From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

From left to right: Brandon

Aubrey, Gemma Kelly,

and Marco Herold

Photo courtesy of the

Walter and Eliza Hall Institute

The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.

Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.

These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.

“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.

After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.

So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.

The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice.  Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.

“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.

“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Warfarin tablets

An analysis of data from the ENGAGE AF-TIMI 48 trial has shown that patients with a genetic sensitivity to warfarin had higher rates of bleeding during the first several months of treatment and benefitted from treatment with a different anticoagulant.

The research, published in The Lancet, suggests that using genetic analyses to identify patients who are most at risk of bleeding with warfarin could offer safety benefits, particularly in the first 90 days of treatment.

“We were able to look at patients from around the world who were being treated with warfarin and found that certain genetic variants make a difference for an individual’s risk for bleeding,” said study author Jessica L. Mega, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“For these patients who are sensitive or highly sensitive responders based on genetics, we observed a higher risk of bleeding in the first several months with warfarin, and consequently, a big reduction in bleeding when treated with the drug edoxaban instead of warfarin.”

The FDA label for warfarin notes that genetic variants in 2 genes—CYP2C9 and VKORC1—can assist in determining the right warfarin dosage. But a conclusive link between variation in these genes and bleeding has been debated.

By leveraging data from the ENGAGE AF-TIMI 48 trial—in which patients with atrial fibrillation received warfarin or 2 different doses of edoxaban—investigators were able to observe connections between genetic differences and patient outcomes.

A subgroup of patients was genotyped for variants in CYP2C9 and VKORC1, and the results were used to identify normal responders, sensitive responders, and highly sensitive responders to warfarin.

Dr Mega and her colleagues looked at data from 14,348 patients. Of the 4833 patients taking warfarin, 61.7% were normal responders, 35.4% were sensitive responders, and 9.2% were highly sensitive responders.

In the first 90 days of treatment, normal responders were over-anticoagulated a median of 2.2% of the time, compared to 8.4% of the time for sensitive responders, and 18.3% of the time for highly sensitive responders (P_trend<0.0001).

Both sensitive and highly sensitive responders also had an increased risk of bleeding in the first 90 days when compared to normal responders. The hazard ratios were 1.31 for sensitive responders (P=0.0179) and 2.66 for highly sensitive responders (P<0.0001).

As a result, during the first 90 days, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders.

Compared with warfarin, both the higher and lower doses of edoxaban reduced bleeding more in sensitive and highly sensitive responders than in normal responders (P_interaction=0.0066 and 0.0036 for the higher and lower doses, respectively).

“These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, also of Brigham and Women’s Hospital.

The ENGAGE AF-TIMI 48 trial was supported by research grants from Daiichi Sankyo, makers of edoxaban.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Colony of iPSCs

Image by James Thompson

Induced pluripotent stem cells (iPSCs) may help elucidate the pathogenesis of bone marrow failure (BMF) in Fanconi anemia (FA), researchers say.

They generated iPSCs from FA patients and found evidence suggesting that hematopoietic consequences originate at the earliest hematopoietic stage.

Specifically, hemoangiogenic progenitor cells (HAPCs) from FA-iPSCs produced significantly fewer hematopoietic and endothelial cells than controls.

“Although various consequences in hematopoietic stem cells have been attributed to FA-BMF, its cause is still unknown,” said study author Megumu K. Saito, MD, PhD, of Kyoto University in Japan.

“To address the issue, our team established iPSCs from 2 FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal-type immature blood cells [KDR⁺ CD34⁺ HAPCs] from these iPSCs.”

The researchers assessed differentiation in the FA-iPSC-derived HAPCs (FA-HAPCs) and found they produced significantly fewer CD34⁺ CD45⁺ hematopoietic precursors—and later, myeloid and erythroid lineage hematopoietic cells—than control cells. Likewise, FA-HAPCs produced fewer CD31⁺ endothelial cells than controls.

Cell cycle distribution in FA-HAPCs was comparable to that of controls, and FA-HAPCs were not apoptotic. This, according to the researchers, suggests a defect in FA-HAPCs’ ability to differentiate into hematopoietic and endothelial cells.

Further study of FA-HAPCs revealed significant downregulation of transcription factors that are critical for hematopoietic differentiation. This suggests the FA pathway might be involved in maintaining the transcriptional network critical for determining the differentiation propensity of HAPCs, the researchers said.

They also identified 227 genes that were significantly upregulated and 396 genes that were significantly downregulated in FA-HAPCs. The downregulated genes included those associated with mesodermal differentiation, vascular formation, and hematopoiesis.

“These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs,” Dr Saito said.

“Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.”

Dr Saito and colleagues described this research in STEM CELLS Translational Medicine.

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

Papers at a news stand

Media coverage of translational stem cell research might generate unrealistic expectations, according to a pair of researchers.

The team analyzed reports on stem cell research published in major daily newspapers in Canada, the US, and the UK between 2010 and 2013.

