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Group creates model of arterial thrombus formation
Image by Andre E.X. Brown
A group of biophysicists have developed a mathematical model of arterial thrombus formation.
The team described the process of platelet aggregation as being similar to the video game Tetris and derived equations that allowed them to reproduce the wave process of platelet aggregate formation in a blood vessel.
Mikhail Panteleev, PhD, of Moscow State University in Russia, and his colleagues described this work in PLOS ONE.
Looking at thrombus formation in the same way as the tiles stack up in Tetris is a key aspect of the team’s model. In the game, the tiles either drop down onto a flat surface or become attached to parts sticking out from the rest of the block.
The researchers said there are only 2 differences between thrombus formation and the game.
Unlike in Tetris, when a layer of a thrombus is complete, it does not disappear. So, as time passes, a thrombus is capable of obstructing the space it is in.
And Tetris includes tiles of several different shapes. But, in a thrombus, the “falling tiles” are always the same—thrombocytes.
Having described the mathematical process of how vacant areas on the surface of a growing thrombus are filled, the researchers were able to build first a 1-dimensional model (as in Tetris) and then a 2-dimensional model (where thrombocytes are deposited in a dimensional plane).
At one point, the researchers began to consider certain thrombocytes as being dimensionless and the thrombus itself as being continuous. In other words, they went from a discrete model to a continuous model.
In a discrete model, the system under study consists of individual particles, and the behavior of each particle can be tracked individually. In a continuous model, the system under study consists of solid objects that can freely change their size or any other characteristic.
The sequential solution of the equations enabled the researchers to reproduce the dynamics of thrombus growth and study clot behavior under various conditions—in the case of damage to the vascular wall, for example.
Active media and autowaves
The researchers said the process of thrombus formation is like an autowave. And the blood, which carries platelets and proteins for coagulation, is an active medium.
The term “active medium” plays a key role in non-linear dynamics—the science of mathematical modeling of a range of systems, from mixtures of interacting chemicals and lasers to forest fires and even social networks.
One way to describe an active medium is to use the example of a forest fire. Every dry tree is not simply a passive object but a potential source of thermal energy. If there is a fire near a dry tree, it too will start to burn and provide more heat, which can then ignite other trees. The ability of elements in the system to release energy is a key feature of an active medium.
In active media, a local event (lightning striking a tree, for example) can initiate a transition process in a system from one state to another (in this case, a dry tree becomes a burning tree).
This process spreads like a wave in space, and the specific physical nature of the system is not so important. The same equation can be used to describe entirely different cases.
The term “autowave” means the wave propagation process is not passive, as in the case of seismic waves traveling from an earthquake’s epicenter, but active. At each point, the wave receives more energy.
In the case of thrombus formation, these terms apply to thrombocytes flowing in plasma. The thrombocytes can go from a free-flowing state to a deposited state.
Under normal circumstances, thrombocytes flow freely in the bloodstream, but if the vascular wall becomes damaged, they start to adhere to one another and to the vascular wall.
The blood also contains proteins required for thrombus formation. Even if there are no thrombocytes, reactions with these proteins are able to help form a clot to block a damaged vessel, and these reactions also occur in the form of autowaves.
Normally, thrombi prevent blood loss in the human body when a blood vessel has become damaged. Sometimes, however, thrombus formation occurs not as a result of an injury with damage to a blood vessel, but as a result of a reaction to a pathological process.
This type of thrombus formation can block a vessel completely and cut off the blood supply to tissues and organs. This, in turn, can lead to myocardial infarction, stroke, or gangrene of the extremities.
The researchers say their new model correctly describes arterial thrombus formation. These particular thrombi consist mainly of thrombocytes, and blood proteins play a relatively small role in the process.
“We have always had difficulty working with arterial blood clots in particular, in terms of developing and implementing computer models, because the subject involves a very difficult combination of mechanics (cell attachments), hydrodynamics with variable geometry, and biochemistry,” Dr Panteleev said.
“In our paper in PLOS ONE, we tried to use the most primitive description of a thrombus as a continuous medium, rather than discrete particles. This approximation is rough in many respects, and it limits the scope of the research, but it is able to give us some common patterns.”
“On the one hand, we plan to continue to apply it to specific tasks, as far as is possible, and on the other hand, we are developing more sophisticated and advanced models with 3-dimensional blood cells, the full mechanics of their interaction, and the proper biochemistry.” 
Image by Andre E.X. Brown
A group of biophysicists have developed a mathematical model of arterial thrombus formation.
The team described the process of platelet aggregation as being similar to the video game Tetris and derived equations that allowed them to reproduce the wave process of platelet aggregate formation in a blood vessel.
Mikhail Panteleev, PhD, of Moscow State University in Russia, and his colleagues described this work in PLOS ONE.
Looking at thrombus formation in the same way as the tiles stack up in Tetris is a key aspect of the team’s model. In the game, the tiles either drop down onto a flat surface or become attached to parts sticking out from the rest of the block.
The researchers said there are only 2 differences between thrombus formation and the game.
Unlike in Tetris, when a layer of a thrombus is complete, it does not disappear. So, as time passes, a thrombus is capable of obstructing the space it is in.
And Tetris includes tiles of several different shapes. But, in a thrombus, the “falling tiles” are always the same—thrombocytes.
Having described the mathematical process of how vacant areas on the surface of a growing thrombus are filled, the researchers were able to build first a 1-dimensional model (as in Tetris) and then a 2-dimensional model (where thrombocytes are deposited in a dimensional plane).
At one point, the researchers began to consider certain thrombocytes as being dimensionless and the thrombus itself as being continuous. In other words, they went from a discrete model to a continuous model.
In a discrete model, the system under study consists of individual particles, and the behavior of each particle can be tracked individually. In a continuous model, the system under study consists of solid objects that can freely change their size or any other characteristic.
The sequential solution of the equations enabled the researchers to reproduce the dynamics of thrombus growth and study clot behavior under various conditions—in the case of damage to the vascular wall, for example.
Active media and autowaves
The researchers said the process of thrombus formation is like an autowave. And the blood, which carries platelets and proteins for coagulation, is an active medium.
The term “active medium” plays a key role in non-linear dynamics—the science of mathematical modeling of a range of systems, from mixtures of interacting chemicals and lasers to forest fires and even social networks.
One way to describe an active medium is to use the example of a forest fire. Every dry tree is not simply a passive object but a potential source of thermal energy. If there is a fire near a dry tree, it too will start to burn and provide more heat, which can then ignite other trees. The ability of elements in the system to release energy is a key feature of an active medium.
In active media, a local event (lightning striking a tree, for example) can initiate a transition process in a system from one state to another (in this case, a dry tree becomes a burning tree).
This process spreads like a wave in space, and the specific physical nature of the system is not so important. The same equation can be used to describe entirely different cases.
The term “autowave” means the wave propagation process is not passive, as in the case of seismic waves traveling from an earthquake’s epicenter, but active. At each point, the wave receives more energy.
In the case of thrombus formation, these terms apply to thrombocytes flowing in plasma. The thrombocytes can go from a free-flowing state to a deposited state.
Under normal circumstances, thrombocytes flow freely in the bloodstream, but if the vascular wall becomes damaged, they start to adhere to one another and to the vascular wall.
The blood also contains proteins required for thrombus formation. Even if there are no thrombocytes, reactions with these proteins are able to help form a clot to block a damaged vessel, and these reactions also occur in the form of autowaves.
Normally, thrombi prevent blood loss in the human body when a blood vessel has become damaged. Sometimes, however, thrombus formation occurs not as a result of an injury with damage to a blood vessel, but as a result of a reaction to a pathological process.
