Chromosomes in red

with telomeres in green

Credit: Claus Azzalin

Measuring the length and function of telomeres can help us predict prognosis in patients with chronic lymphocytic leukemia (CLL), according to research published in the British Journal of Haematology.

Investigators found that CLL patients with short, dysfunctional telomeres had a considerably poorer clinical outcome than those with long, functional telomeres.

“For the first time, confident predictions of clinical outcome can be made for individual CLL patients at diagnosis based on accurate analysis of the length of telomeres in cancer cells,” said Chris Pepper, PhD, who led the research at Cardiff University’s School of Medicine in the UK.

“This should prove enormously valuable to doctors, patients, and their families, and there is no reason why there should not be widespread implementation of this powerful prognostic tool in the near future.”

CLL progression is known to be sped up by the loss of telomeres, which cap the ends of chromosomes and protect them from damage when a cell divides. Every time a cell divides, telomeres get shorter.

When they become too short in a healthy cell, signals are sent to instruct the cell to stop dividing and die. But this “safety check” does not occur in CLL cells. Telomeres become so short that chromosomes are left exposed and are prone to fusing together during cell division, causing even larger DNA faults and even greater instability.

So Dr Pepper and his colleagues set out to identify the telomere length at which fusions start to occur in CLL patients.

The team measured telomeres in patient samples using single telomere length analysis (STELA) along with an experimentally derived definition of telomere dysfunction. They defined the upper telomere length threshold at which telomere fusions occur and used the mean of the telomere “fusogenic” range as a prognostic tool.

The researchers first analyzed samples from 200 CLL patients and found that patients with telomeres below the fusogenic mean had significantly shorter overall survival than patients with telomeres above the fusogenic mean (hazard ratio [HR]=13.2, P<0.0001). This was also true for patients with early stage disease (HR=19.3, P<0.0001).

The investigators confirmed this association by analyzing samples from an additional 121 CLL patients. The prognostic impact of telomere dysfunction was evident in the entire cohort (HR=7.4, P<0.0001) and among patients classified as Binet stage A (HR=8.9, P<0.0001).

The researchers also found they could use telomere dysfunction to accurately classify Binet stage A patients into an indolent disease group and a poor prognostic group. At 10 years, the survival rate was 91% in the favorable prognostic group and 13% in the poor prognostic group.

Of note, patients with telomeres above the fusogenic mean had superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. And in a multivariate analysis, the telomere fusogenic mean was associated with the highest hazard of progression and death, independent of all other biomarkers.

“The accuracy of this test in predicting how a person’s disease will develop is unprecedented and, if confirmed in clinical trials, would help doctors decide on the best treatment courses for individual CLL patients,” said Matt Kaiser, PhD, Head of Research at Leukaemia & Lymphoma Research, which funded this study.

“Telomeres are known to play a part in the progress of other forms of cancer, so this type of testing could have far-reaching benefits.”

Chromosomes in red

with telomeres in green

Credit: Claus Azzalin

Measuring the length and function of telomeres can help us predict prognosis in patients with chronic lymphocytic leukemia (CLL), according to research published in the British Journal of Haematology.

Investigators found that CLL patients with short, dysfunctional telomeres had a considerably poorer clinical outcome than those with long, functional telomeres.

“For the first time, confident predictions of clinical outcome can be made for individual CLL patients at diagnosis based on accurate analysis of the length of telomeres in cancer cells,” said Chris Pepper, PhD, who led the research at Cardiff University’s School of Medicine in the UK.

“This should prove enormously valuable to doctors, patients, and their families, and there is no reason why there should not be widespread implementation of this powerful prognostic tool in the near future.”

CLL progression is known to be sped up by the loss of telomeres, which cap the ends of chromosomes and protect them from damage when a cell divides. Every time a cell divides, telomeres get shorter.

When they become too short in a healthy cell, signals are sent to instruct the cell to stop dividing and die. But this “safety check” does not occur in CLL cells. Telomeres become so short that chromosomes are left exposed and are prone to fusing together during cell division, causing even larger DNA faults and even greater instability.

So Dr Pepper and his colleagues set out to identify the telomere length at which fusions start to occur in CLL patients.

The team measured telomeres in patient samples using single telomere length analysis (STELA) along with an experimentally derived definition of telomere dysfunction. They defined the upper telomere length threshold at which telomere fusions occur and used the mean of the telomere “fusogenic” range as a prognostic tool.

The researchers first analyzed samples from 200 CLL patients and found that patients with telomeres below the fusogenic mean had significantly shorter overall survival than patients with telomeres above the fusogenic mean (hazard ratio [HR]=13.2, P<0.0001). This was also true for patients with early stage disease (HR=19.3, P<0.0001).

The investigators confirmed this association by analyzing samples from an additional 121 CLL patients. The prognostic impact of telomere dysfunction was evident in the entire cohort (HR=7.4, P<0.0001) and among patients classified as Binet stage A (HR=8.9, P<0.0001).

The researchers also found they could use telomere dysfunction to accurately classify Binet stage A patients into an indolent disease group and a poor prognostic group. At 10 years, the survival rate was 91% in the favorable prognostic group and 13% in the poor prognostic group.

Of note, patients with telomeres above the fusogenic mean had superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. And in a multivariate analysis, the telomere fusogenic mean was associated with the highest hazard of progression and death, independent of all other biomarkers.

“The accuracy of this test in predicting how a person’s disease will develop is unprecedented and, if confirmed in clinical trials, would help doctors decide on the best treatment courses for individual CLL patients,” said Matt Kaiser, PhD, Head of Research at Leukaemia & Lymphoma Research, which funded this study.

“Telomeres are known to play a part in the progress of other forms of cancer, so this type of testing could have far-reaching benefits.”

Chromosomes in red

with telomeres in green

Credit: Claus Azzalin

Measuring the length and function of telomeres can help us predict prognosis in patients with chronic lymphocytic leukemia (CLL), according to research published in the British Journal of Haematology.

Investigators found that CLL patients with short, dysfunctional telomeres had a considerably poorer clinical outcome than those with long, functional telomeres.

“For the first time, confident predictions of clinical outcome can be made for individual CLL patients at diagnosis based on accurate analysis of the length of telomeres in cancer cells,” said Chris Pepper, PhD, who led the research at Cardiff University’s School of Medicine in the UK.

“This should prove enormously valuable to doctors, patients, and their families, and there is no reason why there should not be widespread implementation of this powerful prognostic tool in the near future.”

CLL progression is known to be sped up by the loss of telomeres, which cap the ends of chromosomes and protect them from damage when a cell divides. Every time a cell divides, telomeres get shorter.

