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The rate of death from treatment-related late effects such as subsequent cancers and cardiopulmonary conditions has decreased among childhood cancer survivors, according to researchers.

At 15 years post diagnosis, the cumulative incidence of death from any cause for survivors diagnosed in the 1970s was 10.7%, 7.9% for those diagnosed in the 1980s, and 5.8% for those diagnosed in the 1990s (P less than .001). The cumulative incidence of death due to health-related causes, which include late effects of cancer therapy, were 3.1%, 2.4%, and 1.9%, respectively (P less than .001).

Purestock/thinkstockphotos.com

Results indicate that “the strategy of reducing treatment exposures in order to decrease the frequency of late effects is translating into a significant reduction in observed late mortality and an extension of the life span of children and adolescents who are successfully treated for cancer,” wrote Dr. Gregory Armstrong of St. Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (N Engl J Med. 2016 Jan 13. doi: 10.1056/NEJMoa1510795).

A multivariate model showed that more recent treatment eras were associated with a reduced rate of death. The adjusted relative rate per every 5 years for death due to subsequent neoplasms was 0.83 (95% CI, 0.78-0.88), for cardiac causes, 0.77 (0.68-0.86), and for pulmonary causes, 0.77 (0.66-0.89).

Reductions across treatment eras in the rate of death from health-related causes were observed among survivors of acute lymphoblastic leukemia (3.2% in the early 1970s to 2.1% in the 1990s, P less than .001), Hodgkin lymphoma (5.3% to 2.6%, P = .006), Wilms tumor (2.6% to 0.4%, P = .005), and astrocytoma (4.7% to 1.8%, P = .02).

Temporal reductions in exposure to radiotherapy and anthracyclines occurred in treatment for acute lymphoblastic leukemia, Hodgkin lymphoma, Wilms tumor, and astrocytoma. Health-related mortality reductions were observed concurrently with reduced therapeutic exposures for acute lymphoblastic leukemia and Wilms tumor. For Hodgkin lymphoma and astrocytoma, other factors such as improved screening for late effects of cancer treatment appear to account for reductions in late health-related mortality.

For certain cancers, primarily neuroblastoma, late mortality has increased in recent decades. Increased therapeutic intensity has improved 5-year survival but increased the risk of late effects.

The reduced rate of death from recurrence or progression of primary cancers is the main driver to reductions in all-cause mortality, consistent with results from previous studies.

The retrospective Childhood Cancer Survivor Study evaluated 34,033 patients diagnosed at 31 hospitals in the United States and Canada from 1970 through 1999. In total, 3,958 deaths occurred, 2,002 due to primary cancer and 1,618 due to health-related causes: 746 subsequent neoplasms, 241 cardiac causes, 137 pulmonary causes, and 494 from other causes.

The rate of death from treatment-related late effects such as subsequent cancers and cardiopulmonary conditions has decreased among childhood cancer survivors, according to researchers.

At 15 years post diagnosis, the cumulative incidence of death from any cause for survivors diagnosed in the 1970s was 10.7%, 7.9% for those diagnosed in the 1980s, and 5.8% for those diagnosed in the 1990s (P less than .001). The cumulative incidence of death due to health-related causes, which include late effects of cancer therapy, were 3.1%, 2.4%, and 1.9%, respectively (P less than .001).

Purestock/thinkstockphotos.com

Results indicate that “the strategy of reducing treatment exposures in order to decrease the frequency of late effects is translating into a significant reduction in observed late mortality and an extension of the life span of children and adolescents who are successfully treated for cancer,” wrote Dr. Gregory Armstrong of St. Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (N Engl J Med. 2016 Jan 13. doi: 10.1056/NEJMoa1510795).

A multivariate model showed that more recent treatment eras were associated with a reduced rate of death. The adjusted relative rate per every 5 years for death due to subsequent neoplasms was 0.83 (95% CI, 0.78-0.88), for cardiac causes, 0.77 (0.68-0.86), and for pulmonary causes, 0.77 (0.66-0.89).

Reductions across treatment eras in the rate of death from health-related causes were observed among survivors of acute lymphoblastic leukemia (3.2% in the early 1970s to 2.1% in the 1990s, P less than .001), Hodgkin lymphoma (5.3% to 2.6%, P = .006), Wilms tumor (2.6% to 0.4%, P = .005), and astrocytoma (4.7% to 1.8%, P = .02).

Temporal reductions in exposure to radiotherapy and anthracyclines occurred in treatment for acute lymphoblastic leukemia, Hodgkin lymphoma, Wilms tumor, and astrocytoma. Health-related mortality reductions were observed concurrently with reduced therapeutic exposures for acute lymphoblastic leukemia and Wilms tumor. For Hodgkin lymphoma and astrocytoma, other factors such as improved screening for late effects of cancer treatment appear to account for reductions in late health-related mortality.

For certain cancers, primarily neuroblastoma, late mortality has increased in recent decades. Increased therapeutic intensity has improved 5-year survival but increased the risk of late effects.

The reduced rate of death from recurrence or progression of primary cancers is the main driver to reductions in all-cause mortality, consistent with results from previous studies.

The retrospective Childhood Cancer Survivor Study evaluated 34,033 patients diagnosed at 31 hospitals in the United States and Canada from 1970 through 1999. In total, 3,958 deaths occurred, 2,002 due to primary cancer and 1,618 due to health-related causes: 746 subsequent neoplasms, 241 cardiac causes, 137 pulmonary causes, and 494 from other causes.

The rate of death from treatment-related late effects such as subsequent cancers and cardiopulmonary conditions has decreased among childhood cancer survivors, according to researchers.

At 15 years post diagnosis, the cumulative incidence of death from any cause for survivors diagnosed in the 1970s was 10.7%, 7.9% for those diagnosed in the 1980s, and 5.8% for those diagnosed in the 1990s (P less than .001). The cumulative incidence of death due to health-related causes, which include late effects of cancer therapy, were 3.1%, 2.4%, and 1.9%, respectively (P less than .001).

Purestock/thinkstockphotos.com

Results indicate that “the strategy of reducing treatment exposures in order to decrease the frequency of late effects is translating into a significant reduction in observed late mortality and an extension of the life span of children and adolescents who are successfully treated for cancer,” wrote Dr. Gregory Armstrong of St. Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (N Engl J Med. 2016 Jan 13. doi: 10.1056/NEJMoa1510795).

A multivariate model showed that more recent treatment eras were associated with a reduced rate of death. The adjusted relative rate per every 5 years for death due to subsequent neoplasms was 0.83 (95% CI, 0.78-0.88), for cardiac causes, 0.77 (0.68-0.86), and for pulmonary causes, 0.77 (0.66-0.89).

Reductions across treatment eras in the rate of death from health-related causes were observed among survivors of acute lymphoblastic leukemia (3.2% in the early 1970s to 2.1% in the 1990s, P less than .001), Hodgkin lymphoma (5.3% to 2.6%, P = .006), Wilms tumor (2.6% to 0.4%, P = .005), and astrocytoma (4.7% to 1.8%, P = .02).

Temporal reductions in exposure to radiotherapy and anthracyclines occurred in treatment for acute lymphoblastic leukemia, Hodgkin lymphoma, Wilms tumor, and astrocytoma. Health-related mortality reductions were observed concurrently with reduced therapeutic exposures for acute lymphoblastic leukemia and Wilms tumor. For Hodgkin lymphoma and astrocytoma, other factors such as improved screening for late effects of cancer treatment appear to account for reductions in late health-related mortality.

For certain cancers, primarily neuroblastoma, late mortality has increased in recent decades. Increased therapeutic intensity has improved 5-year survival but increased the risk of late effects.

The reduced rate of death from recurrence or progression of primary cancers is the main driver to reductions in all-cause mortality, consistent with results from previous studies.

The retrospective Childhood Cancer Survivor Study evaluated 34,033 patients diagnosed at 31 hospitals in the United States and Canada from 1970 through 1999. In total, 3,958 deaths occurred, 2,002 due to primary cancer and 1,618 due to health-related causes: 746 subsequent neoplasms, 241 cardiac causes, 137 pulmonary causes, and 494 from other causes.

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

Women aged 50-74 years should undergo biennial screening mammography, and the decision to screen before age 50 should be individualized, according to a final recommendation from the U.S. Preventive Services Task Force.

© Bill Branson/National Cancer Institute

The recommendation statement, published Jan. 11 in Annals of Internal Medicine, is based on a comprehensive review of data since 2009, when the USPSTF last released breast cancer screening recommendations, and follows a public comment period in early 2015.

“The task force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. Mammography can also be effective for women in their 40s, but the benefits are less and the harms potentially greater. The decision by women to start screening in their 40s should be an individual one, made in partnership with a doctor,” according to a statement from the USPSTF.