This type of thrombus formation can block a vessel completely and cut off the blood supply to tissues and organs. This, in turn, can lead to myocardial infarction, stroke, or gangrene of the extremities.
The researchers say their new model correctly describes arterial thrombus formation. These particular thrombi consist mainly of thrombocytes, and blood proteins play a relatively small role in the process.
“We have always had difficulty working with arterial blood clots in particular, in terms of developing and implementing computer models, because the subject involves a very difficult combination of mechanics (cell attachments), hydrodynamics with variable geometry, and biochemistry,” Dr Panteleev said.
“In our paper in PLOS ONE, we tried to use the most primitive description of a thrombus as a continuous medium, rather than discrete particles. This approximation is rough in many respects, and it limits the scope of the research, but it is able to give us some common patterns.”
“On the one hand, we plan to continue to apply it to specific tasks, as far as is possible, and on the other hand, we are developing more sophisticated and advanced models with 3-dimensional blood cells, the full mechanics of their interaction, and the proper biochemistry.”
Image by Andre E.X. Brown
A group of biophysicists have developed a mathematical model of arterial thrombus formation.
The team described the process of platelet aggregation as being similar to the video game Tetris and derived equations that allowed them to reproduce the wave process of platelet aggregate formation in a blood vessel.
Mikhail Panteleev, PhD, of Moscow State University in Russia, and his colleagues described this work in PLOS ONE.
Looking at thrombus formation in the same way as the tiles stack up in Tetris is a key aspect of the team’s model. In the game, the tiles either drop down onto a flat surface or become attached to parts sticking out from the rest of the block.
The researchers said there are only 2 differences between thrombus formation and the game.
Unlike in Tetris, when a layer of a thrombus is complete, it does not disappear. So, as time passes, a thrombus is capable of obstructing the space it is in.
And Tetris includes tiles of several different shapes. But, in a thrombus, the “falling tiles” are always the same—thrombocytes.
Having described the mathematical process of how vacant areas on the surface of a growing thrombus are filled, the researchers were able to build first a 1-dimensional model (as in Tetris) and then a 2-dimensional model (where thrombocytes are deposited in a dimensional plane).
At one point, the researchers began to consider certain thrombocytes as being dimensionless and the thrombus itself as being continuous. In other words, they went from a discrete model to a continuous model.
In a discrete model, the system under study consists of individual particles, and the behavior of each particle can be tracked individually. In a continuous model, the system under study consists of solid objects that can freely change their size or any other characteristic.
The sequential solution of the equations enabled the researchers to reproduce the dynamics of thrombus growth and study clot behavior under various conditions—in the case of damage to the vascular wall, for example.
Active media and autowaves
The researchers said the process of thrombus formation is like an autowave. And the blood, which carries platelets and proteins for coagulation, is an active medium.
The term “active medium” plays a key role in non-linear dynamics—the science of mathematical modeling of a range of systems, from mixtures of interacting chemicals and lasers to forest fires and even social networks.
One way to describe an active medium is to use the example of a forest fire. Every dry tree is not simply a passive object but a potential source of thermal energy. If there is a fire near a dry tree, it too will start to burn and provide more heat, which can then ignite other trees. The ability of elements in the system to release energy is a key feature of an active medium.
In active media, a local event (lightning striking a tree, for example) can initiate a transition process in a system from one state to another (in this case, a dry tree becomes a burning tree).
This process spreads like a wave in space, and the specific physical nature of the system is not so important. The same equation can be used to describe entirely different cases.
The term “autowave” means the wave propagation process is not passive, as in the case of seismic waves traveling from an earthquake’s epicenter, but active. At each point, the wave receives more energy.
In the case of thrombus formation, these terms apply to thrombocytes flowing in plasma. The thrombocytes can go from a free-flowing state to a deposited state.
Under normal circumstances, thrombocytes flow freely in the bloodstream, but if the vascular wall becomes damaged, they start to adhere to one another and to the vascular wall.
The blood also contains proteins required for thrombus formation. Even if there are no thrombocytes, reactions with these proteins are able to help form a clot to block a damaged vessel, and these reactions also occur in the form of autowaves.
Normally, thrombi prevent blood loss in the human body when a blood vessel has become damaged. Sometimes, however, thrombus formation occurs not as a result of an injury with damage to a blood vessel, but as a result of a reaction to a pathological process.
This type of thrombus formation can block a vessel completely and cut off the blood supply to tissues and organs. This, in turn, can lead to myocardial infarction, stroke, or gangrene of the extremities.
The researchers say their new model correctly describes arterial thrombus formation. These particular thrombi consist mainly of thrombocytes, and blood proteins play a relatively small role in the process.
“We have always had difficulty working with arterial blood clots in particular, in terms of developing and implementing computer models, because the subject involves a very difficult combination of mechanics (cell attachments), hydrodynamics with variable geometry, and biochemistry,” Dr Panteleev said.
“In our paper in PLOS ONE, we tried to use the most primitive description of a thrombus as a continuous medium, rather than discrete particles. This approximation is rough in many respects, and it limits the scope of the research, but it is able to give us some common patterns.”
“On the one hand, we plan to continue to apply it to specific tasks, as far as is possible, and on the other hand, we are developing more sophisticated and advanced models with 3-dimensional blood cells, the full mechanics of their interaction, and the proper biochemistry.”
Tools may provide better genome analysis
Photo by Darren Baker
Scientists say they have developed 2 types of data analysis software that could help genomics researchers identify genetic drivers of disease with greater efficiency and accuracy.
Details on these tools were published in PLOS Computational Biology and Scientific Reports.
The first tool, MEGENA (for Multiscale Embedded Gene Co-expression Network Analysis), projects gene expression data onto a 3-dimensional sphere.
This allows scientists to study hierarchical organizational patterns in complex networks that are characteristic of diseases such as cancer, obesity, and Alzheimer’s disease.
When tested on data from The Cancer Genome Atlas (TCGA), MEGENA identified novel regulatory targets in breast and lung cancers, outperforming other co-expression analysis methods.
The second tool, SuperExactTest, establishes the first theoretical framework for assessing the statistical significance of multi-set intersections and enables users to compare large sets of data, such as gene sets produced from genome-wide association studies (GWAS) and differential expression analysis.
Scientists ran SuperExactTest on existing TCGA and GWAS data, identifying a core set of cancer genes and detecting related patterns among complex diseases.
Both tools come from the Multiscale Network Modeling Laboratory, led by Bin Zhang, PhD, an associate professor at Icahn School of Medicine at Mount Sinai in New York, New York.
“These tools fill important and unmet needs in genomics,” Dr Zhang said. “MEGENA will help scientists flesh out novel pathways and key targets in complex diseases, while SuperExactTest will provide a clearer understanding of the genome by comparing a large number of gene signatures.”
MEGENA and SuperExactTest are available as R packages on Dr Zhang’s website and CRAN (the Comprehensive R Archive Network), a repository of open-source software.
Photo by Darren Baker
Scientists say they have developed 2 types of data analysis software that could help genomics researchers identify genetic drivers of disease with greater efficiency and accuracy.
Details on these tools were published in PLOS Computational Biology and Scientific Reports.
The first tool, MEGENA (for Multiscale Embedded Gene Co-expression Network Analysis), projects gene expression data onto a 3-dimensional sphere.
This allows scientists to study hierarchical organizational patterns in complex networks that are characteristic of diseases such as cancer, obesity, and Alzheimer’s disease.