When they become too short in a healthy cell, signals are sent to instruct the cell to stop dividing and die. But this “safety check” does not occur in CLL cells. Telomeres become so short that chromosomes are left exposed and are prone to fusing together during cell division, causing even larger DNA faults and even greater instability.

So Dr Pepper and his colleagues set out to identify the telomere length at which fusions start to occur in CLL patients.

The team measured telomeres in patient samples using single telomere length analysis (STELA) along with an experimentally derived definition of telomere dysfunction. They defined the upper telomere length threshold at which telomere fusions occur and used the mean of the telomere “fusogenic” range as a prognostic tool.

The researchers first analyzed samples from 200 CLL patients and found that patients with telomeres below the fusogenic mean had significantly shorter overall survival than patients with telomeres above the fusogenic mean (hazard ratio [HR]=13.2, P<0.0001). This was also true for patients with early stage disease (HR=19.3, P<0.0001).

The investigators confirmed this association by analyzing samples from an additional 121 CLL patients. The prognostic impact of telomere dysfunction was evident in the entire cohort (HR=7.4, P<0.0001) and among patients classified as Binet stage A (HR=8.9, P<0.0001).

The researchers also found they could use telomere dysfunction to accurately classify Binet stage A patients into an indolent disease group and a poor prognostic group. At 10 years, the survival rate was 91% in the favorable prognostic group and 13% in the poor prognostic group.

Of note, patients with telomeres above the fusogenic mean had superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. And in a multivariate analysis, the telomere fusogenic mean was associated with the highest hazard of progression and death, independent of all other biomarkers.

“The accuracy of this test in predicting how a person’s disease will develop is unprecedented and, if confirmed in clinical trials, would help doctors decide on the best treatment courses for individual CLL patients,” said Matt Kaiser, PhD, Head of Research at Leukaemia & Lymphoma Research, which funded this study.

“Telomeres are known to play a part in the progress of other forms of cancer, so this type of testing could have far-reaching benefits.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Cisplatin crystals

Credit: Larry Ostby

A new formulation of the chemotherapy drug cisplatin can significantly increase the drug’s ability to target and destroy cancer cells, a new study suggests.

Scientists constructed a modified version of cisplatin called Platin-M, which is designed to overcome treatment resistance by attacking mitochondria within cancer cells.

“You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce,” said Shanta Dhar, PhD, of the University of Georgia in Athens, Georgia.

“This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive.”

Dr Dhar and her colleagues described the creation of this prodrug in the Proceedings of the National Academy of Sciences.

Sean Marrache, a graduate student in Dr Dhar’s lab, entrapped Platin-M in a specially designed nanoparticle that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria’s DNA, triggering cell death.

The researchers tested Platin-M on neuroblastoma cells. In experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were roughly 17 times more active than cisplatin alone.

“This technique could become a treatment for a number of cancers, but it may prove most useful for more aggressive forms of cancer that are resistant to current therapies,” said Rakesh Pathak, PhD, a postdoctoral researcher in Dr Dhar’s lab.

However, the researchers cautioned that these results are preliminary, and more work is necessary before Platin-M enters clinical trials. Still, their early results in mouse models are encouraging, and they are currently developing safety trials in larger animals.

“Cisplatin is a well-studied chemotherapy, so we hope our unique formulation will enhance its efficacy,” Dr Dhar said. “We are excited about these early results, which look very promising.”

Cisplatin crystals

Credit: Larry Ostby

A new formulation of the chemotherapy drug cisplatin can significantly increase the drug’s ability to target and destroy cancer cells, a new study suggests.

Scientists constructed a modified version of cisplatin called Platin-M, which is designed to overcome treatment resistance by attacking mitochondria within cancer cells.

“You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce,” said Shanta Dhar, PhD, of the University of Georgia in Athens, Georgia.

“This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive.”

Dr Dhar and her colleagues described the creation of this prodrug in the Proceedings of the National Academy of Sciences.

Sean Marrache, a graduate student in Dr Dhar’s lab, entrapped Platin-M in a specially designed nanoparticle that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria’s DNA, triggering cell death.

The researchers tested Platin-M on neuroblastoma cells. In experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were roughly 17 times more active than cisplatin alone.

“This technique could become a treatment for a number of cancers, but it may prove most useful for more aggressive forms of cancer that are resistant to current therapies,” said Rakesh Pathak, PhD, a postdoctoral researcher in Dr Dhar’s lab.

However, the researchers cautioned that these results are preliminary, and more work is necessary before Platin-M enters clinical trials. Still, their early results in mouse models are encouraging, and they are currently developing safety trials in larger animals.

“Cisplatin is a well-studied chemotherapy, so we hope our unique formulation will enhance its efficacy,” Dr Dhar said. “We are excited about these early results, which look very promising.”

Cisplatin crystals

Credit: Larry Ostby

A new formulation of the chemotherapy drug cisplatin can significantly increase the drug’s ability to target and destroy cancer cells, a new study suggests.

Scientists constructed a modified version of cisplatin called Platin-M, which is designed to overcome treatment resistance by attacking mitochondria within cancer cells.

“You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce,” said Shanta Dhar, PhD, of the University of Georgia in Athens, Georgia.

“This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive.”

Dr Dhar and her colleagues described the creation of this prodrug in the Proceedings of the National Academy of Sciences.

Sean Marrache, a graduate student in Dr Dhar’s lab, entrapped Platin-M in a specially designed nanoparticle that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria’s DNA, triggering cell death.

The researchers tested Platin-M on neuroblastoma cells. In experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were roughly 17 times more active than cisplatin alone.

“This technique could become a treatment for a number of cancers, but it may prove most useful for more aggressive forms of cancer that are resistant to current therapies,” said Rakesh Pathak, PhD, a postdoctoral researcher in Dr Dhar’s lab.

However, the researchers cautioned that these results are preliminary, and more work is necessary before Platin-M enters clinical trials. Still, their early results in mouse models are encouraging, and they are currently developing safety trials in larger animals.

“Cisplatin is a well-studied chemotherapy, so we hope our unique formulation will enhance its efficacy,” Dr Dhar said. “We are excited about these early results, which look very promising.”

For more presentations from the 9th Annual Meeting of the Association of VA Hematology/Oncology (AVAHO), click here: AVAHO Meeting Presentations

For more presentations from the 9th Annual Meeting of the Association of VA Hematology/Oncology (AVAHO), click here: AVAHO Meeting Presentations

For more presentations from the 9th Annual Meeting of the Association of VA Hematology/Oncology (AVAHO), click here: AVAHO Meeting Presentations

Aspergillus fumigatus

T cells modified using the Sleeping Beauty gene transfer system may help fight infections caused by invasive Aspergillus fungus.

