Question: What attracted you to become involved with SHM?

Q: How has your experience with SHM brought value to your professional career?

A: Not long after I joined, I realized that SHM features a very welcoming body of members, and it encourages regular conversation about how to solve complex problems in our continuously evolving world of healthcare delivery. What I find so valuable is that SHM provides members with ample avenues to share results, success stories, challenges, and more—whether that is at the annual meetings or through the Journal of Hospital Medicine, The Hospitalist, the Hospital Medicine Exchange (HMX), social media, and more.

As a result of this culture of inclusivity, I accepted a role on the Practice Administrators Committee and subsequently on the Practice Analysis Committee as a way to further engage with SHM and network with other hospital medicine professionals. Two SHM resources I refer to on a regular basis are the Key Principles and Characteristics of an Effective Hospital Medicine Group and the biannual State of Hospital Medicine survey. Having access to key recommendations and research about hospital medicine is critical, but knowing that it was endorsed by the society dedicated to hospital medicine added extra emphasis to its relevance.

Q: How has CHI used these resources to inform decisions about hospitalist practice and leadership?

A: The list of key principles and characteristics is especially helpful with our hospitalist dyad leadership model at CHI, in which we pair strong medical and business leaders together to collectively lead and improve each division. The two key principles we always come back to are the first two: effective leadership and engaged hospitalists. The foundation of high-quality care and financial success is engaged hospitalists, requiring a meaningful relationship between hospitalists and hospital leaders. Both strategic business and medical leadership are essential to sustaining performance. For example, by having strong leadership and engaged hospitalists, we have been able to develop and implement clinical standards based on primary evidence to improve patient outcomes. By incorporating recommendations from the key principles and characteristics, we continue to advance and evolve our model to best meet our hospitalists’—and our communities’—needs.

The State of Hospital Medicine survey is a valuable asset when we’re evaluating care teams and staffing models. Reviewing data that cover what others have done—whether it is about incorporating advanced practice clinicians (NPs and PAs) into the hospital medicine group, evaluating a nocturnist model, or looking at how others have handled differentiation of schedules—ensures we not only incorporate these best practices into our decision-making process but also allows us to consider how our processes compare to others. Tie this back in with the key characteristics, and you can understand what staffing model and resources you need to build the hospital medicine group that best fits your hospital and its local needs.

Q: SHM is celebrating the 20th anniversary of hospital medicine with the “Year of the Hospitalist.” Why do you think hospital medicine continues to experience such unparalleled growth and success?

A: Hospital medicine continues to grow because it has been proven that with a focused team of caregivers, outcomes can be much better. Everyone in the industry is trying to improve quality outcomes, optimizing the right care in the right place at the right time while accomplishing this with the highest of patient satisfaction. As a result, the bar continues to be raised. There is an increasing demand for subspecialty hospitalists, and hospitalists are also in high demand in the continuum of care, outside the walls of the hospital, to care for patients in pre- and post-acute-care settings. All of this, in addition to the shift to payment for value versus volume, increases the demand for hospitalists. TH

Brett Radler is SHM’s communications coordinator.

Question: What attracted you to become involved with SHM?

Q: How has your experience with SHM brought value to your professional career?

A: Not long after I joined, I realized that SHM features a very welcoming body of members, and it encourages regular conversation about how to solve complex problems in our continuously evolving world of healthcare delivery. What I find so valuable is that SHM provides members with ample avenues to share results, success stories, challenges, and more—whether that is at the annual meetings or through the Journal of Hospital Medicine, The Hospitalist, the Hospital Medicine Exchange (HMX), social media, and more.

As a result of this culture of inclusivity, I accepted a role on the Practice Administrators Committee and subsequently on the Practice Analysis Committee as a way to further engage with SHM and network with other hospital medicine professionals. Two SHM resources I refer to on a regular basis are the Key Principles and Characteristics of an Effective Hospital Medicine Group and the biannual State of Hospital Medicine survey. Having access to key recommendations and research about hospital medicine is critical, but knowing that it was endorsed by the society dedicated to hospital medicine added extra emphasis to its relevance.

Q: How has CHI used these resources to inform decisions about hospitalist practice and leadership?

A: The list of key principles and characteristics is especially helpful with our hospitalist dyad leadership model at CHI, in which we pair strong medical and business leaders together to collectively lead and improve each division. The two key principles we always come back to are the first two: effective leadership and engaged hospitalists. The foundation of high-quality care and financial success is engaged hospitalists, requiring a meaningful relationship between hospitalists and hospital leaders. Both strategic business and medical leadership are essential to sustaining performance. For example, by having strong leadership and engaged hospitalists, we have been able to develop and implement clinical standards based on primary evidence to improve patient outcomes. By incorporating recommendations from the key principles and characteristics, we continue to advance and evolve our model to best meet our hospitalists’—and our communities’—needs.

The State of Hospital Medicine survey is a valuable asset when we’re evaluating care teams and staffing models. Reviewing data that cover what others have done—whether it is about incorporating advanced practice clinicians (NPs and PAs) into the hospital medicine group, evaluating a nocturnist model, or looking at how others have handled differentiation of schedules—ensures we not only incorporate these best practices into our decision-making process but also allows us to consider how our processes compare to others. Tie this back in with the key characteristics, and you can understand what staffing model and resources you need to build the hospital medicine group that best fits your hospital and its local needs.

Q: SHM is celebrating the 20th anniversary of hospital medicine with the “Year of the Hospitalist.” Why do you think hospital medicine continues to experience such unparalleled growth and success?

A: Hospital medicine continues to grow because it has been proven that with a focused team of caregivers, outcomes can be much better. Everyone in the industry is trying to improve quality outcomes, optimizing the right care in the right place at the right time while accomplishing this with the highest of patient satisfaction. As a result, the bar continues to be raised. There is an increasing demand for subspecialty hospitalists, and hospitalists are also in high demand in the continuum of care, outside the walls of the hospital, to care for patients in pre- and post-acute-care settings. All of this, in addition to the shift to payment for value versus volume, increases the demand for hospitalists. TH

Brett Radler is SHM’s communications coordinator.

Question: What attracted you to become involved with SHM?

Q: How has your experience with SHM brought value to your professional career?

A: Not long after I joined, I realized that SHM features a very welcoming body of members, and it encourages regular conversation about how to solve complex problems in our continuously evolving world of healthcare delivery. What I find so valuable is that SHM provides members with ample avenues to share results, success stories, challenges, and more—whether that is at the annual meetings or through the Journal of Hospital Medicine, The Hospitalist, the Hospital Medicine Exchange (HMX), social media, and more.