The new recommendations will not affect private insurance coverage of mammography without cost sharing as outlined in the Affordable Care Act. As part of a spending bill enacted in December 2015, Congress passed a provision placing a 2-year moratorium on the use of any new USPSTF recommendations related to breast cancer screening to determine coverage, effectively preserving mammography coverage without cost sharing for women aged 40 years and older.

Recommendations by age

The latest USPSTF recommendations by age state that women aged 40-49 years should base their screening decision on personal values, preferences, and health history; women with a family history of breast cancer may benefit more than average-risk women by beginning screening before age 50. This is a C recommendation, indicating “moderate certainty that net benefit is small.”

The recommendation for biennial screening of those aged 50-74 is a B recommendation indicating “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial,” Dr. Albert L. Siu, task force chair, reported on behalf of the USPSTF (Ann Intern Med. 2016;164:279-96. doi: 10.7326/M15-2886).

The task force found inadequate evidence to recommend for or against screening those aged 75 and older.

Final evidence documents, including a systematic review of data on the harms associated with breast cancer screening and a modeling study of the benefits and harms associated with different screening strategies, are published along with the recommendation statement.

The USPSTF did not make a recommendations about the use of digital breast tomosynthesis as a primary screening method for breast cancer, noting that the current evidence is insufficient. Evidence also was insufficient to make a recommendation on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging, digital breast tomosynthesis, or other methods in women with dense breasts who had a negative screening mammogram.

Dousing the ‘firestorm’

In an editorial penned by Annals of Internal Medicine Editor-in-Chief and Senior Vice President of the American College of Physicians Christine Laine and her colleagues, they urged a dousing of the “firestorm around breast cancer screening.”

That firestorm was ignited with the 2009 USPSTF breast cancer screening recommendation and was rekindled when the current recommendation was presented in draft form in 2015.

However, “the USPSTF did a difficult job well” and based its recommendations on an important understanding of the updated evidence, as well as potential harms and tradeoffs of different screening strategies, the authors wrote.

“When the USPSTF posted its draft recommendations for comment, it noted, ‘Women deserve to be aware of what the science says so they can make the best choice for themselves, together with their doctor.’ We could not agree more. Let’s douse the flames and clear the smoke so that we can clearly see what the evidence shows and where we need to focus efforts to fill gaps in our knowledge so that women, along with their health care providers, can make the best decision to reduce their risk for breast cancer–related morbidity and mortality,” they wrote (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-2978).

ACOG supports screening at 40

The American College of Obstetricians and Gynecologists is standing by its recommendation of annual mammograms beginning at age 40 and continues to support use of clinical breast examinations. In a Jan. 11 statement, Dr. Mark S. DeFrancesco, ACOG president, said that “evidence and experience have shown that early detection can lead to improved outcomes in women diagnosed with breast cancer.”

The organization similarly stood by its recommendation in October 2015, when the American Cancer Society released recommendations for annual screening mammography for asymptomatic women at average risk for breast cancer beginning at age 45 years, with a transition to biennial screening mammography beginning at age 55 (JAMA. 2015;314[15]:1599-1614. doi: 10.1001/jama.2015.12783).

ACOG also supports the omnibus legislation passed by Congress in December that provides 2 years of no-copay coverage of breast cancer screening after age 40 via a moratorium on new breast cancer screening recommendations to allow time for additional research, an ACOG spokesperson said in an interview.

“ACOG strongly supports shared decision-making between doctor and patient, and in the case of screening for breast cancer, it is essential,” Dr. DeFrancesco said. “Given the differences among current organizational recommendations on breast cancer screening, we recognize that there may be confusion among women about when they should begin screening for breast cancer. ACOG encourages women to discuss this with their doctor, including concerns such as family history of cancer, risk factors such as overweight, and their own personal experiences with breast cancer. Moreover, it is essential that physicians counsel women about the potential consequences of mammography, including false positives.”

ACOG will convene a consensus conference later in January “with the intent to develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide” in an effort to “avoid the confusion that currently exists among the women we treat,” according to the statement.

The issue of divergence – and convergence – among various guidelines was the topic of another editorial published in conjunction with the USPSTF recommendations. In that article, task force chair Dr. Siu and his colleagues acknowledged that disagreements exist but stressed that “it would be a disservice to women and their clinicians if these disagreements obscured a strong emerging convergence among groups who have recently issued evidence-based guidelines” (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-3065).

The operations of the USPSTF are supported by the Agency for Healthcare Research and Quality. One of the members of the USPSTF reported receiving past grants and contracts from the National Cancer Institute and the Centers for Disease Control and Prevention.

[email protected]

Women aged 50-74 years should undergo biennial screening mammography, and the decision to screen before age 50 should be individualized, according to a final recommendation from the U.S. Preventive Services Task Force.

© Bill Branson/National Cancer Institute

The recommendation statement, published Jan. 11 in Annals of Internal Medicine, is based on a comprehensive review of data since 2009, when the USPSTF last released breast cancer screening recommendations, and follows a public comment period in early 2015.

“The task force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. Mammography can also be effective for women in their 40s, but the benefits are less and the harms potentially greater. The decision by women to start screening in their 40s should be an individual one, made in partnership with a doctor,” according to a statement from the USPSTF.

The new recommendations will not affect private insurance coverage of mammography without cost sharing as outlined in the Affordable Care Act. As part of a spending bill enacted in December 2015, Congress passed a provision placing a 2-year moratorium on the use of any new USPSTF recommendations related to breast cancer screening to determine coverage, effectively preserving mammography coverage without cost sharing for women aged 40 years and older.

Recommendations by age

The latest USPSTF recommendations by age state that women aged 40-49 years should base their screening decision on personal values, preferences, and health history; women with a family history of breast cancer may benefit more than average-risk women by beginning screening before age 50. This is a C recommendation, indicating “moderate certainty that net benefit is small.”

The recommendation for biennial screening of those aged 50-74 is a B recommendation indicating “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial,” Dr. Albert L. Siu, task force chair, reported on behalf of the USPSTF (Ann Intern Med. 2016;164:279-96. doi: 10.7326/M15-2886).

The task force found inadequate evidence to recommend for or against screening those aged 75 and older.

Final evidence documents, including a systematic review of data on the harms associated with breast cancer screening and a modeling study of the benefits and harms associated with different screening strategies, are published along with the recommendation statement.

The USPSTF did not make a recommendations about the use of digital breast tomosynthesis as a primary screening method for breast cancer, noting that the current evidence is insufficient. Evidence also was insufficient to make a recommendation on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging, digital breast tomosynthesis, or other methods in women with dense breasts who had a negative screening mammogram.

Dousing the ‘firestorm’

In an editorial penned by Annals of Internal Medicine Editor-in-Chief and Senior Vice President of the American College of Physicians Christine Laine and her colleagues, they urged a dousing of the “firestorm around breast cancer screening.”

That firestorm was ignited with the 2009 USPSTF breast cancer screening recommendation and was rekindled when the current recommendation was presented in draft form in 2015.

However, “the USPSTF did a difficult job well” and based its recommendations on an important understanding of the updated evidence, as well as potential harms and tradeoffs of different screening strategies, the authors wrote.

“When the USPSTF posted its draft recommendations for comment, it noted, ‘Women deserve to be aware of what the science says so they can make the best choice for themselves, together with their doctor.’ We could not agree more. Let’s douse the flames and clear the smoke so that we can clearly see what the evidence shows and where we need to focus efforts to fill gaps in our knowledge so that women, along with their health care providers, can make the best decision to reduce their risk for breast cancer–related morbidity and mortality,” they wrote (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-2978).

ACOG supports screening at 40

The American College of Obstetricians and Gynecologists is standing by its recommendation of annual mammograms beginning at age 40 and continues to support use of clinical breast examinations. In a Jan. 11 statement, Dr. Mark S. DeFrancesco, ACOG president, said that “evidence and experience have shown that early detection can lead to improved outcomes in women diagnosed with breast cancer.”

The organization similarly stood by its recommendation in October 2015, when the American Cancer Society released recommendations for annual screening mammography for asymptomatic women at average risk for breast cancer beginning at age 45 years, with a transition to biennial screening mammography beginning at age 55 (JAMA. 2015;314[15]:1599-1614. doi: 10.1001/jama.2015.12783).

ACOG also supports the omnibus legislation passed by Congress in December that provides 2 years of no-copay coverage of breast cancer screening after age 40 via a moratorium on new breast cancer screening recommendations to allow time for additional research, an ACOG spokesperson said in an interview.