Sleeping Beauty is already being used to create chimeric antigen receptor (CAR) T cells to treat leukemias and lymphomas.

And now, researchers have found the system may also be effective for combatting fungal infections that can be deadly for immunosuppressed patients, such as those receiving transplants to treat hematologic cancers.

“We demonstrated a new approach for Aspergillus immunotherapy based on redirecting T-cell specificity through a CAR that recognizes carbohydrate antigen on the fungal cell wall,” said study author Laurence Cooper, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.

He and his colleagues described this approach in the Proceedings of the National Academy of Sciences.

Dr Cooper originally learned about Sleeping Beauty gene transfer from a study published by Perry Hackett, PhD, a professor at the University of Minnesota who created the process.

The system is named Sleeping Beauty because Dr Hackett was able to “awaken” an extinct transposon—DNA that can replicate itself and insert the copy back into the genome—and package it with a gene he wants to transfer into a plasmid. An associated transposase enzyme binds to the plasmid, cuts the transposon and gene out of the plasmid, and pastes it into the target DNA sequence.

Dr Cooper and his colleagues have found they can use this process to engineer T cells that target sugar molecules in the Aspergillus cell walls, thereby killing the fungus.

Specifically, the team adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (D-CAR) upon binding with carbohydrate in the cell wall of Aspergillus germlings. They used Sleeping Beauty to modify the T cells to express D-CAR.

These D-CAR⁺ T cells exhibited specificity for β-glucan, and this inhibited Aspergillus growth both in vitro and in vivo. Furthermore, the researchers found that treating D-CAR⁺ T cells with steroids did not significantly compromise antifungal activity.

“The [D-CAR⁺ T cells] can be manipulated in a manner suitable for human application,” Dr Cooper said, “enabling this immunology to be translated into immunotherapy.”

Aspergillus fumigatus

T cells modified using the Sleeping Beauty gene transfer system may help fight infections caused by invasive Aspergillus fungus.

Sleeping Beauty is already being used to create chimeric antigen receptor (CAR) T cells to treat leukemias and lymphomas.

And now, researchers have found the system may also be effective for combatting fungal infections that can be deadly for immunosuppressed patients, such as those receiving transplants to treat hematologic cancers.

“We demonstrated a new approach for Aspergillus immunotherapy based on redirecting T-cell specificity through a CAR that recognizes carbohydrate antigen on the fungal cell wall,” said study author Laurence Cooper, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.

He and his colleagues described this approach in the Proceedings of the National Academy of Sciences.

Dr Cooper originally learned about Sleeping Beauty gene transfer from a study published by Perry Hackett, PhD, a professor at the University of Minnesota who created the process.

The system is named Sleeping Beauty because Dr Hackett was able to “awaken” an extinct transposon—DNA that can replicate itself and insert the copy back into the genome—and package it with a gene he wants to transfer into a plasmid. An associated transposase enzyme binds to the plasmid, cuts the transposon and gene out of the plasmid, and pastes it into the target DNA sequence.

Dr Cooper and his colleagues have found they can use this process to engineer T cells that target sugar molecules in the Aspergillus cell walls, thereby killing the fungus.

Specifically, the team adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (D-CAR) upon binding with carbohydrate in the cell wall of Aspergillus germlings. They used Sleeping Beauty to modify the T cells to express D-CAR.

These D-CAR⁺ T cells exhibited specificity for β-glucan, and this inhibited Aspergillus growth both in vitro and in vivo. Furthermore, the researchers found that treating D-CAR⁺ T cells with steroids did not significantly compromise antifungal activity.

“The [D-CAR⁺ T cells] can be manipulated in a manner suitable for human application,” Dr Cooper said, “enabling this immunology to be translated into immunotherapy.”

Aspergillus fumigatus

T cells modified using the Sleeping Beauty gene transfer system may help fight infections caused by invasive Aspergillus fungus.

Sleeping Beauty is already being used to create chimeric antigen receptor (CAR) T cells to treat leukemias and lymphomas.

And now, researchers have found the system may also be effective for combatting fungal infections that can be deadly for immunosuppressed patients, such as those receiving transplants to treat hematologic cancers.

“We demonstrated a new approach for Aspergillus immunotherapy based on redirecting T-cell specificity through a CAR that recognizes carbohydrate antigen on the fungal cell wall,” said study author Laurence Cooper, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.

He and his colleagues described this approach in the Proceedings of the National Academy of Sciences.

Dr Cooper originally learned about Sleeping Beauty gene transfer from a study published by Perry Hackett, PhD, a professor at the University of Minnesota who created the process.

The system is named Sleeping Beauty because Dr Hackett was able to “awaken” an extinct transposon—DNA that can replicate itself and insert the copy back into the genome—and package it with a gene he wants to transfer into a plasmid. An associated transposase enzyme binds to the plasmid, cuts the transposon and gene out of the plasmid, and pastes it into the target DNA sequence.

Dr Cooper and his colleagues have found they can use this process to engineer T cells that target sugar molecules in the Aspergillus cell walls, thereby killing the fungus.

Specifically, the team adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (D-CAR) upon binding with carbohydrate in the cell wall of Aspergillus germlings. They used Sleeping Beauty to modify the T cells to express D-CAR.

These D-CAR⁺ T cells exhibited specificity for β-glucan, and this inhibited Aspergillus growth both in vitro and in vivo. Furthermore, the researchers found that treating D-CAR⁺ T cells with steroids did not significantly compromise antifungal activity.

“The [D-CAR⁺ T cells] can be manipulated in a manner suitable for human application,” Dr Cooper said, “enabling this immunology to be translated into immunotherapy.”

Lab mouse

Investigators say they’ve developed nanoparticles that can target multiple myeloma (MM) cells in the bone, as well as increase bone strength and volume to prevent MM progression.

“We engineered and tested a bone-targeted nanoparticle system to selectively target the bone microenvironment and release a therapeutic drug in a spatiotemporally controlled manner, leading to bone microenvironment remodeling and prevention of disease progression,” said study author Archana Swami, PhD, of Brigham and Women’s Hospital in Boston.

She and her colleagues described this system in Proceedings of the National Academy of Sciences.

The team developed stealth nanoparticles made of biodegradable polymers and alendronate, a therapeutic agent that belongs to the bisphosphonate class of drugs. Bisphosphonates bind to calcium and accumulate in high concentration in bones.

By coating the surface of the nanoparticles with alendronate, the investigators enabled the nanoparticles to home to bone tissue to deliver drugs encapsulated within the nanoparticles. In this way, the particles could kill tumor cells and stimulate healthy bone tissue growth.

