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Circadian disruption negatively affects RBCs
Credit: NHLBI
MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.
The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.
And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.
This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.
The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.
The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.
Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.
“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.
Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.
They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.
However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.
The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.
“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.
“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”
Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system. 
Credit: NHLBI
MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.
The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.
And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.
This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.
The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.
The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.
Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.
“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.
Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.
They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.
However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.
The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.
“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.
“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”
Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system.
Credit: NHLBI
MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.
The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.
And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.
This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.
The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.
The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.
Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.
“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.
Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.
They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.
However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.
The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.
“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.
“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”
Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system.
Inhibitor gets accelerated approval for PTCL
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.
New compound blocks essential enzyme
Credit: Peter H. Seeberger
A novel compound can inhibit an enzyme that is essential for malaria parasite survival, according to research published in PLOS Biology.
Researchers believe that creating this compound, WEHI-916, is the first step toward developing a new class of antimalarial drugs that could cure and prevent malaria infections caused by all species of the parasite, including those resistant to existing drugs.
The group developed WEHI-916 to block the enzyme Plasmepsin V. They previously showed Plasmepsin V is responsible for controlling the transport of proteins in and out of the malaria parasite.
Now, they’ve used WEHI-916 to prove the importance of Plasmepsin V to the survival of both Plasmodium vivax and Plasmodium falciparum.
“Researchers, including us, had been trying, without success, to learn more about Plasmepsin V using standard genetic techniques,” said study author Just Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
“Our idea was to create a drug-like compound that would block Plasmepsin V so we could investigate its importance. We found that blocking Plasmepsin V kills malaria parasites and delivered a new and effective potential drug at the same time.”
Plasmepsin V was an ideal drug target because its inhibition effectively halted the transport of hundreds of malaria proteins, Dr Boddey noted.
“The Plasmodium parasite needs to produce and deliver over 300 different proteins to the red blood cell to survive in the body and hide from the host’s immune system,” he said. “Instead of targeting individual proteins, we can block Plasmepsin V and prevent all of those proteins from leaving the parasite.”
The researchers believe these findings could aid the development of drugs that are effective in curing malaria caused by all 5 species of Plasmodium parasite.
“Our study has shown that Plasmepsin V is a key enzyme in [P vivax and P falciparum], and WEHI-916 can inhibit Plasmepsin V isolated from both of them,” said study author Brad Sleebs, PhD, also of The Walter and Eliza Hall Institute.
“Not only does this compound enable us to prove Plasmepsin V is an excellent drug target, it is a starting point for a research program that could lead to a new class of antimalarial drugs.”
Now, the researchers have turned their attention to developing WEHI-916 and related compounds for human use.
“We are now examining in our insectary whether Plasmepsin V could be a target during other stages of the malaria lifecycle,” Dr Boddey said. “The enzyme is present in the parasites that first infect humans in the liver, as well as in parasite forms that exit humans and infect mosquitoes.”
“If WEHI-916 kills the parasite during these stages as well, it will mean any drugs that target Plasmepsin V can be used as a preventative as well as a cure.”
Credit: Peter H. Seeberger
A novel compound can inhibit an enzyme that is essential for malaria parasite survival, according to research published in PLOS Biology.
Researchers believe that creating this compound, WEHI-916, is the first step toward developing a new class of antimalarial drugs that could cure and prevent malaria infections caused by all species of the parasite, including those resistant to existing drugs.
The group developed WEHI-916 to block the enzyme Plasmepsin V. They previously showed Plasmepsin V is responsible for controlling the transport of proteins in and out of the malaria parasite.
Now, they’ve used WEHI-916 to prove the importance of Plasmepsin V to the survival of both Plasmodium vivax and Plasmodium falciparum.
“Researchers, including us, had been trying, without success, to learn more about Plasmepsin V using standard genetic techniques,” said study author Just Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
“Our idea was to create a drug-like compound that would block Plasmepsin V so we could investigate its importance. We found that blocking Plasmepsin V kills malaria parasites and delivered a new and effective potential drug at the same time.”
Plasmepsin V was an ideal drug target because its inhibition effectively halted the transport of hundreds of malaria proteins, Dr Boddey noted.
“The Plasmodium parasite needs to produce and deliver over 300 different proteins to the red blood cell to survive in the body and hide from the host’s immune system,” he said. “Instead of targeting individual proteins, we can block Plasmepsin V and prevent all of those proteins from leaving the parasite.”
The researchers believe these findings could aid the development of drugs that are effective in curing malaria caused by all 5 species of Plasmodium parasite.
“Our study has shown that Plasmepsin V is a key enzyme in [P vivax and P falciparum], and WEHI-916 can inhibit Plasmepsin V isolated from both of them,” said study author Brad Sleebs, PhD, also of The Walter and Eliza Hall Institute.