As a result of this culture of inclusivity, I accepted a role on the Practice Administrators Committee and subsequently on the Practice Analysis Committee as a way to further engage with SHM and network with other hospital medicine professionals. Two SHM resources I refer to on a regular basis are the Key Principles and Characteristics of an Effective Hospital Medicine Group and the biannual State of Hospital Medicine survey. Having access to key recommendations and research about hospital medicine is critical, but knowing that it was endorsed by the society dedicated to hospital medicine added extra emphasis to its relevance.

Q: How has CHI used these resources to inform decisions about hospitalist practice and leadership?

A: The list of key principles and characteristics is especially helpful with our hospitalist dyad leadership model at CHI, in which we pair strong medical and business leaders together to collectively lead and improve each division. The two key principles we always come back to are the first two: effective leadership and engaged hospitalists. The foundation of high-quality care and financial success is engaged hospitalists, requiring a meaningful relationship between hospitalists and hospital leaders. Both strategic business and medical leadership are essential to sustaining performance. For example, by having strong leadership and engaged hospitalists, we have been able to develop and implement clinical standards based on primary evidence to improve patient outcomes. By incorporating recommendations from the key principles and characteristics, we continue to advance and evolve our model to best meet our hospitalists’—and our communities’—needs.

The State of Hospital Medicine survey is a valuable asset when we’re evaluating care teams and staffing models. Reviewing data that cover what others have done—whether it is about incorporating advanced practice clinicians (NPs and PAs) into the hospital medicine group, evaluating a nocturnist model, or looking at how others have handled differentiation of schedules—ensures we not only incorporate these best practices into our decision-making process but also allows us to consider how our processes compare to others. Tie this back in with the key characteristics, and you can understand what staffing model and resources you need to build the hospital medicine group that best fits your hospital and its local needs.

Q: SHM is celebrating the 20th anniversary of hospital medicine with the “Year of the Hospitalist.” Why do you think hospital medicine continues to experience such unparalleled growth and success?

A: Hospital medicine continues to grow because it has been proven that with a focused team of caregivers, outcomes can be much better. Everyone in the industry is trying to improve quality outcomes, optimizing the right care in the right place at the right time while accomplishing this with the highest of patient satisfaction. As a result, the bar continues to be raised. There is an increasing demand for subspecialty hospitalists, and hospitalists are also in high demand in the continuum of care, outside the walls of the hospital, to care for patients in pre- and post-acute-care settings. All of this, in addition to the shift to payment for value versus volume, increases the demand for hospitalists. TH

Brett Radler is SHM’s communications coordinator.

BALTIMORE – By 2035, U.S. cardiothoracic surgeons will see a 61% increase in the national caseload, and potentially a 121% increase in cases for each surgeon, according to a data analysis presented at the annual meeting of the American Association for Thoracic Surgery.

Using data from the American Board of Thoracic Surgery, a research team at Ohio State University performed case load calculations for 2035 based on cases per surgeon per year in 2010. The researchers estimated that the average caseload per surgeon in 2035 will be 299 cases, compared with a 2010 caseload of 135 per surgeon. This increase is not matched by the number of surgeons currently trained and certified annually.

Dr. John Ikonomidis, chief of the division of cardiothoracic surgery at the Medical University of South Carolina in Charleston, and a discussant on the presentation, said surgeon retirements and an increase in the population needing treatment have put the specialty in a bind.

“We have a bit of a crisis now, honestly, but this particular paper puts it in even further perspective,” Dr. Ikonomidis said in a video interview. “By 2035 we’re looking at a 3,000-surgeon shortage, relative to what would be available.” He noted that approximately 90 medical residents per year are certified as cardiothoracic surgeons, a rate which will not produce enough CT surgeons to meet the projected shortage.

“We need to continue to have this conversation,” he concluded. “It is a reminder that the predictions we made 15 years ago appear to be true, and we probably need to do something about it, at least in the short term.”

Dr. Ikonomidis reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – By 2035, U.S. cardiothoracic surgeons will see a 61% increase in the national caseload, and potentially a 121% increase in cases for each surgeon, according to a data analysis presented at the annual meeting of the American Association for Thoracic Surgery.

Using data from the American Board of Thoracic Surgery, a research team at Ohio State University performed case load calculations for 2035 based on cases per surgeon per year in 2010. The researchers estimated that the average caseload per surgeon in 2035 will be 299 cases, compared with a 2010 caseload of 135 per surgeon. This increase is not matched by the number of surgeons currently trained and certified annually.

Dr. John Ikonomidis, chief of the division of cardiothoracic surgery at the Medical University of South Carolina in Charleston, and a discussant on the presentation, said surgeon retirements and an increase in the population needing treatment have put the specialty in a bind.

“We have a bit of a crisis now, honestly, but this particular paper puts it in even further perspective,” Dr. Ikonomidis said in a video interview. “By 2035 we’re looking at a 3,000-surgeon shortage, relative to what would be available.” He noted that approximately 90 medical residents per year are certified as cardiothoracic surgeons, a rate which will not produce enough CT surgeons to meet the projected shortage.

“We need to continue to have this conversation,” he concluded. “It is a reminder that the predictions we made 15 years ago appear to be true, and we probably need to do something about it, at least in the short term.”

Dr. Ikonomidis reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – By 2035, U.S. cardiothoracic surgeons will see a 61% increase in the national caseload, and potentially a 121% increase in cases for each surgeon, according to a data analysis presented at the annual meeting of the American Association for Thoracic Surgery.

Using data from the American Board of Thoracic Surgery, a research team at Ohio State University performed case load calculations for 2035 based on cases per surgeon per year in 2010. The researchers estimated that the average caseload per surgeon in 2035 will be 299 cases, compared with a 2010 caseload of 135 per surgeon. This increase is not matched by the number of surgeons currently trained and certified annually.

Dr. John Ikonomidis, chief of the division of cardiothoracic surgery at the Medical University of South Carolina in Charleston, and a discussant on the presentation, said surgeon retirements and an increase in the population needing treatment have put the specialty in a bind.

“We have a bit of a crisis now, honestly, but this particular paper puts it in even further perspective,” Dr. Ikonomidis said in a video interview. “By 2035 we’re looking at a 3,000-surgeon shortage, relative to what would be available.” He noted that approximately 90 medical residents per year are certified as cardiothoracic surgeons, a rate which will not produce enough CT surgeons to meet the projected shortage.

“We need to continue to have this conversation,” he concluded. “It is a reminder that the predictions we made 15 years ago appear to be true, and we probably need to do something about it, at least in the short term.”

Dr. Ikonomidis reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

Although multiple surveys have been published regarding patient gender preference when choosing an ObGyn, overall results have not been analyzed. To address this literature gap, Kyle J. Tobler, MD, and colleagues at the Womack Army Medical Center in Fort Bragg, North Carolina, and Uniformed Services University of the Health Sciences in Bethesda, Maryland, searched multiple sources to provide a conglomerate analysis of patients’ gender preference when choosing an ObGyn. An abstract describing their study was published in Obstetrics & Gynecology in May 2016 and presented at the American College of Obstetricians and Gynecologists 2016 Annual Clinical and Scientific Meeting May 14−17, in Washington, DC.