The investigators tested their drug-toting nanoparticles in mice with MM. The mice were pretreated with nanoparticles containing the drug bortezomib, then injected with MM cells.

The treatment resulted in slower MM growth and prolonged survival. Moreover, bortezomib as a pretreatment regimen changed the make-up of bone, enhancing its strength and volume.

“These findings suggest that bone-targeted nanoparticle anticancer therapies offer a novel way to deliver a concentrated amount of drug in a controlled and target-specific manner to prevent tumor progression in multiple myeloma,” said study author Omid Farokhzad, MD, also of Brigham and Women’s Hospital.

“This approach may prove useful in treatment of incidents of bone metastasis, common in 60% to 80% of cancer patients and for treatment of early stages of multiple myeloma.”

“This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis,” added Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

“This work will pave the way for the development of innovative clinical trials in patients with myeloma to prevent progression from early precursor stages or in patients with breast, prostate, or lung cancer who are at high-risk to develop bone metastasis.”

Lab mouse

Investigators say they’ve developed nanoparticles that can target multiple myeloma (MM) cells in the bone, as well as increase bone strength and volume to prevent MM progression.

“We engineered and tested a bone-targeted nanoparticle system to selectively target the bone microenvironment and release a therapeutic drug in a spatiotemporally controlled manner, leading to bone microenvironment remodeling and prevention of disease progression,” said study author Archana Swami, PhD, of Brigham and Women’s Hospital in Boston.

She and her colleagues described this system in Proceedings of the National Academy of Sciences.

The team developed stealth nanoparticles made of biodegradable polymers and alendronate, a therapeutic agent that belongs to the bisphosphonate class of drugs. Bisphosphonates bind to calcium and accumulate in high concentration in bones.

By coating the surface of the nanoparticles with alendronate, the investigators enabled the nanoparticles to home to bone tissue to deliver drugs encapsulated within the nanoparticles. In this way, the particles could kill tumor cells and stimulate healthy bone tissue growth.

The investigators tested their drug-toting nanoparticles in mice with MM. The mice were pretreated with nanoparticles containing the drug bortezomib, then injected with MM cells.

The treatment resulted in slower MM growth and prolonged survival. Moreover, bortezomib as a pretreatment regimen changed the make-up of bone, enhancing its strength and volume.

“These findings suggest that bone-targeted nanoparticle anticancer therapies offer a novel way to deliver a concentrated amount of drug in a controlled and target-specific manner to prevent tumor progression in multiple myeloma,” said study author Omid Farokhzad, MD, also of Brigham and Women’s Hospital.

“This approach may prove useful in treatment of incidents of bone metastasis, common in 60% to 80% of cancer patients and for treatment of early stages of multiple myeloma.”

“This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis,” added Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

“This work will pave the way for the development of innovative clinical trials in patients with myeloma to prevent progression from early precursor stages or in patients with breast, prostate, or lung cancer who are at high-risk to develop bone metastasis.”

Lab mouse

Investigators say they’ve developed nanoparticles that can target multiple myeloma (MM) cells in the bone, as well as increase bone strength and volume to prevent MM progression.

“We engineered and tested a bone-targeted nanoparticle system to selectively target the bone microenvironment and release a therapeutic drug in a spatiotemporally controlled manner, leading to bone microenvironment remodeling and prevention of disease progression,” said study author Archana Swami, PhD, of Brigham and Women’s Hospital in Boston.

She and her colleagues described this system in Proceedings of the National Academy of Sciences.

The team developed stealth nanoparticles made of biodegradable polymers and alendronate, a therapeutic agent that belongs to the bisphosphonate class of drugs. Bisphosphonates bind to calcium and accumulate in high concentration in bones.

By coating the surface of the nanoparticles with alendronate, the investigators enabled the nanoparticles to home to bone tissue to deliver drugs encapsulated within the nanoparticles. In this way, the particles could kill tumor cells and stimulate healthy bone tissue growth.

The investigators tested their drug-toting nanoparticles in mice with MM. The mice were pretreated with nanoparticles containing the drug bortezomib, then injected with MM cells.

The treatment resulted in slower MM growth and prolonged survival. Moreover, bortezomib as a pretreatment regimen changed the make-up of bone, enhancing its strength and volume.

“These findings suggest that bone-targeted nanoparticle anticancer therapies offer a novel way to deliver a concentrated amount of drug in a controlled and target-specific manner to prevent tumor progression in multiple myeloma,” said study author Omid Farokhzad, MD, also of Brigham and Women’s Hospital.

“This approach may prove useful in treatment of incidents of bone metastasis, common in 60% to 80% of cancer patients and for treatment of early stages of multiple myeloma.”

“This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis,” added Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

“This work will pave the way for the development of innovative clinical trials in patients with myeloma to prevent progression from early precursor stages or in patients with breast, prostate, or lung cancer who are at high-risk to develop bone metastasis.”

Team performing surgery

Credit: Piotr Bodzek

The US Food and Drug Administration (FDA) has approved a recombinant factor VIIa product (NovoSeven® RT) for the treatment of bleeding episodes and for perioperative management in patients with Glanzmann’s Thrombasthenia (GT) who are refractory to platelet transfusions and may or may not have antibodies to platelets.

GT is a rare genetic bleeding disorder with limited treatment options. Patients with GT have a lifelong susceptibility toward bleeding episodes.

The condition, which affects 1 in 1 million people globally, occurs because certain surface proteins on platelets are missing or nonfunctional, significantly impacting the blood’s ability to form strong clots.

Patients with GT typically receive platelet transfusions when experiencing severe bleeding or when undergoing surgical procedures. However, some patients do not respond well, or at all, to platelet transfusions.

The FDA approved NovoSeven® RT for these patients based on evidence collected from the global Glanzmann’s Thrombasthenia Registry and the Hemostasis & Thrombosis Research Society Registry.

The data included 92 GT patients treated with NovoSeven® RT for 266 severe bleeding episodes and 77 GT patients treated with NovoSeven® RT for 160 surgical and other invasive procedures.

The treatment was successful in 94.4% of bleeding episodes and 99.4% of surgical procedures, based on a review of the data by independent hematology experts.

Among 140 patients treated for 518 bleeding episodes, surgeries, or traumatic injuries, the following adverse events were reported: deep vein thrombosis (n=1), headache (n=2), fever (n=2), nausea (n=1), and dyspnea (n=1).

NovoSeven® RT is also approved in the European Union for the treatment of bleeding episodes in patients with GT. The product is marketed by NovoNordisk.