“ACOG strongly supports shared decision-making between doctor and patient, and in the case of screening for breast cancer, it is essential,” Dr. DeFrancesco said. “Given the differences among current organizational recommendations on breast cancer screening, we recognize that there may be confusion among women about when they should begin screening for breast cancer. ACOG encourages women to discuss this with their doctor, including concerns such as family history of cancer, risk factors such as overweight, and their own personal experiences with breast cancer. Moreover, it is essential that physicians counsel women about the potential consequences of mammography, including false positives.”

ACOG will convene a consensus conference later in January “with the intent to develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide” in an effort to “avoid the confusion that currently exists among the women we treat,” according to the statement.

The issue of divergence – and convergence – among various guidelines was the topic of another editorial published in conjunction with the USPSTF recommendations. In that article, task force chair Dr. Siu and his colleagues acknowledged that disagreements exist but stressed that “it would be a disservice to women and their clinicians if these disagreements obscured a strong emerging convergence among groups who have recently issued evidence-based guidelines” (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-3065).

The operations of the USPSTF are supported by the Agency for Healthcare Research and Quality. One of the members of the USPSTF reported receiving past grants and contracts from the National Cancer Institute and the Centers for Disease Control and Prevention.

[email protected]

Women aged 50-74 years should undergo biennial screening mammography, and the decision to screen before age 50 should be individualized, according to a final recommendation from the U.S. Preventive Services Task Force.

© Bill Branson/National Cancer Institute

The recommendation statement, published Jan. 11 in Annals of Internal Medicine, is based on a comprehensive review of data since 2009, when the USPSTF last released breast cancer screening recommendations, and follows a public comment period in early 2015.

“The task force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. Mammography can also be effective for women in their 40s, but the benefits are less and the harms potentially greater. The decision by women to start screening in their 40s should be an individual one, made in partnership with a doctor,” according to a statement from the USPSTF.

The new recommendations will not affect private insurance coverage of mammography without cost sharing as outlined in the Affordable Care Act. As part of a spending bill enacted in December 2015, Congress passed a provision placing a 2-year moratorium on the use of any new USPSTF recommendations related to breast cancer screening to determine coverage, effectively preserving mammography coverage without cost sharing for women aged 40 years and older.

Recommendations by age

The latest USPSTF recommendations by age state that women aged 40-49 years should base their screening decision on personal values, preferences, and health history; women with a family history of breast cancer may benefit more than average-risk women by beginning screening before age 50. This is a C recommendation, indicating “moderate certainty that net benefit is small.”

The recommendation for biennial screening of those aged 50-74 is a B recommendation indicating “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial,” Dr. Albert L. Siu, task force chair, reported on behalf of the USPSTF (Ann Intern Med. 2016;164:279-96. doi: 10.7326/M15-2886).

The task force found inadequate evidence to recommend for or against screening those aged 75 and older.

Final evidence documents, including a systematic review of data on the harms associated with breast cancer screening and a modeling study of the benefits and harms associated with different screening strategies, are published along with the recommendation statement.

The USPSTF did not make a recommendations about the use of digital breast tomosynthesis as a primary screening method for breast cancer, noting that the current evidence is insufficient. Evidence also was insufficient to make a recommendation on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging, digital breast tomosynthesis, or other methods in women with dense breasts who had a negative screening mammogram.

Dousing the ‘firestorm’

In an editorial penned by Annals of Internal Medicine Editor-in-Chief and Senior Vice President of the American College of Physicians Christine Laine and her colleagues, they urged a dousing of the “firestorm around breast cancer screening.”

That firestorm was ignited with the 2009 USPSTF breast cancer screening recommendation and was rekindled when the current recommendation was presented in draft form in 2015.

However, “the USPSTF did a difficult job well” and based its recommendations on an important understanding of the updated evidence, as well as potential harms and tradeoffs of different screening strategies, the authors wrote.

“When the USPSTF posted its draft recommendations for comment, it noted, ‘Women deserve to be aware of what the science says so they can make the best choice for themselves, together with their doctor.’ We could not agree more. Let’s douse the flames and clear the smoke so that we can clearly see what the evidence shows and where we need to focus efforts to fill gaps in our knowledge so that women, along with their health care providers, can make the best decision to reduce their risk for breast cancer–related morbidity and mortality,” they wrote (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-2978).

ACOG supports screening at 40

The American College of Obstetricians and Gynecologists is standing by its recommendation of annual mammograms beginning at age 40 and continues to support use of clinical breast examinations. In a Jan. 11 statement, Dr. Mark S. DeFrancesco, ACOG president, said that “evidence and experience have shown that early detection can lead to improved outcomes in women diagnosed with breast cancer.”

The organization similarly stood by its recommendation in October 2015, when the American Cancer Society released recommendations for annual screening mammography for asymptomatic women at average risk for breast cancer beginning at age 45 years, with a transition to biennial screening mammography beginning at age 55 (JAMA. 2015;314[15]:1599-1614. doi: 10.1001/jama.2015.12783).

ACOG also supports the omnibus legislation passed by Congress in December that provides 2 years of no-copay coverage of breast cancer screening after age 40 via a moratorium on new breast cancer screening recommendations to allow time for additional research, an ACOG spokesperson said in an interview.

“ACOG strongly supports shared decision-making between doctor and patient, and in the case of screening for breast cancer, it is essential,” Dr. DeFrancesco said. “Given the differences among current organizational recommendations on breast cancer screening, we recognize that there may be confusion among women about when they should begin screening for breast cancer. ACOG encourages women to discuss this with their doctor, including concerns such as family history of cancer, risk factors such as overweight, and their own personal experiences with breast cancer. Moreover, it is essential that physicians counsel women about the potential consequences of mammography, including false positives.”

ACOG will convene a consensus conference later in January “with the intent to develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide” in an effort to “avoid the confusion that currently exists among the women we treat,” according to the statement.

The issue of divergence – and convergence – among various guidelines was the topic of another editorial published in conjunction with the USPSTF recommendations. In that article, task force chair Dr. Siu and his colleagues acknowledged that disagreements exist but stressed that “it would be a disservice to women and their clinicians if these disagreements obscured a strong emerging convergence among groups who have recently issued evidence-based guidelines” (Ann Intern Med. 2016 Jan 11. doi:10.7326/M15-3065).

The operations of the USPSTF are supported by the Agency for Healthcare Research and Quality. One of the members of the USPSTF reported receiving past grants and contracts from the National Cancer Institute and the Centers for Disease Control and Prevention.

[email protected]

If you can’t find anything that interests you at HM16, check your caffeine level. You might need a cup.

There’s so much in store, you can practically hear the binding of the program straining to contain it all.

If there is a dominant theme at this year’s conference, it’s health information technology (IT), which will be featured in a new track that will span electronic medical records, using IT for documentation and shifting from volume to value, and social media. The keynote address will cover health IT as well.

But even a quick glance captures the diversity of the program: applying for jobs, inpatient management, apps, cost-value questions, ischemic stroke, X-ray, endocrinology, and dying and the counseling of families.

Better buckle up.

Here’s some of what you need to know:

• There will be new tracks on health IT for the hospitalist, the doctor-patient relationship, post-acute care, and perioperative medicine.
• The popular “Young Hospitalist” track is back after a successful debut last year. This track covers, among other things, the application process, how to be a good mentee, how to negotiate a first job, and an introduction to quality improvement projects.

  

• To kick off the meeting, a panel will discuss the field’s expansion, or “hospital medicine at the edges.” It will feature big names, including Laurence Wellikson, MD, MHM, SHM’s chief executive officer.
• Keynote speaker Karen DeSalvo, MD, MPH, MSc, national coordinator for health information technology and acting assistant secretary for the U.S. Department of Health & Human Services, will discuss hospital medicine and technology.
• A series of 90-minute workshops will tackle thought-provoking and relevant topics: “Rule Your Inbox, Rule Your Life”; “Attending 101: Everything You Want and Need to Know”; and “Case-Based Discussion of Essential Issues on Anticoagulation Management.”

Plus, the tracks that form a kind of foundation for the meeting—practice management, academic/research, pediatrics, and quality improvement—will be back.

Get some tips on things to do in San Diego at HM16.

“The annual meeting will have the core content that brings hospitalists back year after year, including something for practice administrators and leaders of practice groups [with] the practice management track, including academics and researchers for the academic and research track, and a quality track for all those [involved in quality projects], and many, many hospitalists are engaged in quality and patient safety efforts across the country,” says Course Director Melissa Mattison, MD, SFHM, assistant professor of medicine at Harvard Medical School in Boston.

The panel on hospital expansion will cover four main areas that are seeing rapid change, according to Dr. Wellikson.

“Hospitalists continue to see their scope of practice evolve and expand,” he says. “In this presentation, we will hear from national leaders about the expanding roles of hospitalists.”