A personal impetus for studying gender preference
The impetus for this project truly was initiated for Dr. Tobler when he was a 4th-year medical student. “I was trying to decide if Obstetrics and Gynecology was the right field for me,” he said. “I was discouraged by many people around me, who told me that men in ObGyn would not have a place, as female patients only wanted female ObGyns. And with the residency match at 60% to 70% women for ObGyn, it did seem that men would not have a place. Thus, I began searching the literature to verify if the question for gender preference for their ObGyn provider had been evaluated previously, and I found mixed results.” After medical school Dr. Tobler pursued this current meta-analysis to address the conflicting results.

Details of the study
Dr. Tobler and his colleagues explored PubMed, Embase, PsycINFO (American Psychological Association’s medical literature database), Cumulative Index to Nursing and Allied Health Literature (EBSCO Health’s database), Scopus (Elsevier’s abstract and citation database of peer-reviewed literature), and references of relevant articles. Included were 4,822 electronically-identified citations of English-language studies, including surveys administered to patients that specifically asked for gender preference of their ObGyn provider.

The researchers found that 23 studies met their inclusion criteria, comprising 14,736 patients. Overall, 8.3% (95% confidence interval [CI], 0.08-0.09) of ObGyn patients reported a preference for a male provider, 50.2% (95% CI, 0.49-0.51) preferred a female provider, and 41.3% (95% CI, 0.40-0.42) reported no gender preference when choosing an ObGyn.

What about US patients?
A subanalysis of studies (n = 9,861) conducted in the United States from 1999 to 2008 (with the last search undertaken in April 2015) showed that 8.4% (95% CI, 0.08-0.09) preferred a male ObGyn, 53.2% (95% CI, 0.52-0.54) preferred a female ObGyn, and 38.5% (95% CI, 0.38-0.39) had no gender preference.

“We were surprised by the numbers,” comments Dr. Tobler. “The general trend demonstrated a mix between no preference or a preference for female providers, but not by a large margin.”

“We considered analyzing for age,” he said, “but most of the studies gave a mean or median age value and were widely distributed. We were able, however, to break our analysis down into regions where one would expect a very strong preference for female providers—the Middle East and Africa. But in fact results were not much different than for Western countries. Our results for this subanalysis of Middle Eastern countries and Nigeria (n = 1,951) demonstrated that 8.7% of women (95% CI, 4.1-13.3) preferred a male provider, 51.2% (95% CI, 17.2-85.1) preferred a female provider, and 46.9% (95% CI, 9.3-84.5) had no gender preference.”

Updated May 20, 2016.

Although multiple surveys have been published regarding patient gender preference when choosing an ObGyn, overall results have not been analyzed. To address this literature gap, Kyle J. Tobler, MD, and colleagues at the Womack Army Medical Center in Fort Bragg, North Carolina, and Uniformed Services University of the Health Sciences in Bethesda, Maryland, searched multiple sources to provide a conglomerate analysis of patients’ gender preference when choosing an ObGyn. An abstract describing their study was published in Obstetrics & Gynecology in May 2016 and presented at the American College of Obstetricians and Gynecologists 2016 Annual Clinical and Scientific Meeting May 14−17, in Washington, DC.

A personal impetus for studying gender preference
The impetus for this project truly was initiated for Dr. Tobler when he was a 4th-year medical student. “I was trying to decide if Obstetrics and Gynecology was the right field for me,” he said. “I was discouraged by many people around me, who told me that men in ObGyn would not have a place, as female patients only wanted female ObGyns. And with the residency match at 60% to 70% women for ObGyn, it did seem that men would not have a place. Thus, I began searching the literature to verify if the question for gender preference for their ObGyn provider had been evaluated previously, and I found mixed results.” After medical school Dr. Tobler pursued this current meta-analysis to address the conflicting results.

Details of the study
Dr. Tobler and his colleagues explored PubMed, Embase, PsycINFO (American Psychological Association’s medical literature database), Cumulative Index to Nursing and Allied Health Literature (EBSCO Health’s database), Scopus (Elsevier’s abstract and citation database of peer-reviewed literature), and references of relevant articles. Included were 4,822 electronically-identified citations of English-language studies, including surveys administered to patients that specifically asked for gender preference of their ObGyn provider.

The researchers found that 23 studies met their inclusion criteria, comprising 14,736 patients. Overall, 8.3% (95% confidence interval [CI], 0.08-0.09) of ObGyn patients reported a preference for a male provider, 50.2% (95% CI, 0.49-0.51) preferred a female provider, and 41.3% (95% CI, 0.40-0.42) reported no gender preference when choosing an ObGyn.

What about US patients?
A subanalysis of studies (n = 9,861) conducted in the United States from 1999 to 2008 (with the last search undertaken in April 2015) showed that 8.4% (95% CI, 0.08-0.09) preferred a male ObGyn, 53.2% (95% CI, 0.52-0.54) preferred a female ObGyn, and 38.5% (95% CI, 0.38-0.39) had no gender preference.

“We were surprised by the numbers,” comments Dr. Tobler. “The general trend demonstrated a mix between no preference or a preference for female providers, but not by a large margin.”

“We considered analyzing for age,” he said, “but most of the studies gave a mean or median age value and were widely distributed. We were able, however, to break our analysis down into regions where one would expect a very strong preference for female providers—the Middle East and Africa. But in fact results were not much different than for Western countries. Our results for this subanalysis of Middle Eastern countries and Nigeria (n = 1,951) demonstrated that 8.7% of women (95% CI, 4.1-13.3) preferred a male provider, 51.2% (95% CI, 17.2-85.1) preferred a female provider, and 46.9% (95% CI, 9.3-84.5) had no gender preference.”

Updated May 20, 2016.

Although multiple surveys have been published regarding patient gender preference when choosing an ObGyn, overall results have not been analyzed. To address this literature gap, Kyle J. Tobler, MD, and colleagues at the Womack Army Medical Center in Fort Bragg, North Carolina, and Uniformed Services University of the Health Sciences in Bethesda, Maryland, searched multiple sources to provide a conglomerate analysis of patients’ gender preference when choosing an ObGyn. An abstract describing their study was published in Obstetrics & Gynecology in May 2016 and presented at the American College of Obstetricians and Gynecologists 2016 Annual Clinical and Scientific Meeting May 14−17, in Washington, DC.

A personal impetus for studying gender preference
The impetus for this project truly was initiated for Dr. Tobler when he was a 4th-year medical student. “I was trying to decide if Obstetrics and Gynecology was the right field for me,” he said. “I was discouraged by many people around me, who told me that men in ObGyn would not have a place, as female patients only wanted female ObGyns. And with the residency match at 60% to 70% women for ObGyn, it did seem that men would not have a place. Thus, I began searching the literature to verify if the question for gender preference for their ObGyn provider had been evaluated previously, and I found mixed results.” After medical school Dr. Tobler pursued this current meta-analysis to address the conflicting results.