Team performing surgery

Credit: Piotr Bodzek

The US Food and Drug Administration (FDA) has approved a recombinant factor VIIa product (NovoSeven® RT) for the treatment of bleeding episodes and for perioperative management in patients with Glanzmann’s Thrombasthenia (GT) who are refractory to platelet transfusions and may or may not have antibodies to platelets.

GT is a rare genetic bleeding disorder with limited treatment options. Patients with GT have a lifelong susceptibility toward bleeding episodes.

The condition, which affects 1 in 1 million people globally, occurs because certain surface proteins on platelets are missing or nonfunctional, significantly impacting the blood’s ability to form strong clots.

Patients with GT typically receive platelet transfusions when experiencing severe bleeding or when undergoing surgical procedures. However, some patients do not respond well, or at all, to platelet transfusions.

The FDA approved NovoSeven® RT for these patients based on evidence collected from the global Glanzmann’s Thrombasthenia Registry and the Hemostasis & Thrombosis Research Society Registry.

The data included 92 GT patients treated with NovoSeven® RT for 266 severe bleeding episodes and 77 GT patients treated with NovoSeven® RT for 160 surgical and other invasive procedures.

The treatment was successful in 94.4% of bleeding episodes and 99.4% of surgical procedures, based on a review of the data by independent hematology experts.

Among 140 patients treated for 518 bleeding episodes, surgeries, or traumatic injuries, the following adverse events were reported: deep vein thrombosis (n=1), headache (n=2), fever (n=2), nausea (n=1), and dyspnea (n=1).

NovoSeven® RT is also approved in the European Union for the treatment of bleeding episodes in patients with GT. The product is marketed by NovoNordisk.

Team performing surgery

Credit: Piotr Bodzek

The US Food and Drug Administration (FDA) has approved a recombinant factor VIIa product (NovoSeven® RT) for the treatment of bleeding episodes and for perioperative management in patients with Glanzmann’s Thrombasthenia (GT) who are refractory to platelet transfusions and may or may not have antibodies to platelets.

GT is a rare genetic bleeding disorder with limited treatment options. Patients with GT have a lifelong susceptibility toward bleeding episodes.

The condition, which affects 1 in 1 million people globally, occurs because certain surface proteins on platelets are missing or nonfunctional, significantly impacting the blood’s ability to form strong clots.

Patients with GT typically receive platelet transfusions when experiencing severe bleeding or when undergoing surgical procedures. However, some patients do not respond well, or at all, to platelet transfusions.

The FDA approved NovoSeven® RT for these patients based on evidence collected from the global Glanzmann’s Thrombasthenia Registry and the Hemostasis & Thrombosis Research Society Registry.

The data included 92 GT patients treated with NovoSeven® RT for 266 severe bleeding episodes and 77 GT patients treated with NovoSeven® RT for 160 surgical and other invasive procedures.

The treatment was successful in 94.4% of bleeding episodes and 99.4% of surgical procedures, based on a review of the data by independent hematology experts.

Among 140 patients treated for 518 bleeding episodes, surgeries, or traumatic injuries, the following adverse events were reported: deep vein thrombosis (n=1), headache (n=2), fever (n=2), nausea (n=1), and dyspnea (n=1).

NovoSeven® RT is also approved in the European Union for the treatment of bleeding episodes in patients with GT. The product is marketed by NovoNordisk.

Rita Tewari, PhD, in her

lab’s mosquito insectory

The University of Nottingham

A researcher who battled malaria infection as a child is now fighting the disease in her lab and has made a discovery that may bring us closer to successfully disrupting the malaria parasite life-cycle.

Rita Tewari, PhD, of The University of Nottingham in the UK, and her colleagues have completed what she calls a “Herculean study” investigating the roles that 30 protein phosphatases and 72 kinases play as the malaria parasite develops.

Dr Tewari and her colleagues reported the results of this study in Cell Host and Microbe.

“This latest study identifies how protein phosphatases regulate parasite development and differentiation,” she said. “Our research provides a systematic functional analysis for all the 30 phosphatases in Plasmodium berghei, the parasite responsible for causing malaria in rodents.”

“These enzymes work in tandem with the protein kinases identified by the same team in a complementary study carried out in 2010. If we can find out what proteins are essential for these parasites to develop and divide, maybe we can target those proteins and arrest them with drugs or vaccines.”

Born and raised in Delhi, India, Dr Tewari had malaria 7 times as a child. She now leads her own malaria research lab at The University of Nottingham, complete with her own mosquito insectary.

It has taken her team, together with collaborators at Imperial College London, 8 years to identify every one of the protein phosphatases and protein kinases responsible for malaria parasite development.

Protein kinases and phosphatases are crucial for many stages of the malaria parasite lifecycle. And Dr Tewari’s group has been investigating protein kinases and phosphatases to better understand the basic developmental biology of malaria parasites.

Using a number of molecular cell biology and biochemical techniques, the researchers found that 16 of the 30 phosphatase genes they identified could not be knocked out. This suggests some of these genes could be future drug targets, as their presence is critical to parasite growth.

“Interestingly, out of the genes that could be knocked out [14], 6 were found to be crucial for sexual development and, hence, could be drug targets for parasite transmission to and from the mosquito,” Dr Tewari said.

“The research gathered here using the mouse malaria parasite can be directly related to the human malaria parasite, as many of the genes share a very similar homology, and symptoms of the diseases are very similar.”

Rita Tewari, PhD, in her

lab’s mosquito insectory

The University of Nottingham

A researcher who battled malaria infection as a child is now fighting the disease in her lab and has made a discovery that may bring us closer to successfully disrupting the malaria parasite life-cycle.

Rita Tewari, PhD, of The University of Nottingham in the UK, and her colleagues have completed what she calls a “Herculean study” investigating the roles that 30 protein phosphatases and 72 kinases play as the malaria parasite develops.

Dr Tewari and her colleagues reported the results of this study in Cell Host and Microbe.

“This latest study identifies how protein phosphatases regulate parasite development and differentiation,” she said. “Our research provides a systematic functional analysis for all the 30 phosphatases in Plasmodium berghei, the parasite responsible for causing malaria in rodents.”

“These enzymes work in tandem with the protein kinases identified by the same team in a complementary study carried out in 2010. If we can find out what proteins are essential for these parasites to develop and divide, maybe we can target those proteins and arrest them with drugs or vaccines.”

Born and raised in Delhi, India, Dr Tewari had malaria 7 times as a child. She now leads her own malaria research lab at The University of Nottingham, complete with her own mosquito insectary.

It has taken her team, together with collaborators at Imperial College London, 8 years to identify every one of the protein phosphatases and protein kinases responsible for malaria parasite development.

Protein kinases and phosphatases are crucial for many stages of the malaria parasite lifecycle. And Dr Tewari’s group has been investigating protein kinases and phosphatases to better understand the basic developmental biology of malaria parasites.