Topics will include palliative care, covered by Steve Pantilat, MD, SFHM, medical director of the University of California at San Francisco School of Medicine palliative care service; alternative payment models, covered by Ron Greeno, MD, MHM, executive vice president for strategy and innovation at Cogent Healthcare; post-acute care, covered by SHM President Bob Harrington, MD, SFHM, CMO at Reliant Post-Acute Care Solutions; and perioperative care, covered by Rachel Thompson, MD, MPH, FHM, associate professor of medicine at the University of Washington.

Dr. Mattison and other organizers thought it was imperative to bring back the “Young Hospitalist” track, which “was wildly successful last year” in both attendance and reviews.

“It’s for people who are aspiring hospitalists—medical students and residents in training—who hope to go on to hospital medicine careers, as well as people who are newly minted hospitalists, people who are probably between one and five years out of their training,” Dr. Mattison explains.

Darlene Tad-y, MD, FHM, assistant professor of medicine at University of Colorado at Denver and chair of SHM’s Physicians in Training Committee, says the offerings for young hospitalists come in response to requests from students, residents, and junior faculty. The track intends to give its audience a sense of how to apply for jobs and start shaping a career path, as well as an understanding of the contours of the hospital medicine field.

Dr. Tad-y says she wants the track to reflect her past experiences at SHM meetings (she’s been to five in a row) of a vibrant, engaged community.

“We wanted our students, residents, and young hospitalists to be able to interact with the whole spectrum of hospitalists—folks who are medical educators, folks who are group leaders, folks who are doing quality and safety work,” she says. “All of our sessions are designed to give them those opportunities.”

Hospitalists, she says, “broadly are game changers.”

“We really want our students, residents, and junior hospitalists to engage with us and see how they can be part of this,” she adds.

Dr. Mattison hopes the annual meeting continues to build on its solid reputation.

“I’ve always enjoyed the annual meeting,” she says. “There are a lot of strengths in SHM’s annual meeting year after year. I think the challenge in planning another annual meeting is building upon that strength and continuing it, and finding new topics and new tracks, and evolving with the times.” TH

Thomas R. Collins is a freelance writer in South Florida.

If you can’t find anything that interests you at HM16, check your caffeine level. You might need a cup.

There’s so much in store, you can practically hear the binding of the program straining to contain it all.

If there is a dominant theme at this year’s conference, it’s health information technology (IT), which will be featured in a new track that will span electronic medical records, using IT for documentation and shifting from volume to value, and social media. The keynote address will cover health IT as well.

But even a quick glance captures the diversity of the program: applying for jobs, inpatient management, apps, cost-value questions, ischemic stroke, X-ray, endocrinology, and dying and the counseling of families.

Better buckle up.

Here’s some of what you need to know:

• There will be new tracks on health IT for the hospitalist, the doctor-patient relationship, post-acute care, and perioperative medicine.
• The popular “Young Hospitalist” track is back after a successful debut last year. This track covers, among other things, the application process, how to be a good mentee, how to negotiate a first job, and an introduction to quality improvement projects.

  

• To kick off the meeting, a panel will discuss the field’s expansion, or “hospital medicine at the edges.” It will feature big names, including Laurence Wellikson, MD, MHM, SHM’s chief executive officer.
• Keynote speaker Karen DeSalvo, MD, MPH, MSc, national coordinator for health information technology and acting assistant secretary for the U.S. Department of Health & Human Services, will discuss hospital medicine and technology.
• A series of 90-minute workshops will tackle thought-provoking and relevant topics: “Rule Your Inbox, Rule Your Life”; “Attending 101: Everything You Want and Need to Know”; and “Case-Based Discussion of Essential Issues on Anticoagulation Management.”

Plus, the tracks that form a kind of foundation for the meeting—practice management, academic/research, pediatrics, and quality improvement—will be back.

Get some tips on things to do in San Diego at HM16.

“The annual meeting will have the core content that brings hospitalists back year after year, including something for practice administrators and leaders of practice groups [with] the practice management track, including academics and researchers for the academic and research track, and a quality track for all those [involved in quality projects], and many, many hospitalists are engaged in quality and patient safety efforts across the country,” says Course Director Melissa Mattison, MD, SFHM, assistant professor of medicine at Harvard Medical School in Boston.

The panel on hospital expansion will cover four main areas that are seeing rapid change, according to Dr. Wellikson.

“Hospitalists continue to see their scope of practice evolve and expand,” he says. “In this presentation, we will hear from national leaders about the expanding roles of hospitalists.”

Topics will include palliative care, covered by Steve Pantilat, MD, SFHM, medical director of the University of California at San Francisco School of Medicine palliative care service; alternative payment models, covered by Ron Greeno, MD, MHM, executive vice president for strategy and innovation at Cogent Healthcare; post-acute care, covered by SHM President Bob Harrington, MD, SFHM, CMO at Reliant Post-Acute Care Solutions; and perioperative care, covered by Rachel Thompson, MD, MPH, FHM, associate professor of medicine at the University of Washington.

Dr. Mattison and other organizers thought it was imperative to bring back the “Young Hospitalist” track, which “was wildly successful last year” in both attendance and reviews.

“It’s for people who are aspiring hospitalists—medical students and residents in training—who hope to go on to hospital medicine careers, as well as people who are newly minted hospitalists, people who are probably between one and five years out of their training,” Dr. Mattison explains.

Darlene Tad-y, MD, FHM, assistant professor of medicine at University of Colorado at Denver and chair of SHM’s Physicians in Training Committee, says the offerings for young hospitalists come in response to requests from students, residents, and junior faculty. The track intends to give its audience a sense of how to apply for jobs and start shaping a career path, as well as an understanding of the contours of the hospital medicine field.

Dr. Tad-y says she wants the track to reflect her past experiences at SHM meetings (she’s been to five in a row) of a vibrant, engaged community.

“We wanted our students, residents, and young hospitalists to be able to interact with the whole spectrum of hospitalists—folks who are medical educators, folks who are group leaders, folks who are doing quality and safety work,” she says. “All of our sessions are designed to give them those opportunities.”

Hospitalists, she says, “broadly are game changers.”

“We really want our students, residents, and junior hospitalists to engage with us and see how they can be part of this,” she adds.

Dr. Mattison hopes the annual meeting continues to build on its solid reputation.

“I’ve always enjoyed the annual meeting,” she says. “There are a lot of strengths in SHM’s annual meeting year after year. I think the challenge in planning another annual meeting is building upon that strength and continuing it, and finding new topics and new tracks, and evolving with the times.” TH

Thomas R. Collins is a freelance writer in South Florida.

If you can’t find anything that interests you at HM16, check your caffeine level. You might need a cup.

There’s so much in store, you can practically hear the binding of the program straining to contain it all.

If there is a dominant theme at this year’s conference, it’s health information technology (IT), which will be featured in a new track that will span electronic medical records, using IT for documentation and shifting from volume to value, and social media. The keynote address will cover health IT as well.

But even a quick glance captures the diversity of the program: applying for jobs, inpatient management, apps, cost-value questions, ischemic stroke, X-ray, endocrinology, and dying and the counseling of families.

Better buckle up.

Here’s some of what you need to know:

• There will be new tracks on health IT for the hospitalist, the doctor-patient relationship, post-acute care, and perioperative medicine.
• The popular “Young Hospitalist” track is back after a successful debut last year. This track covers, among other things, the application process, how to be a good mentee, how to negotiate a first job, and an introduction to quality improvement projects.

  

• To kick off the meeting, a panel will discuss the field’s expansion, or “hospital medicine at the edges.” It will feature big names, including Laurence Wellikson, MD, MHM, SHM’s chief executive officer.
• Keynote speaker Karen DeSalvo, MD, MPH, MSc, national coordinator for health information technology and acting assistant secretary for the U.S. Department of Health & Human Services, will discuss hospital medicine and technology.
• A series of 90-minute workshops will tackle thought-provoking and relevant topics: “Rule Your Inbox, Rule Your Life”; “Attending 101: Everything You Want and Need to Know”; and “Case-Based Discussion of Essential Issues on Anticoagulation Management.”

Plus, the tracks that form a kind of foundation for the meeting—practice management, academic/research, pediatrics, and quality improvement—will be back.

Get some tips on things to do in San Diego at HM16.

“The annual meeting will have the core content that brings hospitalists back year after year, including something for practice administrators and leaders of practice groups [with] the practice management track, including academics and researchers for the academic and research track, and a quality track for all those [involved in quality projects], and many, many hospitalists are engaged in quality and patient safety efforts across the country,” says Course Director Melissa Mattison, MD, SFHM, assistant professor of medicine at Harvard Medical School in Boston.

The panel on hospital expansion will cover four main areas that are seeing rapid change, according to Dr. Wellikson.

