA₂DS₂-VASc of 1. But I would just take it off of your clinical armamentarium because the best available data indicates that it doesn’t prevent strokes. I’m certainly not using it in my patients. Increasingly in my patients with a CHA₂DS₂-VASc of 1, I’m discussing the risks and benefits of a NOAC [novel oral anticoagulant],” Dr. Estes said.

Dr. Gersh was also critical of another common practice in stroke prevention in atrial fibrillation: concomitant use of aspirin with an oral anticoagulant.

“We use too much aspirin in patients on oral anticoagulation. Aspirin is perhaps the major cause of bleeding in patients on an oral anticoagulant. Other than in people with a drug-eluting stent, there’s no role at all for aspirin in stroke prevention,” he asserted.

He was coauthor of an analysis of 7,347 participants in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) who were on an oral anticoagulant. Fully 35% of them were also on aspirin. In a multivariate analysis, concomitant aspirin and oral anticoagulation was independently associated with a 53% increased risk of major bleeding and a 52% increase in hospitalization for bleeding, compared with atrial fibrillation patients on an oral anticoagulant alone (Circulation. 2013 Aug 13;128[7]:721-8).

Moreover, the widespread use of dual therapy in this real-world registry didn’t appear to be rational. Thirty-nine percent of those on aspirin plus an oral anticoagulant had no history of atherosclerotic disease, the presence of which would be an indication for considering aspirin. And 17% of dual therapy patients had an elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk score of 5 or more, making dual therapy particularly risky.

This clinically important interaction between aspirin and oral anticoagulation was recently underscored in an analysis of rivaroxaban-treated patients in the ROCKET AF trial, Dr. Gersh observed. Long-term use of aspirin at entry into this pivotal randomized trial of rivaroxaban (Xarelto) versus warfarin in patients with atrial fibrillation proved to be an independent predictor of a 47% increase in the risk of gastrointestinal bleeding, compared with patients on rivaroxaban alone (J Am Coll Cardiol. 2015 Dec 1;66[21]:2271-81).

He added that there is no evidence that combining aspirin and oral anticoagulation enhances stroke prevention beyond the marked benefit achieved with oral anticoagulation alone.

Dr. Gersh reported serving on the leadership of the ORBIT-AF Registry, which was sponsored by Janssen Pharmaceuticals. Dr. Estes reported having no financial conflicts relevant to this discussion.

[email protected]

SNOWMASS, COLO. – It’s time to eliminate the practice of prescribing aspirin for stroke prevention in patients with atrial fibrillation and a CHA₂DS₂-VASc score of 1, two eminent cardiologists agreed at the Annual Cardiovascular Conference at Snowmass.

“The European guidelines have done away with aspirin for stroke prevention in atrial fibrillation. It barely made it into our current U.S. guidelines. I don’t think aspirin should be in there and I don’t think it will be there in the next guidelines. The role of aspirin will fall away,” predicted Dr. Bernard J. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

“It’s not that aspirin is less effective than the oral anticoagulants, it’s that there’s no role for it. There are no good data to support aspirin in the prevention of stroke in atrial fibrillation,” he declared.

Dr. N.A. Mark Estes III agreed the aspirin evidence is seriously flawed.

“The use of aspirin has probably been misguided, based upon a single trial which showed a profound effect and was probably just an anomaly,” according to Dr. Estes, a past president of the Heart Rhythm Society who is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University, Boston.

The sole positive clinical trial of aspirin versus placebo, the 25-year-old Stroke Prevention in Atrial Fibrillation (SPAF) study (Circulation. 1991 Aug;84[2]:527-39), found an unrealistically high stroke protection benefit for aspirin, a result made implausible by multiple other randomized trials showing no benefit, the cardiologists agreed.

“In our current guidelines for atrial fibrillation (Circulation. 2014 Dec 2;130[23]:2071-104), aspirin can be considered as a Class IIb level of evidence C recommendation in patients with a CHA₂DS₂-VASc of 1. But I would just take it off of your clinical armamentarium because the best available data indicates that it doesn’t prevent strokes. I’m certainly not using it in my patients. Increasingly in my patients with a CHA₂DS₂-VASc of 1, I’m discussing the risks and benefits of a NOAC [novel oral anticoagulant],” Dr. Estes said.

Dr. Gersh was also critical of another common practice in stroke prevention in atrial fibrillation: concomitant use of aspirin with an oral anticoagulant.

“We use too much aspirin in patients on oral anticoagulation. Aspirin is perhaps the major cause of bleeding in patients on an oral anticoagulant. Other than in people with a drug-eluting stent, there’s no role at all for aspirin in stroke prevention,” he asserted.

He was coauthor of an analysis of 7,347 participants in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) who were on an oral anticoagulant. Fully 35% of them were also on aspirin. In a multivariate analysis, concomitant aspirin and oral anticoagulation was independently associated with a 53% increased risk of major bleeding and a 52% increase in hospitalization for bleeding, compared with atrial fibrillation patients on an oral anticoagulant alone (Circulation. 2013 Aug 13;128[7]:721-8).