Using a number of molecular cell biology and biochemical techniques, the researchers found that 16 of the 30 phosphatase genes they identified could not be knocked out. This suggests some of these genes could be future drug targets, as their presence is critical to parasite growth.

“Interestingly, out of the genes that could be knocked out [14], 6 were found to be crucial for sexual development and, hence, could be drug targets for parasite transmission to and from the mosquito,” Dr Tewari said.

“The research gathered here using the mouse malaria parasite can be directly related to the human malaria parasite, as many of the genes share a very similar homology, and symptoms of the diseases are very similar.”

Rita Tewari, PhD, in her

lab’s mosquito insectory

The University of Nottingham

A researcher who battled malaria infection as a child is now fighting the disease in her lab and has made a discovery that may bring us closer to successfully disrupting the malaria parasite life-cycle.

Rita Tewari, PhD, of The University of Nottingham in the UK, and her colleagues have completed what she calls a “Herculean study” investigating the roles that 30 protein phosphatases and 72 kinases play as the malaria parasite develops.

Dr Tewari and her colleagues reported the results of this study in Cell Host and Microbe.

“This latest study identifies how protein phosphatases regulate parasite development and differentiation,” she said. “Our research provides a systematic functional analysis for all the 30 phosphatases in Plasmodium berghei, the parasite responsible for causing malaria in rodents.”

“These enzymes work in tandem with the protein kinases identified by the same team in a complementary study carried out in 2010. If we can find out what proteins are essential for these parasites to develop and divide, maybe we can target those proteins and arrest them with drugs or vaccines.”

Born and raised in Delhi, India, Dr Tewari had malaria 7 times as a child. She now leads her own malaria research lab at The University of Nottingham, complete with her own mosquito insectary.

It has taken her team, together with collaborators at Imperial College London, 8 years to identify every one of the protein phosphatases and protein kinases responsible for malaria parasite development.

Protein kinases and phosphatases are crucial for many stages of the malaria parasite lifecycle. And Dr Tewari’s group has been investigating protein kinases and phosphatases to better understand the basic developmental biology of malaria parasites.

Using a number of molecular cell biology and biochemical techniques, the researchers found that 16 of the 30 phosphatase genes they identified could not be knocked out. This suggests some of these genes could be future drug targets, as their presence is critical to parasite growth.

“Interestingly, out of the genes that could be knocked out [14], 6 were found to be crucial for sexual development and, hence, could be drug targets for parasite transmission to and from the mosquito,” Dr Tewari said.

“The research gathered here using the mouse malaria parasite can be directly related to the human malaria parasite, as many of the genes share a very similar homology, and symptoms of the diseases are very similar.”

CoolSculptingZeltiq Aesthetics, Inc, introduces the CoolSmooth applicator and obtains US Food and Drug Administration clearance for the CoolSculpting procedure to treat the thigh area. The CoolSmooth applicator is designed for fat reduction of the outer thigh. It is a flat applicator that features nonvacuum-based cooling to easily treat nonpinchable fat bulges, offering physicians the ability to optimize patient outcomes and expand CoolSculpting treatment areas. The CoolSculpting procedure previously was cleared for noninvasive fat reduction in the abdomen and flank; now the thigh area (inner and outer thighs) can be treated with the entire suite of applicators. For more information, visit www.coolsculpting.com.

DalvanceDurata Therapeutics, Inc, obtains US Food and Drug Administration approval for Dalvance (dalbavan-cin), an intravenous antibiotic for the treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes. Dalvance is a second-generation semisynthetic lipoglycopeptide. It is administered in a 2-dose regimen of 1000 mg followed 1 week later by 500 mg. Each dose is administered over 30 minutes. Dalvance provides physicians with a treatment option that moves beyond the standard daily or twice-daily intravenous antibiotic infusions. Exercise caution in patients with known hypersensitivity to glycopeptides. For more information, visit www.dalvance.com.

excel HR Laser SystemCutera, Inc, introduces the excel HR laser system for hair removal. excel HR is a dual-wavelength laser system that combines the high-power 755-nm alexandrite and the 1064-nm Nd:YAG with sapphire contact cooling to effectively target deep follicular structures and deliver energy more efficiently. The result is enhanced efficacy using less fluence with improved patient comfort. excel HR has received 510(k) clearance by the US Food and Drug Administration. For more information, visit www.cutera.com/excelhr.

JubliaValeant Pharmaceuticals International, Inc, obtains US Food and Drug Administration approval for Jublia (efinaconazole solution 10%) for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagrophytes. This quick-drying solution is applied daily to the nail with a bottle that has a built-in flow-through brush applicator. There are no concerns for systemic side effects such as drug-drug interactions or acute liver injury. For more information, visit www.jubliarx.com.

SitavigInnocutis launches Sitavig (acyclovir) 50-mg buccal tablets for herpes labialis in the United States. Sitavig uses a proprietary Lauriad delivery system that consists of a tablet that sticks to the patient’s gum, above the canine tooth on the side of the lip that is infected with a cold sore, then dissolves to provide sustained release of medicine. The tablet is tasteless and odorless. Sitavig is user-friendly; patients can eat and drink normally once the tablet adheres to the gum, usually within a few minutes. The application once per episode is unique compared to other systemic and topical treatments. Sitavig is licensed from BioAlliance Pharma. For more information, visit www.innocutis.com.

SivextroCubist Pharmaceuticals announces US Food and Drug Administration approval of Sivextro (tedizolid phosphate) for the treatment of acute bacterial skin and skin structure infections in adults caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. It is available as an intravenous infusion over 1 hour or as a 200-mg tablet administered once daily. Both methods offer an effective 6-day course of therapy. Sivextro allows physicians to transition patients from intravenous to oral treatment; oral administration provides the opportunity for outpatient care. For more information, visit www.sivextro.com.

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

CoolSculptingZeltiq Aesthetics, Inc, introduces the CoolSmooth applicator and obtains US Food and Drug Administration clearance for the CoolSculpting procedure to treat the thigh area. The CoolSmooth applicator is designed for fat reduction of the outer thigh. It is a flat applicator that features nonvacuum-based cooling to easily treat nonpinchable fat bulges, offering physicians the ability to optimize patient outcomes and expand CoolSculpting treatment areas. The CoolSculpting procedure previously was cleared for noninvasive fat reduction in the abdomen and flank; now the thigh area (inner and outer thighs) can be treated with the entire suite of applicators. For more information, visit www.coolsculpting.com.