They found that most reports were highly optimistic about the future of stem cell therapies and indicated that therapies would be available for clinical use within 5 to 10 years or sooner.

The researchers said that, as spokespeople, scientists need to be mindful of harnessing public expectations.

“As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press,“ said Kalina Kamenova, PhD, of the University of Alberta in Edmonton, Canada.

Dr Kamenova conducted this research with Timothy Caulfield, also of the University of Alberta, and the pair disclosed their results in Science Translational Medicine.

The researchers examined 307 news reports covering translational research on stem cells, including human embryonic stem cells (21.5%), induced pluripotent stem cells (12.1%), cord blood stem cells (2.9%), other tissue-specific stem cells such as bone marrow or mesenchymal stem cells (23.8%), multiple types of stem cells (18.9%), and stem cells of an unspecified type (20.8%).

The team assessed perspectives on the future of stem cell therapies and found that 57.7% of news reports were optimistic, 10.4% were pessimistic, and 31.9% were neutral.

In addition, 69% of all news stories citing timelines predicted that stem cell therapies would be available within 5 to 10 years or sooner.

“The approval process for new treatments is long and complicated, and only a few of all drugs that enter preclinical testing are approved for human clinical trials,” Dr Kamenova pointed out. “It takes, on average, 12 years to get a new drug from the lab to the market and [an] additional 11 to 14 years of post-market surveillance.”

“Our findings showed that many scientists have often provided, either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies,” Caulfield added.

“[M]edia hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies. Care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner.”

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

SNOWMASS, COLO. – New-onset brain lesions arising after transcatheter aortic valve replacement are the largely unacknowledged elephant in the room with regard to the boomingly popular procedure.

Multiple studies utilizing diffusion-weighted MRI have shown roughly a 70% incidence of new brain lesions following transcatheter aortic valve replacement (TAVR). And studies employing full neurocognitive test batteries have consistently shown a relationship between small brain infarcts much like these, cognitive decline, and dementia, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

“This is an incredibly alarming piece of information. People should be aware of this. There is interest in doing TAVR in younger and younger patients. But there is indeed an issue with unintended consequences. If we take younger and less and less symptomatic patients, their chance of dementia in 20 years is probably going to be increased. We’re going to have to follow these patients for a long period of time to look at that specific endpoint,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn.

Speaking of unintended consequences, there is also the issue of TAVR-related stroke. Among the more than 27,000 patient records submitted to the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry through December 2014, the periprocedural stroke rate was 2.4%. One-year outcomes included 26.2% mortality and a 3.6% stroke rate.

Given that two-thirds of TAVR cases submitted to the TVT registry in 2014 involved patients age 80 or older, with New York Heart Association class III/IV symptoms present in 82%, and 50% of patients rated as being at extreme risk with a predicted 1-year mortality of 50% without intervention, a 3.6% stroke rate can be considered tolerable. But not so in the sort of younger asymptomatic patients with significant aortic stenosis increasingly under discussion as potential candidates for the procedure.

“Stroke rates are the real deal in patients undergoing TAVR. Maybe you’re going to take an asymptomatic person and give them a stroke rather than wait or give a surgical valve replacement,” the cardiologist said.

He predicted that within 10 years, the use of cerebral protection devices will be considered mandatory, not just during TAVR, but during percutaneous coronary intervention, CABG surgery, and probably during atrial fibrillation ablation as well. All of these procedures have been linked to new-onset brain lesions on diffusion-weighted MRI.

Promising new neuroprotection devices include Keystone Heart’s TriGuard, a filter-deflector that covers all three cerebral arteries, has no impact on cerebral blood flow, doesn’t require an additional access site, is supported by excellent safety data, and is approved in Europe but investigational in the United States, Dr. Holmes observed. Efficacy data are coming soon, when the results of the DETECT III (A Prospective Randomized Evaluation of The TriGuard HDH Embolic Deflection Device During Transcatheter Aortic Valve Replacement) will be presented at the ACC scientific sessions on March 15. In that study, 70 patients underwent neurocognitive testing before and 30 days after their TAVR procedure.

“We’re going to be using something – a filter or filter-deflector – in every single patient to prevent the abnormal brain hits that are seen with all of these procedures. The need for brain protection is not going away,” he forecast.

Dr. Holmes, who played a pivotal role in creating the TVT registry during his term as ACC president, pointed out an intriguing registry finding: Through 2014, only 36% of the procedures have been done percutaneously.

“When you go to meetings everybody says, ‘We do them all percutaneously with a dual Perclose.’ But when you look at the data, out of those 27,000 patients only about one-third were done percutaneously. Is that going to be different in the future? Probably. But it’s important to remember that we’re still not doing all that many percutaneous procedures,” the cardiologist said.

He reported serving as a consultant to Boston Scientific.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – An algorithm might predict whether patients with severe traumatic brain injury are recovering well or need interventions to preempt evolving intracranial hypertension.