“Not only does this compound enable us to prove Plasmepsin V is an excellent drug target, it is a starting point for a research program that could lead to a new class of antimalarial drugs.”
Now, the researchers have turned their attention to developing WEHI-916 and related compounds for human use.
“We are now examining in our insectary whether Plasmepsin V could be a target during other stages of the malaria lifecycle,” Dr Boddey said. “The enzyme is present in the parasites that first infect humans in the liver, as well as in parasite forms that exit humans and infect mosquitoes.”
“If WEHI-916 kills the parasite during these stages as well, it will mean any drugs that target Plasmepsin V can be used as a preventative as well as a cure.”
Credit: Peter H. Seeberger
A novel compound can inhibit an enzyme that is essential for malaria parasite survival, according to research published in PLOS Biology.
Researchers believe that creating this compound, WEHI-916, is the first step toward developing a new class of antimalarial drugs that could cure and prevent malaria infections caused by all species of the parasite, including those resistant to existing drugs.
The group developed WEHI-916 to block the enzyme Plasmepsin V. They previously showed Plasmepsin V is responsible for controlling the transport of proteins in and out of the malaria parasite.
Now, they’ve used WEHI-916 to prove the importance of Plasmepsin V to the survival of both Plasmodium vivax and Plasmodium falciparum.
“Researchers, including us, had been trying, without success, to learn more about Plasmepsin V using standard genetic techniques,” said study author Just Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
“Our idea was to create a drug-like compound that would block Plasmepsin V so we could investigate its importance. We found that blocking Plasmepsin V kills malaria parasites and delivered a new and effective potential drug at the same time.”
Plasmepsin V was an ideal drug target because its inhibition effectively halted the transport of hundreds of malaria proteins, Dr Boddey noted.
“The Plasmodium parasite needs to produce and deliver over 300 different proteins to the red blood cell to survive in the body and hide from the host’s immune system,” he said. “Instead of targeting individual proteins, we can block Plasmepsin V and prevent all of those proteins from leaving the parasite.”
The researchers believe these findings could aid the development of drugs that are effective in curing malaria caused by all 5 species of Plasmodium parasite.
“Our study has shown that Plasmepsin V is a key enzyme in [P vivax and P falciparum], and WEHI-916 can inhibit Plasmepsin V isolated from both of them,” said study author Brad Sleebs, PhD, also of The Walter and Eliza Hall Institute.
“Not only does this compound enable us to prove Plasmepsin V is an excellent drug target, it is a starting point for a research program that could lead to a new class of antimalarial drugs.”
Now, the researchers have turned their attention to developing WEHI-916 and related compounds for human use.
“We are now examining in our insectary whether Plasmepsin V could be a target during other stages of the malaria lifecycle,” Dr Boddey said. “The enzyme is present in the parasites that first infect humans in the liver, as well as in parasite forms that exit humans and infect mosquitoes.”
“If WEHI-916 kills the parasite during these stages as well, it will mean any drugs that target Plasmepsin V can be used as a preventative as well as a cure.”
Unsuspected aspect of immune regulation revealed
Immunologists may have discovered an additional role for B cells. Their research suggests the cells participate in the development of regulatory T cells (Tregs).
Until now, the only non-thymic cells known to aid Treg production were dendritic cells, which travel to the thymus to deliver antigens.
The new research, published in the Journal of Immunology, suggests B cells can do the same thing.
B cells were previously thought to specialize only in antibody production. With their newly discovered role, the cells become much more interesting and complex characters, according to the researchers.
The findings mean B cells could have useful applications for treating transplant patients and those with autoimmune disorders.
“Regulatory T cells are critical in the outcome of an immune response, so anything that regulates them becomes very interesting to immunologists,” said study author Shane Grey, PhD, of the Garvan Institute of Medical Research in Darlinghurst, New South Wales, Australia.
“Right now, there are clinical trials around the world looking to expand populations of these cells in patients. Researchers are also working on ways to grow regulatory cells in the laboratory—to infuse into patients as therapy. Our finding suggests it should be possible to set up systems that harness B cells to expand regulatory cells.”
Dr Grey and his colleagues worked with mice genetically modified to express high levels of BAFF, which increases B-cell survival. The higher number of B cells overall allowed researchers to track the activity of B cells in the thymus.
“It has been known for years that some B cells travel to the thymus, but no one has understood why,” said study author Stacey Walters, also of the Garvan Institute of Medical Research.
“Our experiments showed clearly that B cells participated in the creation of regulatory T cells. The more B cells that were in the thymus, the higher the number of regulatory cells generated. That direct correlation raises interesting possibilities. One possibility is using BAFF, a non-toxic substance, to ramp up the B-cell count of patients before transplant procedures.”