When tested on data from The Cancer Genome Atlas (TCGA), MEGENA identified novel regulatory targets in breast and lung cancers, outperforming other co-expression analysis methods.
The second tool, SuperExactTest, establishes the first theoretical framework for assessing the statistical significance of multi-set intersections and enables users to compare large sets of data, such as gene sets produced from genome-wide association studies (GWAS) and differential expression analysis.
Scientists ran SuperExactTest on existing TCGA and GWAS data, identifying a core set of cancer genes and detecting related patterns among complex diseases.
Both tools come from the Multiscale Network Modeling Laboratory, led by Bin Zhang, PhD, an associate professor at Icahn School of Medicine at Mount Sinai in New York, New York.
“These tools fill important and unmet needs in genomics,” Dr Zhang said. “MEGENA will help scientists flesh out novel pathways and key targets in complex diseases, while SuperExactTest will provide a clearer understanding of the genome by comparing a large number of gene signatures.”
MEGENA and SuperExactTest are available as R packages on Dr Zhang’s website and CRAN (the Comprehensive R Archive Network), a repository of open-source software.
Photo by Darren Baker
Scientists say they have developed 2 types of data analysis software that could help genomics researchers identify genetic drivers of disease with greater efficiency and accuracy.
Details on these tools were published in PLOS Computational Biology and Scientific Reports.
The first tool, MEGENA (for Multiscale Embedded Gene Co-expression Network Analysis), projects gene expression data onto a 3-dimensional sphere.
This allows scientists to study hierarchical organizational patterns in complex networks that are characteristic of diseases such as cancer, obesity, and Alzheimer’s disease.
When tested on data from The Cancer Genome Atlas (TCGA), MEGENA identified novel regulatory targets in breast and lung cancers, outperforming other co-expression analysis methods.
The second tool, SuperExactTest, establishes the first theoretical framework for assessing the statistical significance of multi-set intersections and enables users to compare large sets of data, such as gene sets produced from genome-wide association studies (GWAS) and differential expression analysis.
Scientists ran SuperExactTest on existing TCGA and GWAS data, identifying a core set of cancer genes and detecting related patterns among complex diseases.
Both tools come from the Multiscale Network Modeling Laboratory, led by Bin Zhang, PhD, an associate professor at Icahn School of Medicine at Mount Sinai in New York, New York.
“These tools fill important and unmet needs in genomics,” Dr Zhang said. “MEGENA will help scientists flesh out novel pathways and key targets in complex diseases, while SuperExactTest will provide a clearer understanding of the genome by comparing a large number of gene signatures.”
MEGENA and SuperExactTest are available as R packages on Dr Zhang’s website and CRAN (the Comprehensive R Archive Network), a repository of open-source software.
Climate change may alter malaria risk in Africa
Photo by James Gathany
A larger portion of Africa is at high risk for malaria transmission than previously predicted, according to a mapping study published in Vector-Borne and Zoonotic Diseases.
The research also suggests that, under future climate regimes, the area where the disease can be transmitted most easily will shrink, but the total
malaria transmission zone in Africa will expand and move into new territory.
Researchers estimate that, by 2080, the year-round, highest-risk transmission zone will move from coastal West Africa, east to the Albertine Rift, between the Democratic Republic of Congo and Uganda.
The area suitable for seasonal, lower-risk transmission will shift north into coastal sub-Saharan Africa.
In addition, some parts of Africa will become too hot for malaria.
The overall expansion of malaria-vulnerable areas will challenge management of the deadly disease, said study author Sadie Ryan, PhD, of the University of Florida in Gainesville.
She noted that malaria will arrive in new areas, posing a risk to new populations, and the shift of endemic and epidemic areas will require public health management changes.
“Mapping a mathematical predictive model of a climate-driven infectious disease like malaria allows us to develop tools to understand both spatial and seasonal dynamics, and to anticipate the future changes to those dynamics,” Dr Ryan said.
She and her colleagues used a model that takes into account how mosquitoes and the malaria parasite respond to temperature. This model shows an optimal transmission temperature for malaria that, at 25 degrees Celsius, is 6 degrees lower than previous predictive models.
Dr Ryan said this work will play an important role in helping public health officials and non-governmental organizations plan for the efficient deployment of resources and interventions to control future outbreaks of malaria and their associated societal costs.
This study expands upon the team’s prior work at the National Center for Ecological Analysis and Synthesis at the University of California, Santa Barbara.
Photo by James Gathany
A larger portion of Africa is at high risk for malaria transmission than previously predicted, according to a mapping study published in Vector-Borne and Zoonotic Diseases.
The research also suggests that, under future climate regimes, the area where the disease can be transmitted most easily will shrink, but the total
malaria transmission zone in Africa will expand and move into new territory.
Researchers estimate that, by 2080, the year-round, highest-risk transmission zone will move from coastal West Africa, east to the Albertine Rift, between the Democratic Republic of Congo and Uganda.
The area suitable for seasonal, lower-risk transmission will shift north into coastal sub-Saharan Africa.
In addition, some parts of Africa will become too hot for malaria.
The overall expansion of malaria-vulnerable areas will challenge management of the deadly disease, said study author Sadie Ryan, PhD, of the University of Florida in Gainesville.
She noted that malaria will arrive in new areas, posing a risk to new populations, and the shift of endemic and epidemic areas will require public health management changes.
“Mapping a mathematical predictive model of a climate-driven infectious disease like malaria allows us to develop tools to understand both spatial and seasonal dynamics, and to anticipate the future changes to those dynamics,” Dr Ryan said.
She and her colleagues used a model that takes into account how mosquitoes and the malaria parasite respond to temperature. This model shows an optimal transmission temperature for malaria that, at 25 degrees Celsius, is 6 degrees lower than previous predictive models.
Dr Ryan said this work will play an important role in helping public health officials and non-governmental organizations plan for the efficient deployment of resources and interventions to control future outbreaks of malaria and their associated societal costs.
This study expands upon the team’s prior work at the National Center for Ecological Analysis and Synthesis at the University of California, Santa Barbara.
Photo by James Gathany
A larger portion of Africa is at high risk for malaria transmission than previously predicted, according to a mapping study published in Vector-Borne and Zoonotic Diseases.
The research also suggests that, under future climate regimes, the area where the disease can be transmitted most easily will shrink, but the total
malaria transmission zone in Africa will expand and move into new territory.
Researchers estimate that, by 2080, the year-round, highest-risk transmission zone will move from coastal West Africa, east to the Albertine Rift, between the Democratic Republic of Congo and Uganda.
The area suitable for seasonal, lower-risk transmission will shift north into coastal sub-Saharan Africa.
In addition, some parts of Africa will become too hot for malaria.
The overall expansion of malaria-vulnerable areas will challenge management of the deadly disease, said study author Sadie Ryan, PhD, of the University of Florida in Gainesville.
She noted that malaria will arrive in new areas, posing a risk to new populations, and the shift of endemic and epidemic areas will require public health management changes.
“Mapping a mathematical predictive model of a climate-driven infectious disease like malaria allows us to develop tools to understand both spatial and seasonal dynamics, and to anticipate the future changes to those dynamics,” Dr Ryan said.
She and her colleagues used a model that takes into account how mosquitoes and the malaria parasite respond to temperature. This model shows an optimal transmission temperature for malaria that, at 25 degrees Celsius, is 6 degrees lower than previous predictive models.
Dr Ryan said this work will play an important role in helping public health officials and non-governmental organizations plan for the efficient deployment of resources and interventions to control future outbreaks of malaria and their associated societal costs.