“Valid predictive algorithms have the potential to revolutionize the care of patients with traumatic brain injury [TBI] and transform physiologic data from just a pure numeric value buried in a never-ending nursing flow sheet into a useful triage and decision-assist tool,” study author Dr. Brandon Bonds said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Patrice Wendling/Frontline Medical News

A minimum of 10 hours of continuous data on vital signs (intracranial pressure, heart rate, systolic blood pressure, shock index, and mean arterial pressure) were used to predict intracranial pressure (ICP) values for a retrospective cohort of 132 adults with severe TBI, 97% of which was the result of blunt trauma. Even relatively brief episodes of elevated ICP have been shown to be associated with poor outcomes in TBI patients, while marked elevation of ICP may lead to herniation and death, said Dr. Bonds of the R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore.

At the trauma center, vital signs are automatically collected every 6 seconds, 24 hours a day, on all TBI patients. This granularity of data was used to map patterns in the patients’ physiology. The approach used a nearest neighbor regression (NNR) method: A model was constructed that predicts future numerical values for an individual based on comparisons to data from historical subjects.

The same mathematical principal is used by a variety of industries to predict likely responses. NetFlix, for example, uses a system similar to the NNR method to predict future television and movie picks based on prior selections, Dr. Bonds explained.

About 20 minutes of continuously collected, automated vital sign data were then used to test the algorithm on a per-patient basis. The algorithm was used to predict future ICP values at 5 minutes to 2 hours from that time. The predictions are made on a rolling basis, with patient data updates every 5 minutes.

The NNR model was good at predicting actual ICP at 5 minutes, with a bias of 0.02 (± 2 standard deviations of 4 mm Hg). As expected, agreement was somewhat lessened at 2 hours (± 2 standard deviations of 10 mm Hg), “but this may still represent a clinically significant value,” Dr. Bonds said.

The next step is a prospective study of the algorithm’s utility.

Dr. Bonds said that NNR research really isn’t all that alien to medicine. Think about the experienced emergency physician who can look out into the wait room and “tell the nurse to bring back [a certain patient] because he didn’t look good,” Dr. Bonds said. Such a physician uses “the minimum amount of data he has and compares that patient to the historic data set of the thousands of patients that he’s seen previously to identify a patient that’s not going to do well. What we’re trying to do with this model is take this subjective skill and turn it into an objective tool.”

In an interview, session comoderator Dr. David A. Hampton, M.Eng., of Oregon Health and Science University in Portland, commented that he could definitely see the NNR method eventually having utility in severe TBI.

Future work will need to address outliers in the data because the standard deviation of 4 mm Hg “is pretty big for ICP swings” and to determine whether multiple libraries of data will need to be created based upon the different types of patients who come in, he said.

The study was funded by the United States Air Force. Dr. Bonds and his coauthors reported no financial disclosures.

[email protected]

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Avène Hydrating Sunscreen Lotions

Pierre Fabre Dermo-Cosmétique USA introduces 5 Avène Hydrating Sunscreen Lotions with sun protection factor 50+. The Hydrating Sunscreen Lotion contains avobenzone, homosalate, octisalate, and octocrylene for broad-spectrum UVA and UVB protection on the face and body with a smooth finish. The Ultra-Light Hydrating Sunscreen Lotion is suitable for the face with a matte finish. The Ultra-Light Hydrating Sunscreen Lotion Spray is fast absorbing with a sheer finish for application on the body. The Mineral Hydrating Sunscreen Lotions are available in light and ultra-light formulations. They offer sheer, nonwhitening, broad-spectrum UVA and UVB protection with both titanium dioxide and zinc oxide. The light formulation is suitable for the face and body, and the ultra-light formulation is suitable for the face. All of the sunscreens are water resistant for 80 minutes of water activity and are formulated with vitamin E (tocopheryl acetate) to provide antioxidant protection and glycerin for long-lasting hydration. These sunscreens will be available mid-March 2015. For more information, visit www.aveneusa.com.

cosmelan

Mesoestetic introduces cosmelan for the correction of pigmentary imperfections on the skin. This topical treatment eliminates dark spots by affecting melanocytes, which inhibits melanin production in hyperpigmented areas. As a result, spots disappear or are noticeably lightened. Its formula has antioxidant properties to enhance the skin’s radiance and even out skin tone. The cosmelan pack includes an intense depigmenting mask (cosmelan 1) and an oil-removing solution for skin cleansing and exfoliation, both for use in the physician’s office. It also contains a depigmenting maintenance cream (cosmelan 2) and hydra-vital factor k moisturizing cream, both for at-home use. The treatment consists of 2 phases: 1 or 2 sessions at the physician’s office with cosmelan 1, followed by at-home treatment (cosmelan 2) for 6 to 9 months. cosmelan is suitable for all skin types. For more information, visit www.mesoestetic.com.