“Hospitalists continue to see their scope of practice evolve and expand,” he says. “In this presentation, we will hear from national leaders about the expanding roles of hospitalists.”

Topics will include palliative care, covered by Steve Pantilat, MD, SFHM, medical director of the University of California at San Francisco School of Medicine palliative care service; alternative payment models, covered by Ron Greeno, MD, MHM, executive vice president for strategy and innovation at Cogent Healthcare; post-acute care, covered by SHM President Bob Harrington, MD, SFHM, CMO at Reliant Post-Acute Care Solutions; and perioperative care, covered by Rachel Thompson, MD, MPH, FHM, associate professor of medicine at the University of Washington.

Dr. Mattison and other organizers thought it was imperative to bring back the “Young Hospitalist” track, which “was wildly successful last year” in both attendance and reviews.

“It’s for people who are aspiring hospitalists—medical students and residents in training—who hope to go on to hospital medicine careers, as well as people who are newly minted hospitalists, people who are probably between one and five years out of their training,” Dr. Mattison explains.

Darlene Tad-y, MD, FHM, assistant professor of medicine at University of Colorado at Denver and chair of SHM’s Physicians in Training Committee, says the offerings for young hospitalists come in response to requests from students, residents, and junior faculty. The track intends to give its audience a sense of how to apply for jobs and start shaping a career path, as well as an understanding of the contours of the hospital medicine field.

Dr. Tad-y says she wants the track to reflect her past experiences at SHM meetings (she’s been to five in a row) of a vibrant, engaged community.

“We wanted our students, residents, and young hospitalists to be able to interact with the whole spectrum of hospitalists—folks who are medical educators, folks who are group leaders, folks who are doing quality and safety work,” she says. “All of our sessions are designed to give them those opportunities.”

Hospitalists, she says, “broadly are game changers.”

“We really want our students, residents, and junior hospitalists to engage with us and see how they can be part of this,” she adds.

Dr. Mattison hopes the annual meeting continues to build on its solid reputation.

“I’ve always enjoyed the annual meeting,” she says. “There are a lot of strengths in SHM’s annual meeting year after year. I think the challenge in planning another annual meeting is building upon that strength and continuing it, and finding new topics and new tracks, and evolving with the times.” TH

Thomas R. Collins is a freelance writer in South Florida.

Unlike the crowded Republican primary field heading into this year’s presidential election, just three candidates seek the Democratic nomination: former First Lady and former New York Sen. Hillary Clinton, former Maryland Gov. Martin O’Malley, and U.S. Sen. Bernie Sanders of Vermont.

Although they share numerous ideas, the candidates also differ fundamentally in how they believe the American healthcare system should be run. And they stand in stark contrast to their Republican opponents.

“There really is a philosophical difference between the parties,” says Robert Blendon, professor of health policy and political analysis at the Harvard T.H. Chan School of Public Health and Harvard Kennedy School of Government. “Republicans really feel that if people themselves controlled more of the financial wherewithal, they would shop more and ask more questions.”

Democrats, however, “tend to believe that when people are ill, they are not in particularly good shape to shop,” Blendon says. Nor are they particularly fit to decide what costs are worth incurring or what procedures they may or may not need, he adds.

Listen to more of our interview with Dr. Blendon.

In general, Democrats believe the healthcare system should provide patients structure to make appropriate choices. They do not support reliance on high-deductible health plans and health savings accounts to lower healthcare costs.

“This is why the outcome of the election will matter,” Blendon says, “because it’s a very different view of what the future should look like.”

In 1993, as First Lady, Clinton undertook a failed but massive healthcare reform effort that would have created a universal healthcare system based on private insurance. Today, she supports the Affordable Care Act and says she will continue to build upon and support it, which includes making changes to the law such as repealing the Cadillac tax and further lowering out-of-pocket healthcare costs for most Americans.

Clinton’s view “is that many people have too large deductibles and copays, and for moderate-income people, it’s really deterring care,” Blendon says. “She’s likely to try to see if they can actually increase the government subsidies so the plans offer a wider range of benefits.”

Bradley Flansbaum, DO, MPH, MHM, hospitalist and SHM Public Policy Committee member, says changes must be made.

“We can’t say the direction we’re moving in is the right direction,” he says. “There is a desperate sense in America that what we have been doing is wrong and we need to change … whether the experiments now lead to a system more Americans would prefer remains to be seen.”

Sanders believes in a much bolder shift in direction. He does not think the Affordable Care Act goes far enough and wants to move to a single-payor system.

“I want to end the international embarrassment of the United States of America being the only major country on Earth that doesn’t guarantee healthcare to all people as a right, not a privilege,” he said at the second Democratic debate on Nov. 14, 2015.

However, his vision is unlikely to come to quick fruition if elected, Blendon says. “There’s not going to be—anywhere in the short term—the votes in the U.S. Congress to move in that direction.

“But it would change the level of discussion.”

O’Malley, on the other hand, wants to expand the ACA and envisions an “all-payor system” like that in Maryland, where the state sets medical costs and caps what hospitals can charge. He has vowed to continue to move away from a fee-for-service healthcare system and has said that reform should “eliminate the profit motive” for hospitals CEOs to keep beds filled.

“Regardless of who is elected, I would like to believe they would build off of what already exists,” says Joshua Lenchus, DO, RPh, SFHM, a member of SHM’s Public Policy Committee and a hospitalist at the University of Miami Jackson Memorial Hospital. “The populace doesn’t have the stomach for going through healthcare reform again.”

One of the biggest issues to emerge in the Democratic primaries is drugs: the pricing set by and regulations governing the pharmaceutical industry. Sanders wants to see a higher level of transparency, Clinton wants to require companies receiving federal support to invest in research, and both want to see the skyrocketing costs of prescription drugs reduced dramatically. This includes allowing Medicare to negotiate drug prices and allowing the sale of drugs from other countries that meet FDA standards.

“That resonates with the general public,” Blendon says, “because it’s very hard for people to understand that if we’re free trade in everything, why aren’t we for free trade in pharmaceuticals?”

Dr. Lenchus believes Democrats are going to “double-down” on health reform.

“To ensure the financial underpinnings and some of the partisan concerns are addressed,” he says. “I think with respect to hospitalists, the thing that impacts us the most is how medicine is going to get paid for doing what it does.” TH

Kelly April Tyrrell is a freelance writer in Madison, Wis.

Unlike the crowded Republican primary field heading into this year’s presidential election, just three candidates seek the Democratic nomination: former First Lady and former New York Sen. Hillary Clinton, former Maryland Gov. Martin O’Malley, and U.S. Sen. Bernie Sanders of Vermont.

Although they share numerous ideas, the candidates also differ fundamentally in how they believe the American healthcare system should be run. And they stand in stark contrast to their Republican opponents.

“There really is a philosophical difference between the parties,” says Robert Blendon, professor of health policy and political analysis at the Harvard T.H. Chan School of Public Health and Harvard Kennedy School of Government. “Republicans really feel that if people themselves controlled more of the financial wherewithal, they would shop more and ask more questions.”

Democrats, however, “tend to believe that when people are ill, they are not in particularly good shape to shop,” Blendon says. Nor are they particularly fit to decide what costs are worth incurring or what procedures they may or may not need, he adds.

Listen to more of our interview with Dr. Blendon.

In general, Democrats believe the healthcare system should provide patients structure to make appropriate choices. They do not support reliance on high-deductible health plans and health savings accounts to lower healthcare costs.

“This is why the outcome of the election will matter,” Blendon says, “because it’s a very different view of what the future should look like.”

In 1993, as First Lady, Clinton undertook a failed but massive healthcare reform effort that would have created a universal healthcare system based on private insurance. Today, she supports the Affordable Care Act and says she will continue to build upon and support it, which includes making changes to the law such as repealing the Cadillac tax and further lowering out-of-pocket healthcare costs for most Americans.

Clinton’s view “is that many people have too large deductibles and copays, and for moderate-income people, it’s really deterring care,” Blendon says. “She’s likely to try to see if they can actually increase the government subsidies so the plans offer a wider range of benefits.”

Bradley Flansbaum, DO, MPH, MHM, hospitalist and SHM Public Policy Committee member, says changes must be made.

“We can’t say the direction we’re moving in is the right direction,” he says. “There is a desperate sense in America that what we have been doing is wrong and we need to change … whether the experiments now lead to a system more Americans would prefer remains to be seen.”

Sanders believes in a much bolder shift in direction. He does not think the Affordable Care Act goes far enough and wants to move to a single-payor system.

“I want to end the international embarrassment of the United States of America being the only major country on Earth that doesn’t guarantee healthcare to all people as a right, not a privilege,” he said at the second Democratic debate on Nov. 14, 2015.