Details of the study
Dr. Tobler and his colleagues explored PubMed, Embase, PsycINFO (American Psychological Association’s medical literature database), Cumulative Index to Nursing and Allied Health Literature (EBSCO Health’s database), Scopus (Elsevier’s abstract and citation database of peer-reviewed literature), and references of relevant articles. Included were 4,822 electronically-identified citations of English-language studies, including surveys administered to patients that specifically asked for gender preference of their ObGyn provider.

The researchers found that 23 studies met their inclusion criteria, comprising 14,736 patients. Overall, 8.3% (95% confidence interval [CI], 0.08-0.09) of ObGyn patients reported a preference for a male provider, 50.2% (95% CI, 0.49-0.51) preferred a female provider, and 41.3% (95% CI, 0.40-0.42) reported no gender preference when choosing an ObGyn.

What about US patients?
A subanalysis of studies (n = 9,861) conducted in the United States from 1999 to 2008 (with the last search undertaken in April 2015) showed that 8.4% (95% CI, 0.08-0.09) preferred a male ObGyn, 53.2% (95% CI, 0.52-0.54) preferred a female ObGyn, and 38.5% (95% CI, 0.38-0.39) had no gender preference.

“We were surprised by the numbers,” comments Dr. Tobler. “The general trend demonstrated a mix between no preference or a preference for female providers, but not by a large margin.”

“We considered analyzing for age,” he said, “but most of the studies gave a mean or median age value and were widely distributed. We were able, however, to break our analysis down into regions where one would expect a very strong preference for female providers—the Middle East and Africa. But in fact results were not much different than for Western countries. Our results for this subanalysis of Middle Eastern countries and Nigeria (n = 1,951) demonstrated that 8.7% of women (95% CI, 4.1-13.3) preferred a male provider, 51.2% (95% CI, 17.2-85.1) preferred a female provider, and 46.9% (95% CI, 9.3-84.5) had no gender preference.”

Updated May 20, 2016.

BALTIMORE – Surgical resection of early-stage non–small cell lung cancer afforded a superior survival advantage for patients than stereotactic body radiation therapy (SBRT), according to a study presented at the 2016 annual meeting of the American Association for Thoracic Surgery.

While an increasing number of non–small cell lung cancer patients have been treated with SBRT, it appears that surgery may still be the better option. Analysis of both matched and unmatched patient groups found that SBRT was associated with significantly lower survival than wedge resection.

“Frankly, I was surprised to see such a big difference between SBRT and wedge resection,” said Dr. Walter Weder, professor of surgery at University Hospital Zürich, in an interview at AATS 2016. Dr Weder served as a discussant on the paper, and said the results confirm that surgeons should be involved in discussions with patients when they are considering treatment options. “Surgery can be done safely... and patients should know this information.”

Dr. Weder reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – Surgical resection of early-stage non–small cell lung cancer afforded a superior survival advantage for patients than stereotactic body radiation therapy (SBRT), according to a study presented at the 2016 annual meeting of the American Association for Thoracic Surgery.

While an increasing number of non–small cell lung cancer patients have been treated with SBRT, it appears that surgery may still be the better option. Analysis of both matched and unmatched patient groups found that SBRT was associated with significantly lower survival than wedge resection.

“Frankly, I was surprised to see such a big difference between SBRT and wedge resection,” said Dr. Walter Weder, professor of surgery at University Hospital Zürich, in an interview at AATS 2016. Dr Weder served as a discussant on the paper, and said the results confirm that surgeons should be involved in discussions with patients when they are considering treatment options. “Surgery can be done safely... and patients should know this information.”

Dr. Weder reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – Surgical resection of early-stage non–small cell lung cancer afforded a superior survival advantage for patients than stereotactic body radiation therapy (SBRT), according to a study presented at the 2016 annual meeting of the American Association for Thoracic Surgery.

While an increasing number of non–small cell lung cancer patients have been treated with SBRT, it appears that surgery may still be the better option. Analysis of both matched and unmatched patient groups found that SBRT was associated with significantly lower survival than wedge resection.

“Frankly, I was surprised to see such a big difference between SBRT and wedge resection,” said Dr. Walter Weder, professor of surgery at University Hospital Zürich, in an interview at AATS 2016. Dr Weder served as a discussant on the paper, and said the results confirm that surgeons should be involved in discussions with patients when they are considering treatment options. “Surgery can be done safely... and patients should know this information.”

Dr. Weder reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

Micrograph showing ALL

Patients with high-risk, relapsed/refractory acute lymphoblastic leukemia (ALL) may be sensitive to treatment with SMAC mimetics, according to researchers.

One SMAC mimetic in particular, birinapant, demonstrated varied activity in samples from ALL patients, but samples from patients with resistant disease were the most sensitive to the drug.

Birinapant also had “marked antileukemic effects” in some mice with ALL.

The researchers found this antileukemic activity was dependent on simultaneous activation of apoptosis and necroptosis.

The team reported these findings in Science Translational Medicine.

“Our research reveals that an alternative cell-death program, necroptosis, can be activated in human ALL cells,” said study author Beat Bornhauser, PhD, of the Children’s Hospital Zurich in Switzerland.

“This enables leukemia cells that barely respond to existing chemotherapeutic drugs to be killed off.”

In vitro and in vivo activity

The researchers tested the efficacy of SMAC mimetics in a set of 51 patient-derived B-cell precursor ALL xenografts, which was enriched for samples from relapsed and drug-resistant disease.

The response to birinapant varied greatly, but samples from high-risk or relapsed patients tended to be highly sensitive to the drug.

The researchers observed similar response profiles with the SMAC mimetic LCL161, although this drug proved less potent than birinapant.

The team also evaluated the antileukemic activity of SMAC mimetics in mouse models of ALL.

Birinapant delayed disease progression and induced complete responses in sensitive ALL cases. LCL161, on the other hand, did not display any in vivo activity.

Determining the mechanism of activity

The researchers used CRISPR-Cas9 to determine how SMAC mimetics fight ALL, and they discovered that the drugs trigger both apoptosis and necroptosis.

If the genes responsible for apoptosis were disabled via genome editing, leukemia cells died due to necroptosis after SMAC mimetics had been administered. If necroptotic genes were disabled, apoptosis led to cell death.

Only the simultaneous deactivation of apoptotic and necroptotic genes resulted in the complete resistance of leukemic cells to SMAC mimetics.

Therefore, the researchers concluded that simultaneous activation of apoptosis and necroptosis is responsible for the strong anti-leukemic effect of SMAC mimetics.