Cresemba

Astellas Pharma US, Inc, announces approval of the investigational once-daily intravenous and oral broad-spectrum Cresemba (isavuconazonium) by the Anti-infective Drugs Advisory Committee of the US Food and Drug Administration. Cresemba is indicated for the treatment of invasive aspergillosis and invasive mucormycosis, both life-threatening fungal infections that predominately occur in immunocompromised patients. The review of the New Drug Application is expected to be completed in March 2015. For more information, visit www.astellas.us.

Glytone Lipid Recovery Cream

Pierre Fabre Dermo-Cosmétique USA introduces an enhanced Glytone Lipid Recovery Cream for use on inflamed and dry skin following cosmetic procedures such as chemical peels, lasers, microdermabrasion, and fillers. It contains camelina oil to preserve lipid barrier function; retinyl palmitate to repair damaged skin tissue; sodium hyaluronate to help skin cell proliferation and tissue repair; and shea butter, glycerin, and squalane to hydrate and moisturize. This postprocedure cream is now lighter in texture, allowing for faster absorption. Glytone Lipid Recovery Cream is physician dispensed. For more information, visit www.glytone-usa.com.

Opdivo

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Opdivo (nivolumab) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It works by inhibiting the PD-1 (programmed death receptor-1) protein on cells, which blocks the body’s immune system from attacking melanoma tumors. The indication represents accelerated approval based on tumor response rate and durability of response. For more information, visit www.opdivo.com.

Pazeo

Alcon, a Novartis company, receives US Food and Drug Administration approval of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7% for daily ocular itch relief associated with allergic conjunctivitis. It is administered one drop in each affected eye once daily and was approved with efficacy data at 24 hours following a dose. Pazeo is anticipated to be available by prescription in the United States in March 2015. For more information, visit www.myalcon.com/products/pharmaceutical/pazeo.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Blood for transfusion

Photo courtesy of UAB Hospital

Results of a large, randomized trial suggest a liberal transfusion strategy may benefit patients undergoing cardiac surgery.

Patients who received blood transfusions when their hemoglobin (Hb) levels were below 9 g/dL fared better than patients who only received transfusions once their Hb levels were below 7.5 g/dL.

The “low” Hb group had a slightly higher incidence of serious complications and a significantly higher rate of 90-day mortality than the “high” Hb group.

However, the researchers noted that the latter finding, while important, is difficult to interpret because the trial was not primarily designed to compare the difference in the number of deaths.

“Although only a hypothesis, the suggestion that it might be better rather than worse to transfuse patients who are only mildly anemic goes against the evidence about when to transfuse in non-cardiac surgery settings,” said Barnaby Reeves, DPhil, of the University of Bristol in the UK.

“Transfusing more rather than fewer patients would create a challenge for hospitals. With an aging population and possibly an increase in heart disease, obesity, and diabetes, it can only become more difficult in the future to maintain the national blood supply in the UK and in other developed countries around the world. Our findings emphasize the importance of interventions to reduce blood loss in the first place.”

Dr Reeves and his colleagues reported their findings in NEJM.

The team conducted their randomized, controlled trial to determine whether transfusing cardiac surgery patients at a lower Hb level would be safer or more cost-effective, as has been shown in other patient groups.

Individuals older than 16 who were undergoing non-emergency cardiac surgery were recruited to the trial at 17 UK hospitals. Patients with an Hb level of less than 9 g/dL after their operations were randomized to have a transfusion either when they became substantially anemic—with an Hb level of less than 7.5 g/dL—or right away, when they were mildly anemic—with an Hb level of less than 9 g/dL.

To compare the two transfusion strategies, the researchers assessed the incidence of serious infection, ischemic event, heart attack, infarction of the gut, and acute kidney injury in the first 3 months after the operation.

The team analyzed data for 2003 patients. Nearly all of the patients in the high Hb group received a transfusion (92.2%), compared to just over half of patients in the low Hb group (53.4%).

Slightly more patients in the low Hb group than the high Hb group had one or more of the aforementioned serious complications—35.1% and 33%, respectively (P=0.30). And significantly more patients had died at 90 days in the low Hb group than the high group—4.2% and 2.6%, respectively (P=0.045).

The researchers found no significant differences between the high and low Hb groups with respect to other information measured to assess recovery, but some of the other findings in the trial showed a trend in the same direction.

In addition, healthcare costs up to 3 months after surgery were similar in the high and low Hb groups.

“Even though the high group were given more blood, it was interesting that this did not lead to them costing more once the costs of treating complications were added to the analysis,” said Sarah Wordsworth, PhD, of the University of Oxford in the UK.

Based on the overall pattern of findings, the researchers proposed that a high or liberal transfusion threshold may be better after cardiac surgery. This challenges most prevailing guidelines and current health policy.

“Existing national and international transfusion guidelines recommend that blood transfusions only be given to patients who develop very low hemoglobin concentrations,” said Gavin Murphy, FRCS, of the University of Leicester in the UK.