DalvanceDurata Therapeutics, Inc, obtains US Food and Drug Administration approval for Dalvance (dalbavan-cin), an intravenous antibiotic for the treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes. Dalvance is a second-generation semisynthetic lipoglycopeptide. It is administered in a 2-dose regimen of 1000 mg followed 1 week later by 500 mg. Each dose is administered over 30 minutes. Dalvance provides physicians with a treatment option that moves beyond the standard daily or twice-daily intravenous antibiotic infusions. Exercise caution in patients with known hypersensitivity to glycopeptides. For more information, visit www.dalvance.com.

excel HR Laser SystemCutera, Inc, introduces the excel HR laser system for hair removal. excel HR is a dual-wavelength laser system that combines the high-power 755-nm alexandrite and the 1064-nm Nd:YAG with sapphire contact cooling to effectively target deep follicular structures and deliver energy more efficiently. The result is enhanced efficacy using less fluence with improved patient comfort. excel HR has received 510(k) clearance by the US Food and Drug Administration. For more information, visit www.cutera.com/excelhr.

JubliaValeant Pharmaceuticals International, Inc, obtains US Food and Drug Administration approval for Jublia (efinaconazole solution 10%) for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagrophytes. This quick-drying solution is applied daily to the nail with a bottle that has a built-in flow-through brush applicator. There are no concerns for systemic side effects such as drug-drug interactions or acute liver injury. For more information, visit www.jubliarx.com.

SitavigInnocutis launches Sitavig (acyclovir) 50-mg buccal tablets for herpes labialis in the United States. Sitavig uses a proprietary Lauriad delivery system that consists of a tablet that sticks to the patient’s gum, above the canine tooth on the side of the lip that is infected with a cold sore, then dissolves to provide sustained release of medicine. The tablet is tasteless and odorless. Sitavig is user-friendly; patients can eat and drink normally once the tablet adheres to the gum, usually within a few minutes. The application once per episode is unique compared to other systemic and topical treatments. Sitavig is licensed from BioAlliance Pharma. For more information, visit www.innocutis.com.

SivextroCubist Pharmaceuticals announces US Food and Drug Administration approval of Sivextro (tedizolid phosphate) for the treatment of acute bacterial skin and skin structure infections in adults caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. It is available as an intravenous infusion over 1 hour or as a 200-mg tablet administered once daily. Both methods offer an effective 6-day course of therapy. Sivextro allows physicians to transition patients from intravenous to oral treatment; oral administration provides the opportunity for outpatient care. For more information, visit www.sivextro.com.

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

CoolSculptingZeltiq Aesthetics, Inc, introduces the CoolSmooth applicator and obtains US Food and Drug Administration clearance for the CoolSculpting procedure to treat the thigh area. The CoolSmooth applicator is designed for fat reduction of the outer thigh. It is a flat applicator that features nonvacuum-based cooling to easily treat nonpinchable fat bulges, offering physicians the ability to optimize patient outcomes and expand CoolSculpting treatment areas. The CoolSculpting procedure previously was cleared for noninvasive fat reduction in the abdomen and flank; now the thigh area (inner and outer thighs) can be treated with the entire suite of applicators. For more information, visit www.coolsculpting.com.

DalvanceDurata Therapeutics, Inc, obtains US Food and Drug Administration approval for Dalvance (dalbavan-cin), an intravenous antibiotic for the treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes. Dalvance is a second-generation semisynthetic lipoglycopeptide. It is administered in a 2-dose regimen of 1000 mg followed 1 week later by 500 mg. Each dose is administered over 30 minutes. Dalvance provides physicians with a treatment option that moves beyond the standard daily or twice-daily intravenous antibiotic infusions. Exercise caution in patients with known hypersensitivity to glycopeptides. For more information, visit www.dalvance.com.

excel HR Laser SystemCutera, Inc, introduces the excel HR laser system for hair removal. excel HR is a dual-wavelength laser system that combines the high-power 755-nm alexandrite and the 1064-nm Nd:YAG with sapphire contact cooling to effectively target deep follicular structures and deliver energy more efficiently. The result is enhanced efficacy using less fluence with improved patient comfort. excel HR has received 510(k) clearance by the US Food and Drug Administration. For more information, visit www.cutera.com/excelhr.

JubliaValeant Pharmaceuticals International, Inc, obtains US Food and Drug Administration approval for Jublia (efinaconazole solution 10%) for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagrophytes. This quick-drying solution is applied daily to the nail with a bottle that has a built-in flow-through brush applicator. There are no concerns for systemic side effects such as drug-drug interactions or acute liver injury. For more information, visit www.jubliarx.com.

SitavigInnocutis launches Sitavig (acyclovir) 50-mg buccal tablets for herpes labialis in the United States. Sitavig uses a proprietary Lauriad delivery system that consists of a tablet that sticks to the patient’s gum, above the canine tooth on the side of the lip that is infected with a cold sore, then dissolves to provide sustained release of medicine. The tablet is tasteless and odorless. Sitavig is user-friendly; patients can eat and drink normally once the tablet adheres to the gum, usually within a few minutes. The application once per episode is unique compared to other systemic and topical treatments. Sitavig is licensed from BioAlliance Pharma. For more information, visit www.innocutis.com.

SivextroCubist Pharmaceuticals announces US Food and Drug Administration approval of Sivextro (tedizolid phosphate) for the treatment of acute bacterial skin and skin structure infections in adults caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. It is available as an intravenous infusion over 1 hour or as a 200-mg tablet administered once daily. Both methods offer an effective 6-day course of therapy. Sivextro allows physicians to transition patients from intravenous to oral treatment; oral administration provides the opportunity for outpatient care. For more information, visit www.sivextro.com.

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

In an era where everything around us has moved toward an "I need it now and I need it fast" attitude, the face of medicine also has changed. The days of patients wanting to wait to see their physician have faded, and now there is a demand for a quick fix so they can keep their already hectic lives moving.

Retail clinics also have thrown a curve ball to practicing physicians because now patients can get their fast medicine right along with their fast food, all at the corner strip mall.

The Internet also has changed how office visits run. Now physicians spend a lot of time explaining diagnoses that patients have found during their exhaustive research of their symptoms, or dispelling erroneous information that has been found on the Internet. This adds to time per patient, as well as distrust. Patients are now smarter, busier, and more likely to have chronic illnesses, so how does medicine keep up with the times?

As physicians, we must remember that our expertise as medical doctors is to rule in and rule out serious diseases. The "bread and butter" of any medical practice is likely easy to identify and treat, but where the expertise comes in is how to distinguish minor acute illness from life-threatening or potentially chronic illness. Many disease states are efficiently diagnosed only because the patient presents with further complaints that put the entire picture together. How is that achieved when patients fast-track through "minute clinics"?