This study expands upon the team’s prior work at the National Center for Ecological Analysis and Synthesis at the University of California, Santa Barbara.
Complete excision most effective for BI-ALCL
Photo courtesy of the FDA
The optimal treatment approach for most women with breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is complete surgical excision of the implant and surrounding capsule, a new study suggests.
The study, published in the Journal of Clinical Oncology, represents the most comprehensive study of BI-ALCL to date, including 87 patients and 30 investigators from 14 institutions across 5 continents.
BI-ALCL is a rare T-cell lymphoma that forms in the scar tissue or in the fluid surrounding a breast implant. The disease manifests as a large fluid collection around the implant over a year after implantation, usually taking an average of 8 years to develop.
An estimated 10 million women worldwide have breast implants, and the annual incidence of BI-ALCL is estimated to be 0.1 to 0.3 per 100,000 women with breast implants.
“Although this disease is rare, it appears to be amenable to treatment, and, in the vast majority of patients, the outcome is very good,” said Mark Clemens, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“The disease can be reliably diagnosed, and, when treated appropriately, it has a good prognosis.”
Still, the optimal management for BI-ALCL hasn’t been clear. So with this study, Dr Clemens and his colleagues sought to evaluate treatment efficacy on disease outcomes and determine the best treatment approach. The study expands on previous research published in the Journal of Clinical Oncology in 2014.
The researchers gathered detailed treatment and outcome information from a total of 87 BI-ALCL patients, including 37 whose information had not previously been published. A review of treatment approaches in relation to event-free survival and overall survival revealed that surgery was the optimal frontline therapy for BI-ALCL.
“We determined that complete surgical excision was essential for the management of this disease,” Dr Clemens said. “Patients did not do as well unless they were treated with full removal of the breast implant and complete excision of the capsule around the implant.”
Patients with complete surgical excision had a recurrence rate of 4% at 5 years, compared to 28% for patients who received radiation therapy and 32% for chemotherapy.
In addition, patients who underwent a complete surgical excision had better overall survival (P=0.022) and event-free survival (P=0.014) than patients who received a partial capsulectomy, systemic chemotherapy, or radiation.
“This lymphoma represents a different paradigm from systemic anaplastic large-cell lymphoma, in particular because of its strong association with breast implants,” said Roberto N. Miranda, MD, of The University of Texas MD Anderson Cancer Center.
“We have demonstrated that this is a predominantly localized disease where surgical excision has a primary role.”
The researchers emphasized that, despite the overall good prognosis, some rare cases of BI-ALCL exhibit more aggressive behavior with systemic dissemination. As a part of this study, the team is gathering tissue from these patients to assess underlying mechanisms for progression of disease.
Additional research is ongoing to optimize therapy for these cases through genetic profiling and defining the role of chemotherapy and radiation. The researchers are also studying animal models to further assess the role of breast implants in the pathogenesis of this lymphoma.
Photo courtesy of the FDA
The optimal treatment approach for most women with breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is complete surgical excision of the implant and surrounding capsule, a new study suggests.
The study, published in the Journal of Clinical Oncology, represents the most comprehensive study of BI-ALCL to date, including 87 patients and 30 investigators from 14 institutions across 5 continents.
BI-ALCL is a rare T-cell lymphoma that forms in the scar tissue or in the fluid surrounding a breast implant. The disease manifests as a large fluid collection around the implant over a year after implantation, usually taking an average of 8 years to develop.
An estimated 10 million women worldwide have breast implants, and the annual incidence of BI-ALCL is estimated to be 0.1 to 0.3 per 100,000 women with breast implants.
“Although this disease is rare, it appears to be amenable to treatment, and, in the vast majority of patients, the outcome is very good,” said Mark Clemens, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“The disease can be reliably diagnosed, and, when treated appropriately, it has a good prognosis.”
Still, the optimal management for BI-ALCL hasn’t been clear. So with this study, Dr Clemens and his colleagues sought to evaluate treatment efficacy on disease outcomes and determine the best treatment approach. The study expands on previous research published in the Journal of Clinical Oncology in 2014.
The researchers gathered detailed treatment and outcome information from a total of 87 BI-ALCL patients, including 37 whose information had not previously been published. A review of treatment approaches in relation to event-free survival and overall survival revealed that surgery was the optimal frontline therapy for BI-ALCL.
“We determined that complete surgical excision was essential for the management of this disease,” Dr Clemens said. “Patients did not do as well unless they were treated with full removal of the breast implant and complete excision of the capsule around the implant.”
Patients with complete surgical excision had a recurrence rate of 4% at 5 years, compared to 28% for patients who received radiation therapy and 32% for chemotherapy.
In addition, patients who underwent a complete surgical excision had better overall survival (P=0.022) and event-free survival (P=0.014) than patients who received a partial capsulectomy, systemic chemotherapy, or radiation.
“This lymphoma represents a different paradigm from systemic anaplastic large-cell lymphoma, in particular because of its strong association with breast implants,” said Roberto N. Miranda, MD, of The University of Texas MD Anderson Cancer Center.
“We have demonstrated that this is a predominantly localized disease where surgical excision has a primary role.”
The researchers emphasized that, despite the overall good prognosis, some rare cases of BI-ALCL exhibit more aggressive behavior with systemic dissemination. As a part of this study, the team is gathering tissue from these patients to assess underlying mechanisms for progression of disease.
Additional research is ongoing to optimize therapy for these cases through genetic profiling and defining the role of chemotherapy and radiation. The researchers are also studying animal models to further assess the role of breast implants in the pathogenesis of this lymphoma.
Photo courtesy of the FDA
The optimal treatment approach for most women with breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is complete surgical excision of the implant and surrounding capsule, a new study suggests.
The study, published in the Journal of Clinical Oncology, represents the most comprehensive study of BI-ALCL to date, including 87 patients and 30 investigators from 14 institutions across 5 continents.
BI-ALCL is a rare T-cell lymphoma that forms in the scar tissue or in the fluid surrounding a breast implant. The disease manifests as a large fluid collection around the implant over a year after implantation, usually taking an average of 8 years to develop.
An estimated 10 million women worldwide have breast implants, and the annual incidence of BI-ALCL is estimated to be 0.1 to 0.3 per 100,000 women with breast implants.
“Although this disease is rare, it appears to be amenable to treatment, and, in the vast majority of patients, the outcome is very good,” said Mark Clemens, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“The disease can be reliably diagnosed, and, when treated appropriately, it has a good prognosis.”
Still, the optimal management for BI-ALCL hasn’t been clear. So with this study, Dr Clemens and his colleagues sought to evaluate treatment efficacy on disease outcomes and determine the best treatment approach. The study expands on previous research published in the Journal of Clinical Oncology in 2014.
The researchers gathered detailed treatment and outcome information from a total of 87 BI-ALCL patients, including 37 whose information had not previously been published. A review of treatment approaches in relation to event-free survival and overall survival revealed that surgery was the optimal frontline therapy for BI-ALCL.
“We determined that complete surgical excision was essential for the management of this disease,” Dr Clemens said. “Patients did not do as well unless they were treated with full removal of the breast implant and complete excision of the capsule around the implant.”
Patients with complete surgical excision had a recurrence rate of 4% at 5 years, compared to 28% for patients who received radiation therapy and 32% for chemotherapy.
In addition, patients who underwent a complete surgical excision had better overall survival (P=0.022) and event-free survival (P=0.014) than patients who received a partial capsulectomy, systemic chemotherapy, or radiation.