“SMAC mimetics have great potential to eliminate leukemia cells in patients that aren’t sensitive to established chemotherapeutic drugs,” Dr Bornhauser said. “They are effectively a double-edged sword. They kill cells that block apoptosis through necroptosis.”

The researchers are now looking for suitable biomarkers to identify patients who might benefit from treatment with SMAC mimetics in clinical trials.

Micrograph showing ALL

Patients with high-risk, relapsed/refractory acute lymphoblastic leukemia (ALL) may be sensitive to treatment with SMAC mimetics, according to researchers.

One SMAC mimetic in particular, birinapant, demonstrated varied activity in samples from ALL patients, but samples from patients with resistant disease were the most sensitive to the drug.

Birinapant also had “marked antileukemic effects” in some mice with ALL.

The researchers found this antileukemic activity was dependent on simultaneous activation of apoptosis and necroptosis.

The team reported these findings in Science Translational Medicine.

“Our research reveals that an alternative cell-death program, necroptosis, can be activated in human ALL cells,” said study author Beat Bornhauser, PhD, of the Children’s Hospital Zurich in Switzerland.

“This enables leukemia cells that barely respond to existing chemotherapeutic drugs to be killed off.”

In vitro and in vivo activity

The researchers tested the efficacy of SMAC mimetics in a set of 51 patient-derived B-cell precursor ALL xenografts, which was enriched for samples from relapsed and drug-resistant disease.

The response to birinapant varied greatly, but samples from high-risk or relapsed patients tended to be highly sensitive to the drug.

The researchers observed similar response profiles with the SMAC mimetic LCL161, although this drug proved less potent than birinapant.

The team also evaluated the antileukemic activity of SMAC mimetics in mouse models of ALL.

Birinapant delayed disease progression and induced complete responses in sensitive ALL cases. LCL161, on the other hand, did not display any in vivo activity.

Determining the mechanism of activity

The researchers used CRISPR-Cas9 to determine how SMAC mimetics fight ALL, and they discovered that the drugs trigger both apoptosis and necroptosis.

If the genes responsible for apoptosis were disabled via genome editing, leukemia cells died due to necroptosis after SMAC mimetics had been administered. If necroptotic genes were disabled, apoptosis led to cell death.

Only the simultaneous deactivation of apoptotic and necroptotic genes resulted in the complete resistance of leukemic cells to SMAC mimetics.

Therefore, the researchers concluded that simultaneous activation of apoptosis and necroptosis is responsible for the strong anti-leukemic effect of SMAC mimetics.

“SMAC mimetics have great potential to eliminate leukemia cells in patients that aren’t sensitive to established chemotherapeutic drugs,” Dr Bornhauser said. “They are effectively a double-edged sword. They kill cells that block apoptosis through necroptosis.”

The researchers are now looking for suitable biomarkers to identify patients who might benefit from treatment with SMAC mimetics in clinical trials.

Micrograph showing ALL

Patients with high-risk, relapsed/refractory acute lymphoblastic leukemia (ALL) may be sensitive to treatment with SMAC mimetics, according to researchers.

One SMAC mimetic in particular, birinapant, demonstrated varied activity in samples from ALL patients, but samples from patients with resistant disease were the most sensitive to the drug.

Birinapant also had “marked antileukemic effects” in some mice with ALL.

The researchers found this antileukemic activity was dependent on simultaneous activation of apoptosis and necroptosis.

The team reported these findings in Science Translational Medicine.

“Our research reveals that an alternative cell-death program, necroptosis, can be activated in human ALL cells,” said study author Beat Bornhauser, PhD, of the Children’s Hospital Zurich in Switzerland.

“This enables leukemia cells that barely respond to existing chemotherapeutic drugs to be killed off.”

In vitro and in vivo activity

The researchers tested the efficacy of SMAC mimetics in a set of 51 patient-derived B-cell precursor ALL xenografts, which was enriched for samples from relapsed and drug-resistant disease.

The response to birinapant varied greatly, but samples from high-risk or relapsed patients tended to be highly sensitive to the drug.

The researchers observed similar response profiles with the SMAC mimetic LCL161, although this drug proved less potent than birinapant.

The team also evaluated the antileukemic activity of SMAC mimetics in mouse models of ALL.

Birinapant delayed disease progression and induced complete responses in sensitive ALL cases. LCL161, on the other hand, did not display any in vivo activity.

Determining the mechanism of activity

The researchers used CRISPR-Cas9 to determine how SMAC mimetics fight ALL, and they discovered that the drugs trigger both apoptosis and necroptosis.

If the genes responsible for apoptosis were disabled via genome editing, leukemia cells died due to necroptosis after SMAC mimetics had been administered. If necroptotic genes were disabled, apoptosis led to cell death.

Only the simultaneous deactivation of apoptotic and necroptotic genes resulted in the complete resistance of leukemic cells to SMAC mimetics.

Therefore, the researchers concluded that simultaneous activation of apoptosis and necroptosis is responsible for the strong anti-leukemic effect of SMAC mimetics.

“SMAC mimetics have great potential to eliminate leukemia cells in patients that aren’t sensitive to established chemotherapeutic drugs,” Dr Bornhauser said. “They are effectively a double-edged sword. They kill cells that block apoptosis through necroptosis.”

The researchers are now looking for suitable biomarkers to identify patients who might benefit from treatment with SMAC mimetics in clinical trials.

Transplant preparation

Photo by Chad McNeeley

CHICAGO—An interim analysis of a large, phase 3 study has confirmed that upfront autologous stem cell transplantation (ASCT) is still the preferred

treatment for newly diagnosed, young multiple myeloma (MM) patients, even in the age of novel agents such as bortezomib.

Investigators compared 4 cycles of bortezomib-melphalan-prednisone (VMP) with high-dose melphalan (HDM) and single or double ASCT, depending upon the policy of the treating institution.

At a median follow-up of 24 months, the 3-year progression-free survival (PFS) was significantly better for patients who had received ASCT.

Michele Cavo, MD, of Seràgnoli Institute of Hematology in Bologna, Italy, reported the results of this first interim analysis of the European Myeloma Network trial (EMN/HO95 MM) at a press briefing preceding the 2016 ASCO Annual Meeting. More details will be presented at the meeting itself (abstract 8000).

Study investigators enrolled 1503 patients from February 2011 through April 2014. They performed the specified interim analysis in January 2016.

Patients were 65 years or younger, and all received bortezomib-based induction therapy followed by stem cell collection. Investigators then randomized 1266 patients to receive either VMP (n=754) or HDM plus single or double ASCT (n=512).

Patients underwent a second randomization to either 2 cycles of bortezomib-based consolidation or no consolidation therapy.

All patients received lenalidomide maintenance until disease progression. The primary endpoint was PFS after the first randomization.

Results

PFS was significantly longer in patients who had received a transplant, with a hazard ratio (HR) of 0.76, 95% confidence interval (CI) of 0.61-0.94, and P value of 0.01.