However, his vision is unlikely to come to quick fruition if elected, Blendon says. “There’s not going to be—anywhere in the short term—the votes in the U.S. Congress to move in that direction.

“But it would change the level of discussion.”

O’Malley, on the other hand, wants to expand the ACA and envisions an “all-payor system” like that in Maryland, where the state sets medical costs and caps what hospitals can charge. He has vowed to continue to move away from a fee-for-service healthcare system and has said that reform should “eliminate the profit motive” for hospitals CEOs to keep beds filled.

“Regardless of who is elected, I would like to believe they would build off of what already exists,” says Joshua Lenchus, DO, RPh, SFHM, a member of SHM’s Public Policy Committee and a hospitalist at the University of Miami Jackson Memorial Hospital. “The populace doesn’t have the stomach for going through healthcare reform again.”

One of the biggest issues to emerge in the Democratic primaries is drugs: the pricing set by and regulations governing the pharmaceutical industry. Sanders wants to see a higher level of transparency, Clinton wants to require companies receiving federal support to invest in research, and both want to see the skyrocketing costs of prescription drugs reduced dramatically. This includes allowing Medicare to negotiate drug prices and allowing the sale of drugs from other countries that meet FDA standards.

“That resonates with the general public,” Blendon says, “because it’s very hard for people to understand that if we’re free trade in everything, why aren’t we for free trade in pharmaceuticals?”

Dr. Lenchus believes Democrats are going to “double-down” on health reform.

“To ensure the financial underpinnings and some of the partisan concerns are addressed,” he says. “I think with respect to hospitalists, the thing that impacts us the most is how medicine is going to get paid for doing what it does.” TH

Kelly April Tyrrell is a freelance writer in Madison, Wis.

Unlike the crowded Republican primary field heading into this year’s presidential election, just three candidates seek the Democratic nomination: former First Lady and former New York Sen. Hillary Clinton, former Maryland Gov. Martin O’Malley, and U.S. Sen. Bernie Sanders of Vermont.

Although they share numerous ideas, the candidates also differ fundamentally in how they believe the American healthcare system should be run. And they stand in stark contrast to their Republican opponents.

“There really is a philosophical difference between the parties,” says Robert Blendon, professor of health policy and political analysis at the Harvard T.H. Chan School of Public Health and Harvard Kennedy School of Government. “Republicans really feel that if people themselves controlled more of the financial wherewithal, they would shop more and ask more questions.”

Democrats, however, “tend to believe that when people are ill, they are not in particularly good shape to shop,” Blendon says. Nor are they particularly fit to decide what costs are worth incurring or what procedures they may or may not need, he adds.

Listen to more of our interview with Dr. Blendon.

In general, Democrats believe the healthcare system should provide patients structure to make appropriate choices. They do not support reliance on high-deductible health plans and health savings accounts to lower healthcare costs.

“This is why the outcome of the election will matter,” Blendon says, “because it’s a very different view of what the future should look like.”

In 1993, as First Lady, Clinton undertook a failed but massive healthcare reform effort that would have created a universal healthcare system based on private insurance. Today, she supports the Affordable Care Act and says she will continue to build upon and support it, which includes making changes to the law such as repealing the Cadillac tax and further lowering out-of-pocket healthcare costs for most Americans.

Clinton’s view “is that many people have too large deductibles and copays, and for moderate-income people, it’s really deterring care,” Blendon says. “She’s likely to try to see if they can actually increase the government subsidies so the plans offer a wider range of benefits.”

Bradley Flansbaum, DO, MPH, MHM, hospitalist and SHM Public Policy Committee member, says changes must be made.

“We can’t say the direction we’re moving in is the right direction,” he says. “There is a desperate sense in America that what we have been doing is wrong and we need to change … whether the experiments now lead to a system more Americans would prefer remains to be seen.”

Sanders believes in a much bolder shift in direction. He does not think the Affordable Care Act goes far enough and wants to move to a single-payor system.

“I want to end the international embarrassment of the United States of America being the only major country on Earth that doesn’t guarantee healthcare to all people as a right, not a privilege,” he said at the second Democratic debate on Nov. 14, 2015.

However, his vision is unlikely to come to quick fruition if elected, Blendon says. “There’s not going to be—anywhere in the short term—the votes in the U.S. Congress to move in that direction.

“But it would change the level of discussion.”

O’Malley, on the other hand, wants to expand the ACA and envisions an “all-payor system” like that in Maryland, where the state sets medical costs and caps what hospitals can charge. He has vowed to continue to move away from a fee-for-service healthcare system and has said that reform should “eliminate the profit motive” for hospitals CEOs to keep beds filled.

“Regardless of who is elected, I would like to believe they would build off of what already exists,” says Joshua Lenchus, DO, RPh, SFHM, a member of SHM’s Public Policy Committee and a hospitalist at the University of Miami Jackson Memorial Hospital. “The populace doesn’t have the stomach for going through healthcare reform again.”

One of the biggest issues to emerge in the Democratic primaries is drugs: the pricing set by and regulations governing the pharmaceutical industry. Sanders wants to see a higher level of transparency, Clinton wants to require companies receiving federal support to invest in research, and both want to see the skyrocketing costs of prescription drugs reduced dramatically. This includes allowing Medicare to negotiate drug prices and allowing the sale of drugs from other countries that meet FDA standards.

“That resonates with the general public,” Blendon says, “because it’s very hard for people to understand that if we’re free trade in everything, why aren’t we for free trade in pharmaceuticals?”

Dr. Lenchus believes Democrats are going to “double-down” on health reform.

“To ensure the financial underpinnings and some of the partisan concerns are addressed,” he says. “I think with respect to hospitalists, the thing that impacts us the most is how medicine is going to get paid for doing what it does.” TH

Kelly April Tyrrell is a freelance writer in Madison, Wis.

Lab mouse

The protein kinase CHK1 may be a therapeutic target for Fanconi anemia (FA), according to researchers.

They studied induced pluripotent stem cells (iPSCs) derived from FA patients and found the FA DNA repair pathway was essential for the cells’ proliferation and survival.

The team also discovered that CHK1 played a “crucial” role in iPSCs’ sensitivity to accrued DNA damage, and inhibiting CHK1 allowed FA-deficient iPSCs to grow

normally.

The team relayed these findings in Stem Cell Reports.

“This study provides an experimental platform to test new therapies that could prevent pre- and post-natal Fanconi anemia conditions, which have no cure and limited treatment options,” said study author Susanne Wells, PhD, of the Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings also raise a number of important questions, so there is a lot more to be done.”

For this study, Dr Wells and her colleagues used iPSCs reprogrammed from mature skin and connective tissue cells donated by FA patients. The cells had a defective FA DNA repair pathway.

The researchers studied the iPSCs in culture and injected them into humanized mouse models, monitoring their genetic, molecular, and developmental progression.

Even with defective FA DNA repair, the iPSCs retained their ability to transform into different tissues, and humanized mice injected with the defective cells started to form teratomas.

However, the DNA repair defect started to kill off the iPSCs by blocking cell division and causing apoptosis.

The researchers noticed that CHK1, which serves as a DNA regulatory checkpoint during cell division, was hyperactive in the iPSCs, which hastened their death.

So the team used pharmacologic inhibitors of CHK1 to block the hyperactive enzyme at a critical stage of the stem cell cycle. This allowed them to override what are usually unfixable errors in the FA repair pathway.

After targeted treatment, FA-pathway-deficient iPSCs resumed dividing and expanding normally.

The researchers said that, to their surprise, the resumption of cell growth occurred without what they had expected to be massive chromosome abnormalities. Because of this, they speculate that a compensating DNA repair process is engaged in the reinvigorated cells.

Because this unidentified repair process may also rescue the DNA repair defect in the different tissue types affected by FA, Dr Wells and her colleagues believe their study may point to an approach that treats all clinical manifestations of the disease, including anemia and cancer.

“A key question for us is, ‘What type of DNA repair kicks in under these conditions, and is it error-free or error-prone?’” Dr Wells explained. “A novel mode of emergency DNA repair might indeed be discovered in the [iPSCs]. We believe some type of compensatory DNA repair must be driven by CHK1 inhibition when cells have FA pathway loss. Otherwise, the cells would have died off very quickly.”

The researchers plan to follow up this study with additional testing in humanized and genetic mouse models. They said they will attempt to improve embryonic development and post-birth fitness in FA-pathway-deficient mice with timed application of a CHK1 inhibitor.

The team will monitor the mice as they age and use genetic sequencing to screen for disease-causing mutations. And they will look for evidence of a DNA repair process (either novel or existing) in the FA-deficient mice.

Lab mouse

The protein kinase CHK1 may be a therapeutic target for Fanconi anemia (FA), according to researchers.