“This lymphoma represents a different paradigm from systemic anaplastic large-cell lymphoma, in particular because of its strong association with breast implants,” said Roberto N. Miranda, MD, of The University of Texas MD Anderson Cancer Center.
“We have demonstrated that this is a predominantly localized disease where surgical excision has a primary role.”
The researchers emphasized that, despite the overall good prognosis, some rare cases of BI-ALCL exhibit more aggressive behavior with systemic dissemination. As a part of this study, the team is gathering tissue from these patients to assess underlying mechanisms for progression of disease.
Additional research is ongoing to optimize therapy for these cases through genetic profiling and defining the role of chemotherapy and radiation. The researchers are also studying animal models to further assess the role of breast implants in the pathogenesis of this lymphoma.
Team identifies potential biomarkers for AML therapy
Photo by Kristin Gladney
New research published in Cell Reports has revealed biomarkers that may help predict which acute myeloid leukemia (AML) patients will respond to treatment with PU-H71.
This drug targets a tumor-enriched form of the protein Hsp90 called teHSP90, which is critical to the growth of cancer cells.
However, previous preclinical experiments showed that PU-H71 only kills some AML cells.
“We observed that only a subset of leukemia patient samples were sensitive to the drug,” said study author Monica Guzman, PhD, of Weill Cornell Medical College in New York, New York.
“We wanted to be able to identify which patients with leukemia would respond to this drug.”
So Dr Guzman and her colleagues focused on groups of proteins that function within signaling networks in leukemia cells.
The researchers found that 2 of these networks, JAK-STAT and PI3K-AKT, were important for leukemia cells to function. These signaling pathways are critical for the survival of AML cells, and they, in turn, are dependent on teHsp90.
The team treated AML cells with PU-H71 and found that cells with greater JAK-STAT and PI3K-AKT activity were killed by the drug. Cells with less active signaling networks did not respond to PU-H71.
“Higher activation of these networks makes the leukemia cells more dependent on Hsp90,” Dr Guzman said. “Since PU-H71 targets teHsp90, leukemia samples with these features are good targets for treatment with the drug.”
The next step for Dr Guzman’s team is to test their findings in patients. Ideally, the JAK-STAT and PI3K-AKT signaling pathways will serve as biomarkers for identifying patients whose leukemias will be sensitive to PU-H71.
“We are working on a tool that will quickly and easily identify patients whose cancers will respond to PU-H71,” Dr Guzman said. “We are really looking forward to seeing this in leukemic patients and being able to offer them a new treatment.”
Photo by Kristin Gladney
New research published in Cell Reports has revealed biomarkers that may help predict which acute myeloid leukemia (AML) patients will respond to treatment with PU-H71.
This drug targets a tumor-enriched form of the protein Hsp90 called teHSP90, which is critical to the growth of cancer cells.
However, previous preclinical experiments showed that PU-H71 only kills some AML cells.
“We observed that only a subset of leukemia patient samples were sensitive to the drug,” said study author Monica Guzman, PhD, of Weill Cornell Medical College in New York, New York.
“We wanted to be able to identify which patients with leukemia would respond to this drug.”
So Dr Guzman and her colleagues focused on groups of proteins that function within signaling networks in leukemia cells.
The researchers found that 2 of these networks, JAK-STAT and PI3K-AKT, were important for leukemia cells to function. These signaling pathways are critical for the survival of AML cells, and they, in turn, are dependent on teHsp90.
The team treated AML cells with PU-H71 and found that cells with greater JAK-STAT and PI3K-AKT activity were killed by the drug. Cells with less active signaling networks did not respond to PU-H71.
“Higher activation of these networks makes the leukemia cells more dependent on Hsp90,” Dr Guzman said. “Since PU-H71 targets teHsp90, leukemia samples with these features are good targets for treatment with the drug.”
The next step for Dr Guzman’s team is to test their findings in patients. Ideally, the JAK-STAT and PI3K-AKT signaling pathways will serve as biomarkers for identifying patients whose leukemias will be sensitive to PU-H71.
“We are working on a tool that will quickly and easily identify patients whose cancers will respond to PU-H71,” Dr Guzman said. “We are really looking forward to seeing this in leukemic patients and being able to offer them a new treatment.”
Photo by Kristin Gladney
New research published in Cell Reports has revealed biomarkers that may help predict which acute myeloid leukemia (AML) patients will respond to treatment with PU-H71.
This drug targets a tumor-enriched form of the protein Hsp90 called teHSP90, which is critical to the growth of cancer cells.
However, previous preclinical experiments showed that PU-H71 only kills some AML cells.
“We observed that only a subset of leukemia patient samples were sensitive to the drug,” said study author Monica Guzman, PhD, of Weill Cornell Medical College in New York, New York.
“We wanted to be able to identify which patients with leukemia would respond to this drug.”
So Dr Guzman and her colleagues focused on groups of proteins that function within signaling networks in leukemia cells.
The researchers found that 2 of these networks, JAK-STAT and PI3K-AKT, were important for leukemia cells to function. These signaling pathways are critical for the survival of AML cells, and they, in turn, are dependent on teHsp90.
The team treated AML cells with PU-H71 and found that cells with greater JAK-STAT and PI3K-AKT activity were killed by the drug. Cells with less active signaling networks did not respond to PU-H71.
“Higher activation of these networks makes the leukemia cells more dependent on Hsp90,” Dr Guzman said. “Since PU-H71 targets teHsp90, leukemia samples with these features are good targets for treatment with the drug.”
The next step for Dr Guzman’s team is to test their findings in patients. Ideally, the JAK-STAT and PI3K-AKT signaling pathways will serve as biomarkers for identifying patients whose leukemias will be sensitive to PU-H71.
“We are working on a tool that will quickly and easily identify patients whose cancers will respond to PU-H71,” Dr Guzman said. “We are really looking forward to seeing this in leukemic patients and being able to offer them a new treatment.”
Catheter approved to treat DVT
thrombectomy catheter
Image courtesy of
Boston Scientific
The AngioJet ZelanteDVT thrombectomy catheter has been approved for commercialization in the US and Europe.
The device received the CE mark and approval from the US Food and Drug Administration to treat deep vein thrombosis (DVT) in large-diameter
upper and lower limb peripheral veins.
The ZelanteDVT catheter was designed to remove large venous clot burdens and facilitate rapid restoration of blood flow, potentially decreasing procedural time, relieving symptoms, and reducing late complications.
The ZelanteDVT Thrombectomy Set is intended for use with the AngioJet Ultra Console to break apart and remove thrombi, including DVT, from iliofemoral and lower extremity veins greater than or equal to 6.0 mm in diameter and upper extremity peripheral veins greater than or equal to 6.0 mm in diameter.
The set is also intended for use with the AngioJet Power Pulse technique for the controlled and selective infusion of physician-specified fluids, including thrombolytic agents, into the peripheral vascular system.
The ZelanteDVT catheter is a product of Boston Scientific. For more information on the device, visit the company’s website.
thrombectomy catheter
Image courtesy of
Boston Scientific
The AngioJet ZelanteDVT thrombectomy catheter has been approved for commercialization in the US and Europe.
The device received the CE mark and approval from the US Food and Drug Administration to treat deep vein thrombosis (DVT) in large-diameter
upper and lower limb peripheral veins.
The ZelanteDVT catheter was designed to remove large venous clot burdens and facilitate rapid restoration of blood flow, potentially decreasing procedural time, relieving symptoms, and reducing late complications.
The ZelanteDVT Thrombectomy Set is intended for use with the AngioJet Ultra Console to break apart and remove thrombi, including DVT, from iliofemoral and lower extremity veins greater than or equal to 6.0 mm in diameter and upper extremity peripheral veins greater than or equal to 6.0 mm in diameter.