This benefit held true for patients with revised ISS stage III (HR=0.52, 95% CI 0.32-0.84, P=0.01).

And patients with high-risk cytogenetics also retained the benefit (HR=0.72, 95% CI 0.54-0.97, P=0.03). High-risk was defined as t(4;14), del(17p), del(1p), or gain of 1q.

Investigators also performed a multivariate analysis and found randomization to the HDM arm to be an independent predictor of prolonged PFS (HR=0.61, 95% CI 0.45-0.82, P=0.001).

There was no significant difference between the 2 arms in terms of stringent complete response and complete response.

However, when very good partial response was included in the best-response analysis, patients in the transplant arm fared significantly better (P<0.0001) than patients in the VMP arm—84% and 74%, respectively.

Investigators have not yet completed the interim data analysis related to the second randomization. The study is ongoing, and future analyses will include overall survival, toxicity, quality of life, and other measures.

This study was funded by the Haemato Oncology Foundation for Adults in the Netherlands (HOVON).

Transplant preparation

Photo by Chad McNeeley

CHICAGO—An interim analysis of a large, phase 3 study has confirmed that upfront autologous stem cell transplantation (ASCT) is still the preferred

treatment for newly diagnosed, young multiple myeloma (MM) patients, even in the age of novel agents such as bortezomib.

Investigators compared 4 cycles of bortezomib-melphalan-prednisone (VMP) with high-dose melphalan (HDM) and single or double ASCT, depending upon the policy of the treating institution.

At a median follow-up of 24 months, the 3-year progression-free survival (PFS) was significantly better for patients who had received ASCT.

Michele Cavo, MD, of Seràgnoli Institute of Hematology in Bologna, Italy, reported the results of this first interim analysis of the European Myeloma Network trial (EMN/HO95 MM) at a press briefing preceding the 2016 ASCO Annual Meeting. More details will be presented at the meeting itself (abstract 8000).

Study investigators enrolled 1503 patients from February 2011 through April 2014. They performed the specified interim analysis in January 2016.

Patients were 65 years or younger, and all received bortezomib-based induction therapy followed by stem cell collection. Investigators then randomized 1266 patients to receive either VMP (n=754) or HDM plus single or double ASCT (n=512).

Patients underwent a second randomization to either 2 cycles of bortezomib-based consolidation or no consolidation therapy.

All patients received lenalidomide maintenance until disease progression. The primary endpoint was PFS after the first randomization.

Results

PFS was significantly longer in patients who had received a transplant, with a hazard ratio (HR) of 0.76, 95% confidence interval (CI) of 0.61-0.94, and P value of 0.01.

This benefit held true for patients with revised ISS stage III (HR=0.52, 95% CI 0.32-0.84, P=0.01).

And patients with high-risk cytogenetics also retained the benefit (HR=0.72, 95% CI 0.54-0.97, P=0.03). High-risk was defined as t(4;14), del(17p), del(1p), or gain of 1q.

Investigators also performed a multivariate analysis and found randomization to the HDM arm to be an independent predictor of prolonged PFS (HR=0.61, 95% CI 0.45-0.82, P=0.001).

There was no significant difference between the 2 arms in terms of stringent complete response and complete response.

However, when very good partial response was included in the best-response analysis, patients in the transplant arm fared significantly better (P<0.0001) than patients in the VMP arm—84% and 74%, respectively.

Investigators have not yet completed the interim data analysis related to the second randomization. The study is ongoing, and future analyses will include overall survival, toxicity, quality of life, and other measures.

This study was funded by the Haemato Oncology Foundation for Adults in the Netherlands (HOVON).

Transplant preparation

Photo by Chad McNeeley

CHICAGO—An interim analysis of a large, phase 3 study has confirmed that upfront autologous stem cell transplantation (ASCT) is still the preferred

treatment for newly diagnosed, young multiple myeloma (MM) patients, even in the age of novel agents such as bortezomib.

Investigators compared 4 cycles of bortezomib-melphalan-prednisone (VMP) with high-dose melphalan (HDM) and single or double ASCT, depending upon the policy of the treating institution.

At a median follow-up of 24 months, the 3-year progression-free survival (PFS) was significantly better for patients who had received ASCT.

Michele Cavo, MD, of Seràgnoli Institute of Hematology in Bologna, Italy, reported the results of this first interim analysis of the European Myeloma Network trial (EMN/HO95 MM) at a press briefing preceding the 2016 ASCO Annual Meeting. More details will be presented at the meeting itself (abstract 8000).

Study investigators enrolled 1503 patients from February 2011 through April 2014. They performed the specified interim analysis in January 2016.

Patients were 65 years or younger, and all received bortezomib-based induction therapy followed by stem cell collection. Investigators then randomized 1266 patients to receive either VMP (n=754) or HDM plus single or double ASCT (n=512).

Patients underwent a second randomization to either 2 cycles of bortezomib-based consolidation or no consolidation therapy.

All patients received lenalidomide maintenance until disease progression. The primary endpoint was PFS after the first randomization.

Results

PFS was significantly longer in patients who had received a transplant, with a hazard ratio (HR) of 0.76, 95% confidence interval (CI) of 0.61-0.94, and P value of 0.01.

This benefit held true for patients with revised ISS stage III (HR=0.52, 95% CI 0.32-0.84, P=0.01).

And patients with high-risk cytogenetics also retained the benefit (HR=0.72, 95% CI 0.54-0.97, P=0.03). High-risk was defined as t(4;14), del(17p), del(1p), or gain of 1q.

Investigators also performed a multivariate analysis and found randomization to the HDM arm to be an independent predictor of prolonged PFS (HR=0.61, 95% CI 0.45-0.82, P=0.001).

There was no significant difference between the 2 arms in terms of stringent complete response and complete response.

However, when very good partial response was included in the best-response analysis, patients in the transplant arm fared significantly better (P<0.0001) than patients in the VMP arm—84% and 74%, respectively.

Investigators have not yet completed the interim data analysis related to the second randomization. The study is ongoing, and future analyses will include overall survival, toxicity, quality of life, and other measures.

This study was funded by the Haemato Oncology Foundation for Adults in the Netherlands (HOVON).

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

SAN FRANCISCO—A new study has shown that hydroxyurea (HU) can improve lung function in young patients with sickle cell disease (SCD).

“Persons with sickle cell disease experience an annual decline in lung function that starts in childhood,” said study investigator Anya McLaren, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada.

“This study is the first of its kind to look at the effect of hydroxyurea on lung function. We found that hydroxyurea improves annual pulmonary function decline in children with sickle cell disease by more than one-third.”

The study was presented at the ATS 2016 International Conference as abstract 7225.