“We have shown that this strategy may increase the number of deaths in cardiac surgery. This was the largest randomized trial ever conducted in the UK in a surgical or cardiac surgery population. It was the largest trial ever conducted that has considered indications for transfusion in cardiac surgery, and recruited over twice the number of patients recruited in all the previous trials put together. It . . .  recruited patients from the majority of [National Health Service] cardiac surgery centers in the UK and therefore reflects current UK practice and is relevant to UK patients.”

Blood for transfusion

Photo courtesy of UAB Hospital

Results of a large, randomized trial suggest a liberal transfusion strategy may benefit patients undergoing cardiac surgery.

Patients who received blood transfusions when their hemoglobin (Hb) levels were below 9 g/dL fared better than patients who only received transfusions once their Hb levels were below 7.5 g/dL.

The “low” Hb group had a slightly higher incidence of serious complications and a significantly higher rate of 90-day mortality than the “high” Hb group.

However, the researchers noted that the latter finding, while important, is difficult to interpret because the trial was not primarily designed to compare the difference in the number of deaths.

“Although only a hypothesis, the suggestion that it might be better rather than worse to transfuse patients who are only mildly anemic goes against the evidence about when to transfuse in non-cardiac surgery settings,” said Barnaby Reeves, DPhil, of the University of Bristol in the UK.

“Transfusing more rather than fewer patients would create a challenge for hospitals. With an aging population and possibly an increase in heart disease, obesity, and diabetes, it can only become more difficult in the future to maintain the national blood supply in the UK and in other developed countries around the world. Our findings emphasize the importance of interventions to reduce blood loss in the first place.”

Dr Reeves and his colleagues reported their findings in NEJM.

The team conducted their randomized, controlled trial to determine whether transfusing cardiac surgery patients at a lower Hb level would be safer or more cost-effective, as has been shown in other patient groups.

Individuals older than 16 who were undergoing non-emergency cardiac surgery were recruited to the trial at 17 UK hospitals. Patients with an Hb level of less than 9 g/dL after their operations were randomized to have a transfusion either when they became substantially anemic—with an Hb level of less than 7.5 g/dL—or right away, when they were mildly anemic—with an Hb level of less than 9 g/dL.

To compare the two transfusion strategies, the researchers assessed the incidence of serious infection, ischemic event, heart attack, infarction of the gut, and acute kidney injury in the first 3 months after the operation.

The team analyzed data for 2003 patients. Nearly all of the patients in the high Hb group received a transfusion (92.2%), compared to just over half of patients in the low Hb group (53.4%).

Slightly more patients in the low Hb group than the high Hb group had one or more of the aforementioned serious complications—35.1% and 33%, respectively (P=0.30). And significantly more patients had died at 90 days in the low Hb group than the high group—4.2% and 2.6%, respectively (P=0.045).

The researchers found no significant differences between the high and low Hb groups with respect to other information measured to assess recovery, but some of the other findings in the trial showed a trend in the same direction.

In addition, healthcare costs up to 3 months after surgery were similar in the high and low Hb groups.

“Even though the high group were given more blood, it was interesting that this did not lead to them costing more once the costs of treating complications were added to the analysis,” said Sarah Wordsworth, PhD, of the University of Oxford in the UK.

Based on the overall pattern of findings, the researchers proposed that a high or liberal transfusion threshold may be better after cardiac surgery. This challenges most prevailing guidelines and current health policy.

“Existing national and international transfusion guidelines recommend that blood transfusions only be given to patients who develop very low hemoglobin concentrations,” said Gavin Murphy, FRCS, of the University of Leicester in the UK.

“We have shown that this strategy may increase the number of deaths in cardiac surgery. This was the largest randomized trial ever conducted in the UK in a surgical or cardiac surgery population. It was the largest trial ever conducted that has considered indications for transfusion in cardiac surgery, and recruited over twice the number of patients recruited in all the previous trials put together. It . . .  recruited patients from the majority of [National Health Service] cardiac surgery centers in the UK and therefore reflects current UK practice and is relevant to UK patients.”

Blood for transfusion

Photo courtesy of UAB Hospital

Results of a large, randomized trial suggest a liberal transfusion strategy may benefit patients undergoing cardiac surgery.

Patients who received blood transfusions when their hemoglobin (Hb) levels were below 9 g/dL fared better than patients who only received transfusions once their Hb levels were below 7.5 g/dL.

The “low” Hb group had a slightly higher incidence of serious complications and a significantly higher rate of 90-day mortality than the “high” Hb group.

However, the researchers noted that the latter finding, while important, is difficult to interpret because the trial was not primarily designed to compare the difference in the number of deaths.

“Although only a hypothesis, the suggestion that it might be better rather than worse to transfuse patients who are only mildly anemic goes against the evidence about when to transfuse in non-cardiac surgery settings,” said Barnaby Reeves, DPhil, of the University of Bristol in the UK.

“Transfusing more rather than fewer patients would create a challenge for hospitals. With an aging population and possibly an increase in heart disease, obesity, and diabetes, it can only become more difficult in the future to maintain the national blood supply in the UK and in other developed countries around the world. Our findings emphasize the importance of interventions to reduce blood loss in the first place.”