Moreover, the widespread use of dual therapy in this real-world registry didn’t appear to be rational. Thirty-nine percent of those on aspirin plus an oral anticoagulant had no history of atherosclerotic disease, the presence of which would be an indication for considering aspirin. And 17% of dual therapy patients had an elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk score of 5 or more, making dual therapy particularly risky.

This clinically important interaction between aspirin and oral anticoagulation was recently underscored in an analysis of rivaroxaban-treated patients in the ROCKET AF trial, Dr. Gersh observed. Long-term use of aspirin at entry into this pivotal randomized trial of rivaroxaban (Xarelto) versus warfarin in patients with atrial fibrillation proved to be an independent predictor of a 47% increase in the risk of gastrointestinal bleeding, compared with patients on rivaroxaban alone (J Am Coll Cardiol. 2015 Dec 1;66[21]:2271-81).

He added that there is no evidence that combining aspirin and oral anticoagulation enhances stroke prevention beyond the marked benefit achieved with oral anticoagulation alone.

Dr. Gersh reported serving on the leadership of the ORBIT-AF Registry, which was sponsored by Janssen Pharmaceuticals. Dr. Estes reported having no financial conflicts relevant to this discussion.

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SNOWMASS, COLO. – It’s time to eliminate the practice of prescribing aspirin for stroke prevention in patients with atrial fibrillation and a CHA₂DS₂-VASc score of 1, two eminent cardiologists agreed at the Annual Cardiovascular Conference at Snowmass.

“The European guidelines have done away with aspirin for stroke prevention in atrial fibrillation. It barely made it into our current U.S. guidelines. I don’t think aspirin should be in there and I don’t think it will be there in the next guidelines. The role of aspirin will fall away,” predicted Dr. Bernard J. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

“It’s not that aspirin is less effective than the oral anticoagulants, it’s that there’s no role for it. There are no good data to support aspirin in the prevention of stroke in atrial fibrillation,” he declared.

Dr. N.A. Mark Estes III agreed the aspirin evidence is seriously flawed.

“The use of aspirin has probably been misguided, based upon a single trial which showed a profound effect and was probably just an anomaly,” according to Dr. Estes, a past president of the Heart Rhythm Society who is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University, Boston.

The sole positive clinical trial of aspirin versus placebo, the 25-year-old Stroke Prevention in Atrial Fibrillation (SPAF) study (Circulation. 1991 Aug;84[2]:527-39), found an unrealistically high stroke protection benefit for aspirin, a result made implausible by multiple other randomized trials showing no benefit, the cardiologists agreed.

“In our current guidelines for atrial fibrillation (Circulation. 2014 Dec 2;130[23]:2071-104), aspirin can be considered as a Class IIb level of evidence C recommendation in patients with a CHA₂DS₂-VASc of 1. But I would just take it off of your clinical armamentarium because the best available data indicates that it doesn’t prevent strokes. I’m certainly not using it in my patients. Increasingly in my patients with a CHA₂DS₂-VASc of 1, I’m discussing the risks and benefits of a NOAC [novel oral anticoagulant],” Dr. Estes said.

Dr. Gersh was also critical of another common practice in stroke prevention in atrial fibrillation: concomitant use of aspirin with an oral anticoagulant.

“We use too much aspirin in patients on oral anticoagulation. Aspirin is perhaps the major cause of bleeding in patients on an oral anticoagulant. Other than in people with a drug-eluting stent, there’s no role at all for aspirin in stroke prevention,” he asserted.

He was coauthor of an analysis of 7,347 participants in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) who were on an oral anticoagulant. Fully 35% of them were also on aspirin. In a multivariate analysis, concomitant aspirin and oral anticoagulation was independently associated with a 53% increased risk of major bleeding and a 52% increase in hospitalization for bleeding, compared with atrial fibrillation patients on an oral anticoagulant alone (Circulation. 2013 Aug 13;128[7]:721-8).

Moreover, the widespread use of dual therapy in this real-world registry didn’t appear to be rational. Thirty-nine percent of those on aspirin plus an oral anticoagulant had no history of atherosclerotic disease, the presence of which would be an indication for considering aspirin. And 17% of dual therapy patients had an elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk score of 5 or more, making dual therapy particularly risky.

This clinically important interaction between aspirin and oral anticoagulation was recently underscored in an analysis of rivaroxaban-treated patients in the ROCKET AF trial, Dr. Gersh observed. Long-term use of aspirin at entry into this pivotal randomized trial of rivaroxaban (Xarelto) versus warfarin in patients with atrial fibrillation proved to be an independent predictor of a 47% increase in the risk of gastrointestinal bleeding, compared with patients on rivaroxaban alone (J Am Coll Cardiol. 2015 Dec 1;66[21]:2271-81).

He added that there is no evidence that combining aspirin and oral anticoagulation enhances stroke prevention beyond the marked benefit achieved with oral anticoagulation alone.

Dr. Gersh reported serving on the leadership of the ORBIT-AF Registry, which was sponsored by Janssen Pharmaceuticals. Dr. Estes reported having no financial conflicts relevant to this discussion.

[email protected]