The set is also intended for use with the AngioJet Power Pulse technique for the controlled and selective infusion of physician-specified fluids, including thrombolytic agents, into the peripheral vascular system.
The ZelanteDVT catheter is a product of Boston Scientific. For more information on the device, visit the company’s website.
thrombectomy catheter
Image courtesy of
Boston Scientific
The AngioJet ZelanteDVT thrombectomy catheter has been approved for commercialization in the US and Europe.
The device received the CE mark and approval from the US Food and Drug Administration to treat deep vein thrombosis (DVT) in large-diameter
upper and lower limb peripheral veins.
The ZelanteDVT catheter was designed to remove large venous clot burdens and facilitate rapid restoration of blood flow, potentially decreasing procedural time, relieving symptoms, and reducing late complications.
The ZelanteDVT Thrombectomy Set is intended for use with the AngioJet Ultra Console to break apart and remove thrombi, including DVT, from iliofemoral and lower extremity veins greater than or equal to 6.0 mm in diameter and upper extremity peripheral veins greater than or equal to 6.0 mm in diameter.
The set is also intended for use with the AngioJet Power Pulse technique for the controlled and selective infusion of physician-specified fluids, including thrombolytic agents, into the peripheral vascular system.
The ZelanteDVT catheter is a product of Boston Scientific. For more information on the device, visit the company’s website.
Pediatric cancer deaths on the decline in UK
Photo by Bill Branson
The rate of pediatric cancer deaths in the UK has dropped by 24% in the last decade, according to new figures published by Cancer Research UK.
The latest figures suggest the number of children age 14 and younger dying from cancer each year in the UK has dropped from around 330 in the early 2000s (2001-2003) to around 260 in more recent years (2011-2013).
But this still means that about 5 children die from cancer every week in the UK.
The data suggest that around 1500 children are diagnosed with cancer every year in the UK. This is the annual average number of new cases for all children’s cancers (ages 0-14), excluding non-melanoma skin cancer, in the UK from 2010 to 2012.
The figures also indicate that overall survival for children’s cancers has tripled since the 1960s, and three quarters of children with cancer are cured.
“Although we’re losing fewer young lives to cancer, a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
The data on mortality according to cancer type spans the period from 1996 to 2005 and includes children ages 0 to 14 living in Great Britain (not the whole UK).
These data indicate that the average number of annual deaths for pediatric leukemias was 59.7 for males and 45.6 for females during the period analyzed. These deaths made up 30.3% and 29.6%, respectively, of all childhood cancer deaths.
The average number of annual deaths for pediatric lymphomas was 12 for males and 5.5 for females. These deaths made up 6.1% and 3.6%, respectively, of all childhood cancer deaths.
Cancer Research UK compiles UK-wide incidence data produced by the regional cancer registries in England and the 3 national registries in Wales, Scotland, and Northern Ireland for the UK statistics.
The organization must wait until all of the data has been published by each country before publishing the figures on the Cancer Research UK website.
Photo by Bill Branson
The rate of pediatric cancer deaths in the UK has dropped by 24% in the last decade, according to new figures published by Cancer Research UK.
The latest figures suggest the number of children age 14 and younger dying from cancer each year in the UK has dropped from around 330 in the early 2000s (2001-2003) to around 260 in more recent years (2011-2013).
But this still means that about 5 children die from cancer every week in the UK.
The data suggest that around 1500 children are diagnosed with cancer every year in the UK. This is the annual average number of new cases for all children’s cancers (ages 0-14), excluding non-melanoma skin cancer, in the UK from 2010 to 2012.
The figures also indicate that overall survival for children’s cancers has tripled since the 1960s, and three quarters of children with cancer are cured.
“Although we’re losing fewer young lives to cancer, a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
The data on mortality according to cancer type spans the period from 1996 to 2005 and includes children ages 0 to 14 living in Great Britain (not the whole UK).
These data indicate that the average number of annual deaths for pediatric leukemias was 59.7 for males and 45.6 for females during the period analyzed. These deaths made up 30.3% and 29.6%, respectively, of all childhood cancer deaths.
The average number of annual deaths for pediatric lymphomas was 12 for males and 5.5 for females. These deaths made up 6.1% and 3.6%, respectively, of all childhood cancer deaths.
Cancer Research UK compiles UK-wide incidence data produced by the regional cancer registries in England and the 3 national registries in Wales, Scotland, and Northern Ireland for the UK statistics.
The organization must wait until all of the data has been published by each country before publishing the figures on the Cancer Research UK website.
Photo by Bill Branson
The rate of pediatric cancer deaths in the UK has dropped by 24% in the last decade, according to new figures published by Cancer Research UK.
The latest figures suggest the number of children age 14 and younger dying from cancer each year in the UK has dropped from around 330 in the early 2000s (2001-2003) to around 260 in more recent years (2011-2013).
But this still means that about 5 children die from cancer every week in the UK.
The data suggest that around 1500 children are diagnosed with cancer every year in the UK. This is the annual average number of new cases for all children’s cancers (ages 0-14), excluding non-melanoma skin cancer, in the UK from 2010 to 2012.
The figures also indicate that overall survival for children’s cancers has tripled since the 1960s, and three quarters of children with cancer are cured.
“Although we’re losing fewer young lives to cancer, a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
The data on mortality according to cancer type spans the period from 1996 to 2005 and includes children ages 0 to 14 living in Great Britain (not the whole UK).
These data indicate that the average number of annual deaths for pediatric leukemias was 59.7 for males and 45.6 for females during the period analyzed. These deaths made up 30.3% and 29.6%, respectively, of all childhood cancer deaths.
The average number of annual deaths for pediatric lymphomas was 12 for males and 5.5 for females. These deaths made up 6.1% and 3.6%, respectively, of all childhood cancer deaths.
Cancer Research UK compiles UK-wide incidence data produced by the regional cancer registries in England and the 3 national registries in Wales, Scotland, and Northern Ireland for the UK statistics.
The organization must wait until all of the data has been published by each country before publishing the figures on the Cancer Research UK website.
Improving hospital-to-home transitions
Photo by Logan Tuttle
Bringing acutely ill children home from the hospital can overwhelm family caregivers and affect a child’s recovery and long-term health, according to a study published in Pediatrics.
Investigators interviewed family caregivers to determine how the hospital-to-home transition affects patients and their families.
The results provided investigators with “family-centered” input that has allowed them to design and test interventions for improving the transition.
The families suggested a need for in-home follow up visits, telephone calls from nurses, enhanced care plans, and other measures.
“Our study finds that transitions from hospital to home affect the lives of families in ways that may impact patient outcomes at discharge,” explained Andrew Beck, MD, of Cincinnati Children’s Hospital in Ohio.
“Many family caregivers expressed mental exhaustion, being in a fog, the emotional toll of having an ill child, and uncertainty on how to care for their child after hospitalization.”
To gain these insights, Dr Beck and his colleagues conducted focus groups and individual interviews with 61 family caregivers.
These individuals were caring for children who had been discharged from the hospital in the preceding 30 days. Eighty-seven percent of participants were female, 46% were nonwhite, 38% were the only adult in the household, and 56% resided in areas with high rates of poverty.
All of the children under care had been discharged from Cincinnati Children’s, a large urban medical center with a diverse patient population.