For this study, Dr McLaren and her colleagues evaluated the effects of HU in 94 SCD patients. The patients’ average age at baseline was 11 (range, 6 to 20), 96% of patients had HbSS genotype, and 47% were male.

The patients were followed for 4 years after HU initiation. The investigators assessed lung function before and after HU initiation in a few ways.

They used the forced expiratory volume (FEV) test, which measures how much air a person can exhale during a forced breath. The amount of air can be measured during the first second of the forced breath (FEV1) and at later time points.

Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. If the FEV1/FVC ratio is less than 80%, it indicates that an obstructive defect is present.

The investigators also assessed FEF25-75, or the forced expiratory flow at 25%–75% of FVC. This measurement helps determine if there is an obstruction in the airway.

In addition, the team measured total lung capacity.

Results

The investigators found no significant change in total lung capacity, FVC, or FEV1/FVC predicted measurements after patients began receiving HU.

However, there were significant improvements in both FEV1 and FEF25-75 after treatment.

The annual rate of decline in predicted FEV1 and FEF25-75 before patients started HU was -1.98%/year (95% CI -2.57 to -1.39) and -3.59%/year (95% CI -4.43 to -2.75), respectively.

After HU treatment began, there was a significant (P<0.05) improvement in the annual decline, to -1.28%/year (95% CI -1.79 to -0.76) and -2.88%/year (95% CI -3.49 to -2.28), respectively.

The investigators noted that changes in FEV1 and FEF25-75 were independent of a patient’s age at baseline and the time from HU therapy initiation.

Dr McLaren pointed out that HU is underused in SCD patients, likely because clinicians are concerned about patient non-compliance and afraid of potential side effects, particularly carcinogenesis. But some of those fears may be unfounded, she said.

“Long-term observational studies suggest beneficial effects [of HU] without excessive damage to bone marrow, deleterious effects on growth and development, altered fertility, accumulation of mutations, or increased carcinogenicity,” Dr McLaren said.

“Evidence that lung function may be better preserved while on hydroxyurea may encourage compliance and adherence to this medication for patients with sickle cell disease. In combination with the established safety data, it hopefully will promote physician recommendations for hydroxyurea initiation and encouragement of compliance.”

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

SAN FRANCISCO—A new study has shown that hydroxyurea (HU) can improve lung function in young patients with sickle cell disease (SCD).

“Persons with sickle cell disease experience an annual decline in lung function that starts in childhood,” said study investigator Anya McLaren, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada.

“This study is the first of its kind to look at the effect of hydroxyurea on lung function. We found that hydroxyurea improves annual pulmonary function decline in children with sickle cell disease by more than one-third.”

The study was presented at the ATS 2016 International Conference as abstract 7225.

For this study, Dr McLaren and her colleagues evaluated the effects of HU in 94 SCD patients. The patients’ average age at baseline was 11 (range, 6 to 20), 96% of patients had HbSS genotype, and 47% were male.

The patients were followed for 4 years after HU initiation. The investigators assessed lung function before and after HU initiation in a few ways.

They used the forced expiratory volume (FEV) test, which measures how much air a person can exhale during a forced breath. The amount of air can be measured during the first second of the forced breath (FEV1) and at later time points.

Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. If the FEV1/FVC ratio is less than 80%, it indicates that an obstructive defect is present.

The investigators also assessed FEF25-75, or the forced expiratory flow at 25%–75% of FVC. This measurement helps determine if there is an obstruction in the airway.

In addition, the team measured total lung capacity.

Results

The investigators found no significant change in total lung capacity, FVC, or FEV1/FVC predicted measurements after patients began receiving HU.

However, there were significant improvements in both FEV1 and FEF25-75 after treatment.

The annual rate of decline in predicted FEV1 and FEF25-75 before patients started HU was -1.98%/year (95% CI -2.57 to -1.39) and -3.59%/year (95% CI -4.43 to -2.75), respectively.

After HU treatment began, there was a significant (P<0.05) improvement in the annual decline, to -1.28%/year (95% CI -1.79 to -0.76) and -2.88%/year (95% CI -3.49 to -2.28), respectively.

The investigators noted that changes in FEV1 and FEF25-75 were independent of a patient’s age at baseline and the time from HU therapy initiation.

Dr McLaren pointed out that HU is underused in SCD patients, likely because clinicians are concerned about patient non-compliance and afraid of potential side effects, particularly carcinogenesis. But some of those fears may be unfounded, she said.

“Long-term observational studies suggest beneficial effects [of HU] without excessive damage to bone marrow, deleterious effects on growth and development, altered fertility, accumulation of mutations, or increased carcinogenicity,” Dr McLaren said.

“Evidence that lung function may be better preserved while on hydroxyurea may encourage compliance and adherence to this medication for patients with sickle cell disease. In combination with the established safety data, it hopefully will promote physician recommendations for hydroxyurea initiation and encouragement of compliance.”

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

SAN FRANCISCO—A new study has shown that hydroxyurea (HU) can improve lung function in young patients with sickle cell disease (SCD).

“Persons with sickle cell disease experience an annual decline in lung function that starts in childhood,” said study investigator Anya McLaren, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada.

“This study is the first of its kind to look at the effect of hydroxyurea on lung function. We found that hydroxyurea improves annual pulmonary function decline in children with sickle cell disease by more than one-third.”

The study was presented at the ATS 2016 International Conference as abstract 7225.

For this study, Dr McLaren and her colleagues evaluated the effects of HU in 94 SCD patients. The patients’ average age at baseline was 11 (range, 6 to 20), 96% of patients had HbSS genotype, and 47% were male.

The patients were followed for 4 years after HU initiation. The investigators assessed lung function before and after HU initiation in a few ways.

They used the forced expiratory volume (FEV) test, which measures how much air a person can exhale during a forced breath. The amount of air can be measured during the first second of the forced breath (FEV1) and at later time points.

Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. If the FEV1/FVC ratio is less than 80%, it indicates that an obstructive defect is present.

The investigators also assessed FEF25-75, or the forced expiratory flow at 25%–75% of FVC. This measurement helps determine if there is an obstruction in the airway.

In addition, the team measured total lung capacity.

Results

The investigators found no significant change in total lung capacity, FVC, or FEV1/FVC predicted measurements after patients began receiving HU.

However, there were significant improvements in both FEV1 and FEF25-75 after treatment.

The annual rate of decline in predicted FEV1 and FEF25-75 before patients started HU was -1.98%/year (95% CI -2.57 to -1.39) and -3.59%/year (95% CI -4.43 to -2.75), respectively.

After HU treatment began, there was a significant (P<0.05) improvement in the annual decline, to -1.28%/year (95% CI -1.79 to -0.76) and -2.88%/year (95% CI -3.49 to -2.28), respectively.

The investigators noted that changes in FEV1 and FEF25-75 were independent of a patient’s age at baseline and the time from HU therapy initiation.