They studied induced pluripotent stem cells (iPSCs) derived from FA patients and found the FA DNA repair pathway was essential for the cells’ proliferation and survival.

The team also discovered that CHK1 played a “crucial” role in iPSCs’ sensitivity to accrued DNA damage, and inhibiting CHK1 allowed FA-deficient iPSCs to grow

normally.

The team relayed these findings in Stem Cell Reports.

“This study provides an experimental platform to test new therapies that could prevent pre- and post-natal Fanconi anemia conditions, which have no cure and limited treatment options,” said study author Susanne Wells, PhD, of the Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings also raise a number of important questions, so there is a lot more to be done.”

For this study, Dr Wells and her colleagues used iPSCs reprogrammed from mature skin and connective tissue cells donated by FA patients. The cells had a defective FA DNA repair pathway.

The researchers studied the iPSCs in culture and injected them into humanized mouse models, monitoring their genetic, molecular, and developmental progression.

Even with defective FA DNA repair, the iPSCs retained their ability to transform into different tissues, and humanized mice injected with the defective cells started to form teratomas.

However, the DNA repair defect started to kill off the iPSCs by blocking cell division and causing apoptosis.

The researchers noticed that CHK1, which serves as a DNA regulatory checkpoint during cell division, was hyperactive in the iPSCs, which hastened their death.

So the team used pharmacologic inhibitors of CHK1 to block the hyperactive enzyme at a critical stage of the stem cell cycle. This allowed them to override what are usually unfixable errors in the FA repair pathway.

After targeted treatment, FA-pathway-deficient iPSCs resumed dividing and expanding normally.

The researchers said that, to their surprise, the resumption of cell growth occurred without what they had expected to be massive chromosome abnormalities. Because of this, they speculate that a compensating DNA repair process is engaged in the reinvigorated cells.

Because this unidentified repair process may also rescue the DNA repair defect in the different tissue types affected by FA, Dr Wells and her colleagues believe their study may point to an approach that treats all clinical manifestations of the disease, including anemia and cancer.

“A key question for us is, ‘What type of DNA repair kicks in under these conditions, and is it error-free or error-prone?’” Dr Wells explained. “A novel mode of emergency DNA repair might indeed be discovered in the [iPSCs]. We believe some type of compensatory DNA repair must be driven by CHK1 inhibition when cells have FA pathway loss. Otherwise, the cells would have died off very quickly.”

The researchers plan to follow up this study with additional testing in humanized and genetic mouse models. They said they will attempt to improve embryonic development and post-birth fitness in FA-pathway-deficient mice with timed application of a CHK1 inhibitor.

The team will monitor the mice as they age and use genetic sequencing to screen for disease-causing mutations. And they will look for evidence of a DNA repair process (either novel or existing) in the FA-deficient mice.

Lab mouse

The protein kinase CHK1 may be a therapeutic target for Fanconi anemia (FA), according to researchers.

They studied induced pluripotent stem cells (iPSCs) derived from FA patients and found the FA DNA repair pathway was essential for the cells’ proliferation and survival.

The team also discovered that CHK1 played a “crucial” role in iPSCs’ sensitivity to accrued DNA damage, and inhibiting CHK1 allowed FA-deficient iPSCs to grow

normally.

The team relayed these findings in Stem Cell Reports.

“This study provides an experimental platform to test new therapies that could prevent pre- and post-natal Fanconi anemia conditions, which have no cure and limited treatment options,” said study author Susanne Wells, PhD, of the Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings also raise a number of important questions, so there is a lot more to be done.”

For this study, Dr Wells and her colleagues used iPSCs reprogrammed from mature skin and connective tissue cells donated by FA patients. The cells had a defective FA DNA repair pathway.

The researchers studied the iPSCs in culture and injected them into humanized mouse models, monitoring their genetic, molecular, and developmental progression.

Even with defective FA DNA repair, the iPSCs retained their ability to transform into different tissues, and humanized mice injected with the defective cells started to form teratomas.

However, the DNA repair defect started to kill off the iPSCs by blocking cell division and causing apoptosis.

The researchers noticed that CHK1, which serves as a DNA regulatory checkpoint during cell division, was hyperactive in the iPSCs, which hastened their death.

So the team used pharmacologic inhibitors of CHK1 to block the hyperactive enzyme at a critical stage of the stem cell cycle. This allowed them to override what are usually unfixable errors in the FA repair pathway.

After targeted treatment, FA-pathway-deficient iPSCs resumed dividing and expanding normally.

The researchers said that, to their surprise, the resumption of cell growth occurred without what they had expected to be massive chromosome abnormalities. Because of this, they speculate that a compensating DNA repair process is engaged in the reinvigorated cells.

Because this unidentified repair process may also rescue the DNA repair defect in the different tissue types affected by FA, Dr Wells and her colleagues believe their study may point to an approach that treats all clinical manifestations of the disease, including anemia and cancer.

“A key question for us is, ‘What type of DNA repair kicks in under these conditions, and is it error-free or error-prone?’” Dr Wells explained. “A novel mode of emergency DNA repair might indeed be discovered in the [iPSCs]. We believe some type of compensatory DNA repair must be driven by CHK1 inhibition when cells have FA pathway loss. Otherwise, the cells would have died off very quickly.”

The researchers plan to follow up this study with additional testing in humanized and genetic mouse models. They said they will attempt to improve embryonic development and post-birth fitness in FA-pathway-deficient mice with timed application of a CHK1 inhibitor.

The team will monitor the mice as they age and use genetic sequencing to screen for disease-causing mutations. And they will look for evidence of a DNA repair process (either novel or existing) in the FA-deficient mice.

T cells

Image courtesy of NIAID

A protein called diacylglycerol kinase alpha (DGKα) could be a therapeutic target for X-linked lymphoproliferative disease (XLP-1), according to research published in Science Translational Medicine.

Researchers have known for some time that XLP-1 is a heritable disorder caused by germline mutations in SH2D1A.

When this gene is affected, it leads to defects in an adaptor molecule known as SAP (signaling lymphocytic activation molecule-associated protein), which regulates T-cell receptor signaling and triggers cytotoxic T cells to self-destruct when they are no longer needed.

Without an effective SAP adaptor molecule, apoptosis is impaired, and DGKα is activated.

With the current study, researchers wanted to determine whether the over-activation of DGKα might contribute to the reduced apoptosis observed in T cells in patients with XLP-1 and the accumulation of T cells that occurs following infection with Epstein-Barr virus.

“Patients with X-linked lymphoproliferative disease are prone to severe Epstein-Barr virus infection due to a weakened immune system,” explained study author Kim Nichols, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Infection with Epstein-Barr virus can have potentially fatal consequences for these patients. This severe disease is a double-edged sword. On the one hand, the immune system is significantly weakened. However, detrimental side effects occur due to the expansion and hyper-activation of T cells.”

“[W]e wanted to establish the biochemical mechanism underlying these changes so that we could develop better treatments for X-linked lymphoproliferative disease patients experiencing hyper-inflammation.”

Studying T cells from XLP-1 patients, the researchers found that SAP and DGKα are both crucial for the regulation of T-cell death. Loss of SAP, which normally inhibits DGKα, led to unrestrained DGKα activity, resulting in impaired T-cell receptor signaling and resistance to apoptosis.

Pharmacologic inhibition of DGKα restored the sensitivity of XLP-1 T cells to cell death. Using small interfering RNA to knockout DGKα in cultured XLP-1 T cells had the same results.

And pharmacologic inhibition of DGKα curtailed the expansion of T cells in virus-infected mice that served as a model organism to study XLP-1.

Treating the mice with a DGKα inhibitor restored T cells’ sensitivity to cell death by boosting the expression of pro-apoptotic proteins, which prevented excessive T-cell buildup and reduced the severity of the disease.

“Our findings suggest that inhibition of DGKα could reverse some of the life-threatening effects linked to Epstein-Barr virus infection of patients with X-linked lymphoproliferative disease,” Dr Nichols concluded.

T cells

Image courtesy of NIAID

A protein called diacylglycerol kinase alpha (DGKα) could be a therapeutic target for X-linked lymphoproliferative disease (XLP-1), according to research published in Science Translational Medicine.

Researchers have known for some time that XLP-1 is a heritable disorder caused by germline mutations in SH2D1A.

When this gene is affected, it leads to defects in an adaptor molecule known as SAP (signaling lymphocytic activation molecule-associated protein), which regulates T-cell receptor signaling and triggers cytotoxic T cells to self-destruct when they are no longer needed.

Without an effective SAP adaptor molecule, apoptosis is impaired, and DGKα is activated.

With the current study, researchers wanted to determine whether the over-activation of DGKα might contribute to the reduced apoptosis observed in T cells in patients with XLP-1 and the accumulation of T cells that occurs following infection with Epstein-Barr virus.