The investigators conducted a detailed analysis of transcripts from the focus groups and interviews, which revealed 12 different themes of caregiver concerns that fell into 4 overarching concepts:
- “In a fog”—barriers to processing and acting on information
a. mental exhaustion (this is too much)
b. handling uncertainty
c. information overload
d. usability of information
- “What I wish I had”
a. information desired
b. suggested improvements in the discharge process
- “Am I ready to go home?”
a. emotional discharge readiness
b. clinical discharge readiness
- “I’m home, now what?”—having confidence about post-discharge care
a. knowing who to call
b. bridging the gap (desiring a call or nurse home visit)
c. caring for a sick child
d. confidence in caring for a sick child.
“Participants in our study expressed a desire for specific details about worrisome clinical signs or symptoms,” said Lauren Solan, MD, a fellow at Cincinnati Children’s during the study and now a physician at the University of Rochester Medical Center in New York.
“Interventions designed to address informational needs and gaps identified by caregivers may improve feelings of readiness or preparation for transition to the home.”
The current study is part of a multi-stage research project led by Cincinnati Children’s called the Hospital-to-Home Outcomes (H2O) Study, which is focused on improving hospital-to-home transitions for children. This paper zeroed in on obtaining detailed qualitative input from caregivers that would help develop and refine “family-centered” solutions.
In a follow-up study already underway, investigators are testing the effectiveness of nurse follow-up visits in patient homes. The content and structure of these visits have been enhanced based on family input. The investigators are enrolling up to 1500 participants to measure the impact of these visits on hospital readmission rates and outcomes found to be meaningful to families.
Photo by Logan Tuttle
Bringing acutely ill children home from the hospital can overwhelm family caregivers and affect a child’s recovery and long-term health, according to a study published in Pediatrics.
Investigators interviewed family caregivers to determine how the hospital-to-home transition affects patients and their families.
The results provided investigators with “family-centered” input that has allowed them to design and test interventions for improving the transition.
The families suggested a need for in-home follow up visits, telephone calls from nurses, enhanced care plans, and other measures.
“Our study finds that transitions from hospital to home affect the lives of families in ways that may impact patient outcomes at discharge,” explained Andrew Beck, MD, of Cincinnati Children’s Hospital in Ohio.
“Many family caregivers expressed mental exhaustion, being in a fog, the emotional toll of having an ill child, and uncertainty on how to care for their child after hospitalization.”
To gain these insights, Dr Beck and his colleagues conducted focus groups and individual interviews with 61 family caregivers.
These individuals were caring for children who had been discharged from the hospital in the preceding 30 days. Eighty-seven percent of participants were female, 46% were nonwhite, 38% were the only adult in the household, and 56% resided in areas with high rates of poverty.
All of the children under care had been discharged from Cincinnati Children’s, a large urban medical center with a diverse patient population.
The investigators conducted a detailed analysis of transcripts from the focus groups and interviews, which revealed 12 different themes of caregiver concerns that fell into 4 overarching concepts:
- “In a fog”—barriers to processing and acting on information
a. mental exhaustion (this is too much)
b. handling uncertainty
c. information overload
d. usability of information
- “What I wish I had”
a. information desired
b. suggested improvements in the discharge process
- “Am I ready to go home?”
a. emotional discharge readiness
b. clinical discharge readiness
- “I’m home, now what?”—having confidence about post-discharge care
a. knowing who to call
b. bridging the gap (desiring a call or nurse home visit)
c. caring for a sick child
d. confidence in caring for a sick child.
“Participants in our study expressed a desire for specific details about worrisome clinical signs or symptoms,” said Lauren Solan, MD, a fellow at Cincinnati Children’s during the study and now a physician at the University of Rochester Medical Center in New York.
“Interventions designed to address informational needs and gaps identified by caregivers may improve feelings of readiness or preparation for transition to the home.”
The current study is part of a multi-stage research project led by Cincinnati Children’s called the Hospital-to-Home Outcomes (H2O) Study, which is focused on improving hospital-to-home transitions for children. This paper zeroed in on obtaining detailed qualitative input from caregivers that would help develop and refine “family-centered” solutions.
In a follow-up study already underway, investigators are testing the effectiveness of nurse follow-up visits in patient homes. The content and structure of these visits have been enhanced based on family input. The investigators are enrolling up to 1500 participants to measure the impact of these visits on hospital readmission rates and outcomes found to be meaningful to families.
Photo by Logan Tuttle
Bringing acutely ill children home from the hospital can overwhelm family caregivers and affect a child’s recovery and long-term health, according to a study published in Pediatrics.
Investigators interviewed family caregivers to determine how the hospital-to-home transition affects patients and their families.
The results provided investigators with “family-centered” input that has allowed them to design and test interventions for improving the transition.
The families suggested a need for in-home follow up visits, telephone calls from nurses, enhanced care plans, and other measures.
“Our study finds that transitions from hospital to home affect the lives of families in ways that may impact patient outcomes at discharge,” explained Andrew Beck, MD, of Cincinnati Children’s Hospital in Ohio.
“Many family caregivers expressed mental exhaustion, being in a fog, the emotional toll of having an ill child, and uncertainty on how to care for their child after hospitalization.”
To gain these insights, Dr Beck and his colleagues conducted focus groups and individual interviews with 61 family caregivers.
These individuals were caring for children who had been discharged from the hospital in the preceding 30 days. Eighty-seven percent of participants were female, 46% were nonwhite, 38% were the only adult in the household, and 56% resided in areas with high rates of poverty.
All of the children under care had been discharged from Cincinnati Children’s, a large urban medical center with a diverse patient population.
The investigators conducted a detailed analysis of transcripts from the focus groups and interviews, which revealed 12 different themes of caregiver concerns that fell into 4 overarching concepts:
- “In a fog”—barriers to processing and acting on information
a. mental exhaustion (this is too much)
b. handling uncertainty
c. information overload
d. usability of information
- “What I wish I had”
a. information desired
b. suggested improvements in the discharge process
- “Am I ready to go home?”
a. emotional discharge readiness
b. clinical discharge readiness
- “I’m home, now what?”—having confidence about post-discharge care
a. knowing who to call
b. bridging the gap (desiring a call or nurse home visit)
c. caring for a sick child
d. confidence in caring for a sick child.
“Participants in our study expressed a desire for specific details about worrisome clinical signs or symptoms,” said Lauren Solan, MD, a fellow at Cincinnati Children’s during the study and now a physician at the University of Rochester Medical Center in New York.
“Interventions designed to address informational needs and gaps identified by caregivers may improve feelings of readiness or preparation for transition to the home.”
The current study is part of a multi-stage research project led by Cincinnati Children’s called the Hospital-to-Home Outcomes (H2O) Study, which is focused on improving hospital-to-home transitions for children. This paper zeroed in on obtaining detailed qualitative input from caregivers that would help develop and refine “family-centered” solutions.
In a follow-up study already underway, investigators are testing the effectiveness of nurse follow-up visits in patient homes. The content and structure of these visits have been enhanced based on family input. The investigators are enrolling up to 1500 participants to measure the impact of these visits on hospital readmission rates and outcomes found to be meaningful to families.
Activity trackers can monitor HSCT recipients
Activity trackers like the Fitbit can count steps and measure sleep, but a new study suggests they can also be used to gauge patients’ symptoms and overall functional status after hematopoietic stem cell transplant (HSCT).
Researchers used Fitbits to track the physical activity of 32 HSCT recipients and found that decreases in average daily steps were associated with increases in pain, fatigue, and other symptoms, as well as a reduction in self-reported activities.