Dr McLaren pointed out that HU is underused in SCD patients, likely because clinicians are concerned about patient non-compliance and afraid of potential side effects, particularly carcinogenesis. But some of those fears may be unfounded, she said.

“Long-term observational studies suggest beneficial effects [of HU] without excessive damage to bone marrow, deleterious effects on growth and development, altered fertility, accumulation of mutations, or increased carcinogenicity,” Dr McLaren said.

“Evidence that lung function may be better preserved while on hydroxyurea may encourage compliance and adherence to this medication for patients with sickle cell disease. In combination with the established safety data, it hopefully will promote physician recommendations for hydroxyurea initiation and encouragement of compliance.”

Hematopoietic stem cells

in the bone marrow

Scientists believe they have come one step closer to creating hematopoietic stem cells (HSCs) that are just like the real thing.

“Our work focuses on finding a way to generate a supply of these life-saving hematopoietic stem cells in the lab so that they are a perfect match to the patient in need of a transplant,” said Hanna Mikkola, MD, PhD, of the University of California, Los Angeles.

“One big challenge is that when we try to create hematopoietic stem cells from pluripotent stem cells in the lab, they don’t acquire the same abilities of the real hematopoietic stem cells found in the body.”

Dr Mikkola and her colleagues described their attempts to overcome this challenge in Nature Cell Biology.

The researchers tried to create HSCs from pluripotent stem cells, but when they compared the lab-created cells to HSCs found in the body, they found that HOXA genes weren’t activated in the lab-created cells.

The team also discovered that HOXA genes help HSCs maintain their stem-cell attributes, such as the ability to self-renew.

“Without the ability to self-renew, hematopoietic stem cells cannot be used for transplantation therapies,” said Vincenzo Calvanese, PhD, an assistant project scientist in Dr Mikkola’s lab.

“Our findings show that the activation of HOXA genes can be used as a marker for hematopoietic stem cells that have acquired the capacity to renew themselves.”

The researchers’ next challenge was to pinpoint the naturally occurring process that activates HOXA genes so they could try to replicate the process in the lab.

They found that mimicking the effects of retinoic acid acts like a switch that turns on the HOXA genes during HSC development.

“Inducing retinoic acid activity at a very specific time in cell development makes our lab-created cells more similar to the real hematopoietic stem cells found in the body,” said Diana Dou, a graduate student in Dr Mikkola’s lab.

“This is an important step forward as we work to develop hematopoietic stem cells for transplantation therapies for life-threatening blood diseases.”

The researchers’ next step will be to refine the process they’ve developed in order to produce lab-created HSCs that have—and maintain—all the functions of human HSCs.

Hematopoietic stem cells

in the bone marrow

Scientists believe they have come one step closer to creating hematopoietic stem cells (HSCs) that are just like the real thing.

“Our work focuses on finding a way to generate a supply of these life-saving hematopoietic stem cells in the lab so that they are a perfect match to the patient in need of a transplant,” said Hanna Mikkola, MD, PhD, of the University of California, Los Angeles.

“One big challenge is that when we try to create hematopoietic stem cells from pluripotent stem cells in the lab, they don’t acquire the same abilities of the real hematopoietic stem cells found in the body.”

Dr Mikkola and her colleagues described their attempts to overcome this challenge in Nature Cell Biology.

The researchers tried to create HSCs from pluripotent stem cells, but when they compared the lab-created cells to HSCs found in the body, they found that HOXA genes weren’t activated in the lab-created cells.

The team also discovered that HOXA genes help HSCs maintain their stem-cell attributes, such as the ability to self-renew.

“Without the ability to self-renew, hematopoietic stem cells cannot be used for transplantation therapies,” said Vincenzo Calvanese, PhD, an assistant project scientist in Dr Mikkola’s lab.

“Our findings show that the activation of HOXA genes can be used as a marker for hematopoietic stem cells that have acquired the capacity to renew themselves.”

The researchers’ next challenge was to pinpoint the naturally occurring process that activates HOXA genes so they could try to replicate the process in the lab.

They found that mimicking the effects of retinoic acid acts like a switch that turns on the HOXA genes during HSC development.

“Inducing retinoic acid activity at a very specific time in cell development makes our lab-created cells more similar to the real hematopoietic stem cells found in the body,” said Diana Dou, a graduate student in Dr Mikkola’s lab.

“This is an important step forward as we work to develop hematopoietic stem cells for transplantation therapies for life-threatening blood diseases.”

The researchers’ next step will be to refine the process they’ve developed in order to produce lab-created HSCs that have—and maintain—all the functions of human HSCs.

Hematopoietic stem cells

in the bone marrow

Scientists believe they have come one step closer to creating hematopoietic stem cells (HSCs) that are just like the real thing.

“Our work focuses on finding a way to generate a supply of these life-saving hematopoietic stem cells in the lab so that they are a perfect match to the patient in need of a transplant,” said Hanna Mikkola, MD, PhD, of the University of California, Los Angeles.

“One big challenge is that when we try to create hematopoietic stem cells from pluripotent stem cells in the lab, they don’t acquire the same abilities of the real hematopoietic stem cells found in the body.”

Dr Mikkola and her colleagues described their attempts to overcome this challenge in Nature Cell Biology.

The researchers tried to create HSCs from pluripotent stem cells, but when they compared the lab-created cells to HSCs found in the body, they found that HOXA genes weren’t activated in the lab-created cells.

The team also discovered that HOXA genes help HSCs maintain their stem-cell attributes, such as the ability to self-renew.

“Without the ability to self-renew, hematopoietic stem cells cannot be used for transplantation therapies,” said Vincenzo Calvanese, PhD, an assistant project scientist in Dr Mikkola’s lab.

“Our findings show that the activation of HOXA genes can be used as a marker for hematopoietic stem cells that have acquired the capacity to renew themselves.”

The researchers’ next challenge was to pinpoint the naturally occurring process that activates HOXA genes so they could try to replicate the process in the lab.

They found that mimicking the effects of retinoic acid acts like a switch that turns on the HOXA genes during HSC development.

“Inducing retinoic acid activity at a very specific time in cell development makes our lab-created cells more similar to the real hematopoietic stem cells found in the body,” said Diana Dou, a graduate student in Dr Mikkola’s lab.

“This is an important step forward as we work to develop hematopoietic stem cells for transplantation therapies for life-threatening blood diseases.”

The researchers’ next step will be to refine the process they’ve developed in order to produce lab-created HSCs that have—and maintain—all the functions of human HSCs.

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.

“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.

“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.

Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.

Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.

At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.

Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.

“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.

“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.

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On Twitter @JessCraig_OP

Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.

“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.

“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.

Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.

Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.

At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.

Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.

“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.

“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.

[email protected]

On Twitter @JessCraig_OP

Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.

“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.

“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.

Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.

Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.

At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.

Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.

“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.

“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.

[email protected]

On Twitter @JessCraig_OP