Dr Reeves and his colleagues reported their findings in NEJM.

The team conducted their randomized, controlled trial to determine whether transfusing cardiac surgery patients at a lower Hb level would be safer or more cost-effective, as has been shown in other patient groups.

Individuals older than 16 who were undergoing non-emergency cardiac surgery were recruited to the trial at 17 UK hospitals. Patients with an Hb level of less than 9 g/dL after their operations were randomized to have a transfusion either when they became substantially anemic—with an Hb level of less than 7.5 g/dL—or right away, when they were mildly anemic—with an Hb level of less than 9 g/dL.

To compare the two transfusion strategies, the researchers assessed the incidence of serious infection, ischemic event, heart attack, infarction of the gut, and acute kidney injury in the first 3 months after the operation.

The team analyzed data for 2003 patients. Nearly all of the patients in the high Hb group received a transfusion (92.2%), compared to just over half of patients in the low Hb group (53.4%).

Slightly more patients in the low Hb group than the high Hb group had one or more of the aforementioned serious complications—35.1% and 33%, respectively (P=0.30). And significantly more patients had died at 90 days in the low Hb group than the high group—4.2% and 2.6%, respectively (P=0.045).

The researchers found no significant differences between the high and low Hb groups with respect to other information measured to assess recovery, but some of the other findings in the trial showed a trend in the same direction.

In addition, healthcare costs up to 3 months after surgery were similar in the high and low Hb groups.

“Even though the high group were given more blood, it was interesting that this did not lead to them costing more once the costs of treating complications were added to the analysis,” said Sarah Wordsworth, PhD, of the University of Oxford in the UK.

Based on the overall pattern of findings, the researchers proposed that a high or liberal transfusion threshold may be better after cardiac surgery. This challenges most prevailing guidelines and current health policy.

“Existing national and international transfusion guidelines recommend that blood transfusions only be given to patients who develop very low hemoglobin concentrations,” said Gavin Murphy, FRCS, of the University of Leicester in the UK.

“We have shown that this strategy may increase the number of deaths in cardiac surgery. This was the largest randomized trial ever conducted in the UK in a surgical or cardiac surgery population. It was the largest trial ever conducted that has considered indications for transfusion in cardiac surgery, and recruited over twice the number of patients recruited in all the previous trials put together. It . . .  recruited patients from the majority of [National Health Service] cardiac surgery centers in the UK and therefore reflects current UK practice and is relevant to UK patients.”

A sickled red blood cell

and a normal one

Image by Betty Pace

Gene editing via zinc-finger nucleases (ZFNs) shows early promise for treating sickle cell disease (SCD), according to preclinical research published in Blood.

Investigators used ZFNs to correct the SCD mutation in CD34⁺ hematopoietic stem and progenitor cells (HSPCs) derived from the bone marrow of SCD patients.

And these modified cells were able to produce normal red blood cells in vitro.

“This is a very exciting result,” said study author Donald Kohn, MD, of the University of California, Los Angeles.

“It suggests the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code.”

For this research, Dr Kohn and his colleagues took ZFNs designed to flank the SCD mutation and delivered them with a homologous donor template (either an integrase-defective lentiviral vector [IDLV] or a DNA oligonucleotide).

The investigators first tested this gene-editing system in CD34⁺ HSPCs derived from healthy donors and observed “high levels” of gene modification at the beta-globin locus. They also discovered off-target cleavage in the delta-globin gene but noted that this gene is “functionally dispensable.”

Additional experiments revealed that the modified CD34⁺ HSPCs could differentiate into erythroid, myeloid, and lymphoid cell types in vitro and in NSG mice.

So the investigators tested ZFN messenger RNA and the IDLV donor in CD34⁺ cells derived from the bone marrow of SCD patients. The team cultured cells in erythroid expansion medium and, after expansion but before enucleation, harvested the cells.

Genomic analysis revealed correction of the SCD mutation in 18.4±6.7% of the reads, and with that came the production of wild-type hemoglobin.

The investigators said these results show that ZFNs can provide site-specific gene correction and lay the groundwork for a potential therapy to treat SCD. The next steps will be to make the gene correction process more efficient and conduct additional research to determine if the method is effective and safe enough to move to clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said Megan Hoban, a graduate student at UCLA. “The study data provide the foundational evidence that the method is viable.”

Another research group has reported similarly promising early results using induced pluripotent stem cells and CRISPR/Cas9 to correct the SCD mutation.

A sickled red blood cell

and a normal one

Image by Betty Pace

Gene editing via zinc-finger nucleases (ZFNs) shows early promise for treating sickle cell disease (SCD), according to preclinical research published in Blood.

Investigators used ZFNs to correct the SCD mutation in CD34⁺ hematopoietic stem and progenitor cells (HSPCs) derived from the bone marrow of SCD patients.