The researchers say the findings, published in Quality of Life Research, indicate that activity trackers could be a useful tool for tracking symptoms and physical function systematically, especially for patients who may not be able to self-report their symptoms using questionnaires because of language barriers, literacy, or cognitive or health status.
“We found that changes in daily steps are highly correlated with pain and fatigue,” said Antonia Bennett, PhD, of the University of North Carolina at Chapel Hill.
“These wearables provide a way to monitor how patients are doing, and they provide continuous data with very little patient burden.”
For this study, Dr Bennett and her colleagues evaluated daily steps, as measured by Fitbit Flex activity trackers, and symptoms in 32 adults who underwent autologous or allogeneic HSCT to treat leukemia, lymphoma, myeloma, myelodysplastic syndromes, aplastic anemia, or solid tumor malignancy.
The patients wore the activity trackers and completed assessments about their symptoms and quality of life for 4 weeks during transplant hospitalization and 4 weeks after discharge.
Each week, the patients reported symptomatic treatment toxicities using single items from PROCTCAE and symptoms, physical health, mental health, and quality of life using PROMIS_ Global-10. The researchers compared these answers with pedometry data, summarized as average daily steps per week, using linear mixed models.
These analyses showed that decreases in a patient’s average daily steps were associated with increases in the following:
- Pain (852 fewer steps per unit increase in pain score, P<0.001)
- Fatigue (886 fewer steps, P<0.001)
- Vomiting (518 fewer steps, P<0.01)
- Shaking/chills (587 fewer steps, P<0.01)
- Diarrhea (719 fewer steps, P<0.001)
- Shortness of breath (1018 fewer steps, P<0.05)
- Reduction in carrying out social activities (705 fewer steps, P<0.01)
- Reduction in carrying out physical activities (618 fewer steps, P<0.01)
- Global physical health (101 fewer steps, P<0.001).
However, decreases in daily steps were not linked to global mental health or quality of life.
“Studies like this demonstrate that wearable devices can measure an aspect of physical function that is directly related to symptomatic toxicities following treatment,” said William Wood, MD, of the University of North Carolina at Chapel Hill.
“As clinicians, we often want to know–overall, how well are our patients doing with treatment? Are they better, worse, or about the same? Data from wearable devices may allow us to answer these questions with much more precision than we’ve had in the past.”
Activity trackers like the Fitbit can count steps and measure sleep, but a new study suggests they can also be used to gauge patients’ symptoms and overall functional status after hematopoietic stem cell transplant (HSCT).
Researchers used Fitbits to track the physical activity of 32 HSCT recipients and found that decreases in average daily steps were associated with increases in pain, fatigue, and other symptoms, as well as a reduction in self-reported activities.
The researchers say the findings, published in Quality of Life Research, indicate that activity trackers could be a useful tool for tracking symptoms and physical function systematically, especially for patients who may not be able to self-report their symptoms using questionnaires because of language barriers, literacy, or cognitive or health status.
“We found that changes in daily steps are highly correlated with pain and fatigue,” said Antonia Bennett, PhD, of the University of North Carolina at Chapel Hill.
“These wearables provide a way to monitor how patients are doing, and they provide continuous data with very little patient burden.”
For this study, Dr Bennett and her colleagues evaluated daily steps, as measured by Fitbit Flex activity trackers, and symptoms in 32 adults who underwent autologous or allogeneic HSCT to treat leukemia, lymphoma, myeloma, myelodysplastic syndromes, aplastic anemia, or solid tumor malignancy.
The patients wore the activity trackers and completed assessments about their symptoms and quality of life for 4 weeks during transplant hospitalization and 4 weeks after discharge.
Each week, the patients reported symptomatic treatment toxicities using single items from PROCTCAE and symptoms, physical health, mental health, and quality of life using PROMIS_ Global-10. The researchers compared these answers with pedometry data, summarized as average daily steps per week, using linear mixed models.
These analyses showed that decreases in a patient’s average daily steps were associated with increases in the following:
- Pain (852 fewer steps per unit increase in pain score, P<0.001)
- Fatigue (886 fewer steps, P<0.001)
- Vomiting (518 fewer steps, P<0.01)
- Shaking/chills (587 fewer steps, P<0.01)
- Diarrhea (719 fewer steps, P<0.001)
- Shortness of breath (1018 fewer steps, P<0.05)
- Reduction in carrying out social activities (705 fewer steps, P<0.01)
- Reduction in carrying out physical activities (618 fewer steps, P<0.01)
- Global physical health (101 fewer steps, P<0.001).
However, decreases in daily steps were not linked to global mental health or quality of life.
“Studies like this demonstrate that wearable devices can measure an aspect of physical function that is directly related to symptomatic toxicities following treatment,” said William Wood, MD, of the University of North Carolina at Chapel Hill.
“As clinicians, we often want to know–overall, how well are our patients doing with treatment? Are they better, worse, or about the same? Data from wearable devices may allow us to answer these questions with much more precision than we’ve had in the past.”
Activity trackers like the Fitbit can count steps and measure sleep, but a new study suggests they can also be used to gauge patients’ symptoms and overall functional status after hematopoietic stem cell transplant (HSCT).
Researchers used Fitbits to track the physical activity of 32 HSCT recipients and found that decreases in average daily steps were associated with increases in pain, fatigue, and other symptoms, as well as a reduction in self-reported activities.
The researchers say the findings, published in Quality of Life Research, indicate that activity trackers could be a useful tool for tracking symptoms and physical function systematically, especially for patients who may not be able to self-report their symptoms using questionnaires because of language barriers, literacy, or cognitive or health status.
“We found that changes in daily steps are highly correlated with pain and fatigue,” said Antonia Bennett, PhD, of the University of North Carolina at Chapel Hill.
“These wearables provide a way to monitor how patients are doing, and they provide continuous data with very little patient burden.”
For this study, Dr Bennett and her colleagues evaluated daily steps, as measured by Fitbit Flex activity trackers, and symptoms in 32 adults who underwent autologous or allogeneic HSCT to treat leukemia, lymphoma, myeloma, myelodysplastic syndromes, aplastic anemia, or solid tumor malignancy.
The patients wore the activity trackers and completed assessments about their symptoms and quality of life for 4 weeks during transplant hospitalization and 4 weeks after discharge.
Each week, the patients reported symptomatic treatment toxicities using single items from PROCTCAE and symptoms, physical health, mental health, and quality of life using PROMIS_ Global-10. The researchers compared these answers with pedometry data, summarized as average daily steps per week, using linear mixed models.
These analyses showed that decreases in a patient’s average daily steps were associated with increases in the following:
- Pain (852 fewer steps per unit increase in pain score, P<0.001)
- Fatigue (886 fewer steps, P<0.001)
- Vomiting (518 fewer steps, P<0.01)
- Shaking/chills (587 fewer steps, P<0.01)
- Diarrhea (719 fewer steps, P<0.001)
- Shortness of breath (1018 fewer steps, P<0.05)
- Reduction in carrying out social activities (705 fewer steps, P<0.01)
- Reduction in carrying out physical activities (618 fewer steps, P<0.01)
- Global physical health (101 fewer steps, P<0.001).
However, decreases in daily steps were not linked to global mental health or quality of life.
“Studies like this demonstrate that wearable devices can measure an aspect of physical function that is directly related to symptomatic toxicities following treatment,” said William Wood, MD, of the University of North Carolina at Chapel Hill.
“As clinicians, we often want to know–overall, how well are our patients doing with treatment? Are they better, worse, or about the same? Data from wearable devices may allow us to answer these questions with much more precision than we’ve had in the past.”
How a genetic locus protects HSCs
in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.
in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.
in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.