Experience is also golden. If you have practiced long enough, you have had your share of surprises and know that "oh, it’s nothing" is the diagnosis only after all the "somethings " have been ruled out. For example, in adolescent medicine I commonly get the complaints of abdominal pain and anxiety. So when a patient presents with ongoing complaints of abdominal pain with no other clinical signs of disease, there is a temptation to assume it is just the anxiety. But experience teaches you that viral hepatitis, appendicitis, or urological disorders could be the underlying problem.

Another lesson that is taught by experience is how children express themselves. I recently saw an adolescent who had a minor trauma where he was struck in the chest with a basketball. He subsequently complained of chest pain, but kept saying, "I feel like I’m going to die." His mother was insistent that this was just his already diagnosed anxiety, and that he would settle down. But stating he "felt like he was going to die" was such an unusual complaint for a child that I was prompted to do an EKG, which revealed a viral myocarditis. Although this may have been identified in an express clinic, knowing the patient helped in expediting the diagnosis.

As physicians, we must educate and ensure that our patients feel they are getting the best care by sticking with someone who knows them. We have to accept that patients have options, so if we are going to keep their business, we have to work more efficiently, form relationships, and provide good care. Many practices have moved toward a concierge service, where a fee is charged for immediate appointments or telephone access. Utilization of a nurse practitioner can allow you to run your office more efficiently to manage the more acute illnesses, shorten the wait times, and maximize patient visits.

Retail clinics are here to stay. If we are going to keep private practices afloat, we have to make the visit worth the wait!

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

In an era where everything around us has moved toward an "I need it now and I need it fast" attitude, the face of medicine also has changed. The days of patients wanting to wait to see their physician have faded, and now there is a demand for a quick fix so they can keep their already hectic lives moving.

Retail clinics also have thrown a curve ball to practicing physicians because now patients can get their fast medicine right along with their fast food, all at the corner strip mall.

The Internet also has changed how office visits run. Now physicians spend a lot of time explaining diagnoses that patients have found during their exhaustive research of their symptoms, or dispelling erroneous information that has been found on the Internet. This adds to time per patient, as well as distrust. Patients are now smarter, busier, and more likely to have chronic illnesses, so how does medicine keep up with the times?

As physicians, we must remember that our expertise as medical doctors is to rule in and rule out serious diseases. The "bread and butter" of any medical practice is likely easy to identify and treat, but where the expertise comes in is how to distinguish minor acute illness from life-threatening or potentially chronic illness. Many disease states are efficiently diagnosed only because the patient presents with further complaints that put the entire picture together. How is that achieved when patients fast-track through "minute clinics"?

Experience is also golden. If you have practiced long enough, you have had your share of surprises and know that "oh, it’s nothing" is the diagnosis only after all the "somethings " have been ruled out. For example, in adolescent medicine I commonly get the complaints of abdominal pain and anxiety. So when a patient presents with ongoing complaints of abdominal pain with no other clinical signs of disease, there is a temptation to assume it is just the anxiety. But experience teaches you that viral hepatitis, appendicitis, or urological disorders could be the underlying problem.

Another lesson that is taught by experience is how children express themselves. I recently saw an adolescent who had a minor trauma where he was struck in the chest with a basketball. He subsequently complained of chest pain, but kept saying, "I feel like I’m going to die." His mother was insistent that this was just his already diagnosed anxiety, and that he would settle down. But stating he "felt like he was going to die" was such an unusual complaint for a child that I was prompted to do an EKG, which revealed a viral myocarditis. Although this may have been identified in an express clinic, knowing the patient helped in expediting the diagnosis.

As physicians, we must educate and ensure that our patients feel they are getting the best care by sticking with someone who knows them. We have to accept that patients have options, so if we are going to keep their business, we have to work more efficiently, form relationships, and provide good care. Many practices have moved toward a concierge service, where a fee is charged for immediate appointments or telephone access. Utilization of a nurse practitioner can allow you to run your office more efficiently to manage the more acute illnesses, shorten the wait times, and maximize patient visits.

Retail clinics are here to stay. If we are going to keep private practices afloat, we have to make the visit worth the wait!

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

In an era where everything around us has moved toward an "I need it now and I need it fast" attitude, the face of medicine also has changed. The days of patients wanting to wait to see their physician have faded, and now there is a demand for a quick fix so they can keep their already hectic lives moving.

Retail clinics also have thrown a curve ball to practicing physicians because now patients can get their fast medicine right along with their fast food, all at the corner strip mall.

The Internet also has changed how office visits run. Now physicians spend a lot of time explaining diagnoses that patients have found during their exhaustive research of their symptoms, or dispelling erroneous information that has been found on the Internet. This adds to time per patient, as well as distrust. Patients are now smarter, busier, and more likely to have chronic illnesses, so how does medicine keep up with the times?

As physicians, we must remember that our expertise as medical doctors is to rule in and rule out serious diseases. The "bread and butter" of any medical practice is likely easy to identify and treat, but where the expertise comes in is how to distinguish minor acute illness from life-threatening or potentially chronic illness. Many disease states are efficiently diagnosed only because the patient presents with further complaints that put the entire picture together. How is that achieved when patients fast-track through "minute clinics"?

Experience is also golden. If you have practiced long enough, you have had your share of surprises and know that "oh, it’s nothing" is the diagnosis only after all the "somethings " have been ruled out. For example, in adolescent medicine I commonly get the complaints of abdominal pain and anxiety. So when a patient presents with ongoing complaints of abdominal pain with no other clinical signs of disease, there is a temptation to assume it is just the anxiety. But experience teaches you that viral hepatitis, appendicitis, or urological disorders could be the underlying problem.

Another lesson that is taught by experience is how children express themselves. I recently saw an adolescent who had a minor trauma where he was struck in the chest with a basketball. He subsequently complained of chest pain, but kept saying, "I feel like I’m going to die." His mother was insistent that this was just his already diagnosed anxiety, and that he would settle down. But stating he "felt like he was going to die" was such an unusual complaint for a child that I was prompted to do an EKG, which revealed a viral myocarditis. Although this may have been identified in an express clinic, knowing the patient helped in expediting the diagnosis.

As physicians, we must educate and ensure that our patients feel they are getting the best care by sticking with someone who knows them. We have to accept that patients have options, so if we are going to keep their business, we have to work more efficiently, form relationships, and provide good care. Many practices have moved toward a concierge service, where a fee is charged for immediate appointments or telephone access. Utilization of a nurse practitioner can allow you to run your office more efficiently to manage the more acute illnesses, shorten the wait times, and maximize patient visits.

Retail clinics are here to stay. If we are going to keep private practices afloat, we have to make the visit worth the wait!

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].