And these modified cells were able to produce normal red blood cells in vitro.

“This is a very exciting result,” said study author Donald Kohn, MD, of the University of California, Los Angeles.

“It suggests the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code.”

For this research, Dr Kohn and his colleagues took ZFNs designed to flank the SCD mutation and delivered them with a homologous donor template (either an integrase-defective lentiviral vector [IDLV] or a DNA oligonucleotide).

The investigators first tested this gene-editing system in CD34⁺ HSPCs derived from healthy donors and observed “high levels” of gene modification at the beta-globin locus. They also discovered off-target cleavage in the delta-globin gene but noted that this gene is “functionally dispensable.”

Additional experiments revealed that the modified CD34⁺ HSPCs could differentiate into erythroid, myeloid, and lymphoid cell types in vitro and in NSG mice.

So the investigators tested ZFN messenger RNA and the IDLV donor in CD34⁺ cells derived from the bone marrow of SCD patients. The team cultured cells in erythroid expansion medium and, after expansion but before enucleation, harvested the cells.

Genomic analysis revealed correction of the SCD mutation in 18.4±6.7% of the reads, and with that came the production of wild-type hemoglobin.

The investigators said these results show that ZFNs can provide site-specific gene correction and lay the groundwork for a potential therapy to treat SCD. The next steps will be to make the gene correction process more efficient and conduct additional research to determine if the method is effective and safe enough to move to clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said Megan Hoban, a graduate student at UCLA. “The study data provide the foundational evidence that the method is viable.”

Another research group has reported similarly promising early results using induced pluripotent stem cells and CRISPR/Cas9 to correct the SCD mutation.

A sickled red blood cell

and a normal one

Image by Betty Pace

Gene editing via zinc-finger nucleases (ZFNs) shows early promise for treating sickle cell disease (SCD), according to preclinical research published in Blood.

Investigators used ZFNs to correct the SCD mutation in CD34⁺ hematopoietic stem and progenitor cells (HSPCs) derived from the bone marrow of SCD patients.

And these modified cells were able to produce normal red blood cells in vitro.

“This is a very exciting result,” said study author Donald Kohn, MD, of the University of California, Los Angeles.

“It suggests the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code.”

For this research, Dr Kohn and his colleagues took ZFNs designed to flank the SCD mutation and delivered them with a homologous donor template (either an integrase-defective lentiviral vector [IDLV] or a DNA oligonucleotide).

The investigators first tested this gene-editing system in CD34⁺ HSPCs derived from healthy donors and observed “high levels” of gene modification at the beta-globin locus. They also discovered off-target cleavage in the delta-globin gene but noted that this gene is “functionally dispensable.”

Additional experiments revealed that the modified CD34⁺ HSPCs could differentiate into erythroid, myeloid, and lymphoid cell types in vitro and in NSG mice.

So the investigators tested ZFN messenger RNA and the IDLV donor in CD34⁺ cells derived from the bone marrow of SCD patients. The team cultured cells in erythroid expansion medium and, after expansion but before enucleation, harvested the cells.

Genomic analysis revealed correction of the SCD mutation in 18.4±6.7% of the reads, and with that came the production of wild-type hemoglobin.

The investigators said these results show that ZFNs can provide site-specific gene correction and lay the groundwork for a potential therapy to treat SCD. The next steps will be to make the gene correction process more efficient and conduct additional research to determine if the method is effective and safe enough to move to clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said Megan Hoban, a graduate student at UCLA. “The study data provide the foundational evidence that the method is viable.”

Another research group has reported similarly promising early results using induced pluripotent stem cells and CRISPR/Cas9 to correct the SCD mutation.

Syringe

The US Food and Drug Administration (FDA) is warning healthcare professionals not to use Treanda (bendamustine hydrochloride) solution with closed-system transfer devices (CSTD), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).

Most marketed CSTDs contain either polycarbonate or ABS. And these materials dissolve when they come into contact with N, N-dimethylacetamide (DMA), an ingredient in Treanda solution.

This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in healthcare professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

Discovering the incompatibility

Treanda, which is manufactured by Teva, is used to treat patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

Treanda is available as a solution—Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution)—and a lyophilized powder—Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder).

The incompatibility of DMA with polycarbonate and ABS is only an issue with Treanda solution—not the lyophilized powder.

Since December 2014, Teva has received 40 complaints of the incompatibility issue, which was recently brought to the FDA’s attention. The agency also received a notification of device incompatibility with Treanda solution from a pharmacist.

These incompatibility issues included leaking of the CSTD, breaking or operational failure of the CSTD components, and a cloudy appearance or presence of particulate matter in the intravenous bag after dilution. To date, no adverse events have been reported related to the incompatibility.

FDA recommendations

The FDA has required label changes for both the solution and the powder formulations of Treanda to reflect the following safe preparation information.

The agency is recommending that healthcare professionals use Treanda solution only with polypropylene syringes containing a metal needle and a polypropylene hub. Polypropylene syringes are translucent in appearance.