“Patients with X-linked lymphoproliferative disease are prone to severe Epstein-Barr virus infection due to a weakened immune system,” explained study author Kim Nichols, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Infection with Epstein-Barr virus can have potentially fatal consequences for these patients. This severe disease is a double-edged sword. On the one hand, the immune system is significantly weakened. However, detrimental side effects occur due to the expansion and hyper-activation of T cells.”

“[W]e wanted to establish the biochemical mechanism underlying these changes so that we could develop better treatments for X-linked lymphoproliferative disease patients experiencing hyper-inflammation.”

Studying T cells from XLP-1 patients, the researchers found that SAP and DGKα are both crucial for the regulation of T-cell death. Loss of SAP, which normally inhibits DGKα, led to unrestrained DGKα activity, resulting in impaired T-cell receptor signaling and resistance to apoptosis.

Pharmacologic inhibition of DGKα restored the sensitivity of XLP-1 T cells to cell death. Using small interfering RNA to knockout DGKα in cultured XLP-1 T cells had the same results.

And pharmacologic inhibition of DGKα curtailed the expansion of T cells in virus-infected mice that served as a model organism to study XLP-1.

Treating the mice with a DGKα inhibitor restored T cells’ sensitivity to cell death by boosting the expression of pro-apoptotic proteins, which prevented excessive T-cell buildup and reduced the severity of the disease.

“Our findings suggest that inhibition of DGKα could reverse some of the life-threatening effects linked to Epstein-Barr virus infection of patients with X-linked lymphoproliferative disease,” Dr Nichols concluded.

T cells

Image courtesy of NIAID

A protein called diacylglycerol kinase alpha (DGKα) could be a therapeutic target for X-linked lymphoproliferative disease (XLP-1), according to research published in Science Translational Medicine.

Researchers have known for some time that XLP-1 is a heritable disorder caused by germline mutations in SH2D1A.

When this gene is affected, it leads to defects in an adaptor molecule known as SAP (signaling lymphocytic activation molecule-associated protein), which regulates T-cell receptor signaling and triggers cytotoxic T cells to self-destruct when they are no longer needed.

Without an effective SAP adaptor molecule, apoptosis is impaired, and DGKα is activated.

With the current study, researchers wanted to determine whether the over-activation of DGKα might contribute to the reduced apoptosis observed in T cells in patients with XLP-1 and the accumulation of T cells that occurs following infection with Epstein-Barr virus.

“Patients with X-linked lymphoproliferative disease are prone to severe Epstein-Barr virus infection due to a weakened immune system,” explained study author Kim Nichols, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Infection with Epstein-Barr virus can have potentially fatal consequences for these patients. This severe disease is a double-edged sword. On the one hand, the immune system is significantly weakened. However, detrimental side effects occur due to the expansion and hyper-activation of T cells.”

“[W]e wanted to establish the biochemical mechanism underlying these changes so that we could develop better treatments for X-linked lymphoproliferative disease patients experiencing hyper-inflammation.”

Studying T cells from XLP-1 patients, the researchers found that SAP and DGKα are both crucial for the regulation of T-cell death. Loss of SAP, which normally inhibits DGKα, led to unrestrained DGKα activity, resulting in impaired T-cell receptor signaling and resistance to apoptosis.

Pharmacologic inhibition of DGKα restored the sensitivity of XLP-1 T cells to cell death. Using small interfering RNA to knockout DGKα in cultured XLP-1 T cells had the same results.

And pharmacologic inhibition of DGKα curtailed the expansion of T cells in virus-infected mice that served as a model organism to study XLP-1.

Treating the mice with a DGKα inhibitor restored T cells’ sensitivity to cell death by boosting the expression of pro-apoptotic proteins, which prevented excessive T-cell buildup and reduced the severity of the disease.

“Our findings suggest that inhibition of DGKα could reverse some of the life-threatening effects linked to Epstein-Barr virus infection of patients with X-linked lymphoproliferative disease,” Dr Nichols concluded.

Erik Malmström

Photo by Ingela Björck

Researchers have reported using mass spectrometry to measure hundreds of proteins in a single blood sample.

And they used the resulting protein patterns to determine the severity of sepsis in animal models. They were also able to determine which organs had been damaged in these mice.

The researchers said they’ve been able to map the majority of proteins found in vital organs and list which proteins are specific to each organ.

“If you see in a blood sample that the amount of proteins from a specific organ increases, it indicates damage to this organ,” explained study author Erik Malmström, of Lund University in Sweden.

“The method provides an understanding of the molecular events that take place during the course of a disease and the possibility, using the same analysis, to study how different organs are affected.”

The researchers described this work in Nature Communications.

The group believes their study of hundreds of different proteins could eventually be used to select other important proteins that can serve as biomarkers for different aspects of sepsis.

First and foremost, however, they think their method will be an important research tool.

“There is so much we don’t know about sepsis,” Malmström said. “Why do not all patients react the same way? Why do some organs suffer the most damage in some patients and not in others? Do different bacteria cause the disease to progress? Can you divide patients into different subgroups, or bacteria, or does each new combination of patients and bacteria lead to a specific form of sepsis?”

The current study was conducted in animals, but the researchers are now moving on to human tissue. They have obtained samples of healthy tissue from various organs and are comparing protein patterns of these samples with patterns in corresponding tissues from sepsis patients.

Erik Malmström

Photo by Ingela Björck

Researchers have reported using mass spectrometry to measure hundreds of proteins in a single blood sample.

And they used the resulting protein patterns to determine the severity of sepsis in animal models. They were also able to determine which organs had been damaged in these mice.

The researchers said they’ve been able to map the majority of proteins found in vital organs and list which proteins are specific to each organ.

“If you see in a blood sample that the amount of proteins from a specific organ increases, it indicates damage to this organ,” explained study author Erik Malmström, of Lund University in Sweden.

“The method provides an understanding of the molecular events that take place during the course of a disease and the possibility, using the same analysis, to study how different organs are affected.”

The researchers described this work in Nature Communications.

The group believes their study of hundreds of different proteins could eventually be used to select other important proteins that can serve as biomarkers for different aspects of sepsis.

First and foremost, however, they think their method will be an important research tool.

“There is so much we don’t know about sepsis,” Malmström said. “Why do not all patients react the same way? Why do some organs suffer the most damage in some patients and not in others? Do different bacteria cause the disease to progress? Can you divide patients into different subgroups, or bacteria, or does each new combination of patients and bacteria lead to a specific form of sepsis?”

The current study was conducted in animals, but the researchers are now moving on to human tissue. They have obtained samples of healthy tissue from various organs and are comparing protein patterns of these samples with patterns in corresponding tissues from sepsis patients.

Erik Malmström

Photo by Ingela Björck

Researchers have reported using mass spectrometry to measure hundreds of proteins in a single blood sample.

And they used the resulting protein patterns to determine the severity of sepsis in animal models. They were also able to determine which organs had been damaged in these mice.

The researchers said they’ve been able to map the majority of proteins found in vital organs and list which proteins are specific to each organ.

“If you see in a blood sample that the amount of proteins from a specific organ increases, it indicates damage to this organ,” explained study author Erik Malmström, of Lund University in Sweden.

“The method provides an understanding of the molecular events that take place during the course of a disease and the possibility, using the same analysis, to study how different organs are affected.”

The researchers described this work in Nature Communications.

The group believes their study of hundreds of different proteins could eventually be used to select other important proteins that can serve as biomarkers for different aspects of sepsis.

First and foremost, however, they think their method will be an important research tool.

“There is so much we don’t know about sepsis,” Malmström said. “Why do not all patients react the same way? Why do some organs suffer the most damage in some patients and not in others? Do different bacteria cause the disease to progress? Can you divide patients into different subgroups, or bacteria, or does each new combination of patients and bacteria lead to a specific form of sepsis?”

The current study was conducted in animals, but the researchers are now moving on to human tissue. They have obtained samples of healthy tissue from various organs and are comparing protein patterns of these samples with patterns in corresponding tissues from sepsis patients.

Mick Bhatia, PhD

Photo courtesy of

McMaster University

Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).

Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.

And when both GSK-3β and GSK-3α are deleted, AML develops.

“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”

Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.

Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.

They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.

The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.

The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.

“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”

Mick Bhatia, PhD

Photo courtesy of

McMaster University

Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).

Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.

And when both GSK-3β and GSK-3α are deleted, AML develops.

“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”

Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.

Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.

They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.

The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.

The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.

“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”

Mick Bhatia, PhD

Photo courtesy of

McMaster University

Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).

Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.

And when both GSK-3β and GSK-3α are deleted, AML develops.

“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”

Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.

Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.

They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.

The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.

The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.

“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”