Treanda solution should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The solution must be withdrawn and transferred for dilution in a biosafety cabinet or containment isolator.

If they aim to use a CSTD with Treanda solution, healthcare professionals should verify with the CSTD manufacturer or Teva US Medical Information (1-800-896-5855) that the CSTD is compatible with Treanda solution before preparing the drug.

Alternatively, healthcare professionals can use Treanda lyophilized powder with a CSTD. The solution and lyophilized powder formulations of Treanda should not be mixed.

For additional details on safe preparation of Treanda solution and lyophilized powder, see Teva’s Dear Health Care Provider letter.

Adverse events or quality problems associated with the use of Treanda products can be reported to the FDA’s MedWatch Adverse Event Reporting Program.

Syringe

The US Food and Drug Administration (FDA) is warning healthcare professionals not to use Treanda (bendamustine hydrochloride) solution with closed-system transfer devices (CSTD), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).

Most marketed CSTDs contain either polycarbonate or ABS. And these materials dissolve when they come into contact with N, N-dimethylacetamide (DMA), an ingredient in Treanda solution.

This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in healthcare professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

Discovering the incompatibility

Treanda, which is manufactured by Teva, is used to treat patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

Treanda is available as a solution—Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution)—and a lyophilized powder—Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder).

The incompatibility of DMA with polycarbonate and ABS is only an issue with Treanda solution—not the lyophilized powder.

Since December 2014, Teva has received 40 complaints of the incompatibility issue, which was recently brought to the FDA’s attention. The agency also received a notification of device incompatibility with Treanda solution from a pharmacist.

These incompatibility issues included leaking of the CSTD, breaking or operational failure of the CSTD components, and a cloudy appearance or presence of particulate matter in the intravenous bag after dilution. To date, no adverse events have been reported related to the incompatibility.

FDA recommendations

The FDA has required label changes for both the solution and the powder formulations of Treanda to reflect the following safe preparation information.

The agency is recommending that healthcare professionals use Treanda solution only with polypropylene syringes containing a metal needle and a polypropylene hub. Polypropylene syringes are translucent in appearance.

Treanda solution should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The solution must be withdrawn and transferred for dilution in a biosafety cabinet or containment isolator.

If they aim to use a CSTD with Treanda solution, healthcare professionals should verify with the CSTD manufacturer or Teva US Medical Information (1-800-896-5855) that the CSTD is compatible with Treanda solution before preparing the drug.

Alternatively, healthcare professionals can use Treanda lyophilized powder with a CSTD. The solution and lyophilized powder formulations of Treanda should not be mixed.

For additional details on safe preparation of Treanda solution and lyophilized powder, see Teva’s Dear Health Care Provider letter.

Adverse events or quality problems associated with the use of Treanda products can be reported to the FDA’s MedWatch Adverse Event Reporting Program.

Syringe

The US Food and Drug Administration (FDA) is warning healthcare professionals not to use Treanda (bendamustine hydrochloride) solution with closed-system transfer devices (CSTD), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).

Most marketed CSTDs contain either polycarbonate or ABS. And these materials dissolve when they come into contact with N, N-dimethylacetamide (DMA), an ingredient in Treanda solution.

This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in healthcare professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

Discovering the incompatibility

Treanda, which is manufactured by Teva, is used to treat patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

Treanda is available as a solution—Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution)—and a lyophilized powder—Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder).

The incompatibility of DMA with polycarbonate and ABS is only an issue with Treanda solution—not the lyophilized powder.

Since December 2014, Teva has received 40 complaints of the incompatibility issue, which was recently brought to the FDA’s attention. The agency also received a notification of device incompatibility with Treanda solution from a pharmacist.

These incompatibility issues included leaking of the CSTD, breaking or operational failure of the CSTD components, and a cloudy appearance or presence of particulate matter in the intravenous bag after dilution. To date, no adverse events have been reported related to the incompatibility.

FDA recommendations

The FDA has required label changes for both the solution and the powder formulations of Treanda to reflect the following safe preparation information.

The agency is recommending that healthcare professionals use Treanda solution only with polypropylene syringes containing a metal needle and a polypropylene hub. Polypropylene syringes are translucent in appearance.

Treanda solution should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The solution must be withdrawn and transferred for dilution in a biosafety cabinet or containment isolator.

If they aim to use a CSTD with Treanda solution, healthcare professionals should verify with the CSTD manufacturer or Teva US Medical Information (1-800-896-5855) that the CSTD is compatible with Treanda solution before preparing the drug.

Alternatively, healthcare professionals can use Treanda lyophilized powder with a CSTD. The solution and lyophilized powder formulations of Treanda should not be mixed.

For additional details on safe preparation of Treanda solution and lyophilized powder, see Teva’s Dear Health Care Provider letter.

Adverse events or quality problems associated with the use of Treanda products can be reported to the FDA’s MedWatch Adverse Event Reporting Program.