Research has suggested that Tregs can reduce the risk of graft-vs-host disease, promote enhanced immune reconstitution, and decrease the incidence of infectious complications in stem cell transplant recipients. And several studies have shown that high levels of Tregs can prevent graft rejection after solid organ transplant.
Immunologists may have discovered an additional role for B cells. Their research suggests the cells participate in the development of regulatory T cells (Tregs).
Until now, the only non-thymic cells known to aid Treg production were dendritic cells, which travel to the thymus to deliver antigens.
The new research, published in the Journal of Immunology, suggests B cells can do the same thing.
B cells were previously thought to specialize only in antibody production. With their newly discovered role, the cells become much more interesting and complex characters, according to the researchers.
The findings mean B cells could have useful applications for treating transplant patients and those with autoimmune disorders.
“Regulatory T cells are critical in the outcome of an immune response, so anything that regulates them becomes very interesting to immunologists,” said study author Shane Grey, PhD, of the Garvan Institute of Medical Research in Darlinghurst, New South Wales, Australia.
“Right now, there are clinical trials around the world looking to expand populations of these cells in patients. Researchers are also working on ways to grow regulatory cells in the laboratory—to infuse into patients as therapy. Our finding suggests it should be possible to set up systems that harness B cells to expand regulatory cells.”
Dr Grey and his colleagues worked with mice genetically modified to express high levels of BAFF, which increases B-cell survival. The higher number of B cells overall allowed researchers to track the activity of B cells in the thymus.
“It has been known for years that some B cells travel to the thymus, but no one has understood why,” said study author Stacey Walters, also of the Garvan Institute of Medical Research.
“Our experiments showed clearly that B cells participated in the creation of regulatory T cells. The more B cells that were in the thymus, the higher the number of regulatory cells generated. That direct correlation raises interesting possibilities. One possibility is using BAFF, a non-toxic substance, to ramp up the B-cell count of patients before transplant procedures.”
Research has suggested that Tregs can reduce the risk of graft-vs-host disease, promote enhanced immune reconstitution, and decrease the incidence of infectious complications in stem cell transplant recipients. And several studies have shown that high levels of Tregs can prevent graft rejection after solid organ transplant.
Immunologists may have discovered an additional role for B cells. Their research suggests the cells participate in the development of regulatory T cells (Tregs).
Until now, the only non-thymic cells known to aid Treg production were dendritic cells, which travel to the thymus to deliver antigens.
The new research, published in the Journal of Immunology, suggests B cells can do the same thing.
B cells were previously thought to specialize only in antibody production. With their newly discovered role, the cells become much more interesting and complex characters, according to the researchers.
The findings mean B cells could have useful applications for treating transplant patients and those with autoimmune disorders.
“Regulatory T cells are critical in the outcome of an immune response, so anything that regulates them becomes very interesting to immunologists,” said study author Shane Grey, PhD, of the Garvan Institute of Medical Research in Darlinghurst, New South Wales, Australia.
“Right now, there are clinical trials around the world looking to expand populations of these cells in patients. Researchers are also working on ways to grow regulatory cells in the laboratory—to infuse into patients as therapy. Our finding suggests it should be possible to set up systems that harness B cells to expand regulatory cells.”
Dr Grey and his colleagues worked with mice genetically modified to express high levels of BAFF, which increases B-cell survival. The higher number of B cells overall allowed researchers to track the activity of B cells in the thymus.
“It has been known for years that some B cells travel to the thymus, but no one has understood why,” said study author Stacey Walters, also of the Garvan Institute of Medical Research.
“Our experiments showed clearly that B cells participated in the creation of regulatory T cells. The more B cells that were in the thymus, the higher the number of regulatory cells generated. That direct correlation raises interesting possibilities. One possibility is using BAFF, a non-toxic substance, to ramp up the B-cell count of patients before transplant procedures.”
Research has suggested that Tregs can reduce the risk of graft-vs-host disease, promote enhanced immune reconstitution, and decrease the incidence of infectious complications in stem cell transplant recipients. And several studies have shown that high levels of Tregs can prevent graft rejection after solid organ transplant.
Mixing meds and supplements to dangerous effect
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
FISH may help predict survival in ALCL
Researchers have discovered 3 subgroups of ALK-negative anaplastic large-cell lymphoma (ALCL) that have markedly different survival rates, according to a paper published in Blood.
They found that ALCL patients with TP63 rearrangements had a 17% chance of living 5 years beyond diagnosis, compared to 90% of patients who had DUSP22 rearrangements.
A third group of patients, those with neither rearrangement, had a 42% survival rate.
The researchers noted that these subgroups cannot be differentiated by routine pathology but can be identified via fluorescence in situ hybridization (FISH).
“This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,” said study author Andrew L. Feldman, MD, of the Mayo Clinic in Rochester, Minnesota.
“Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.”
Currently, all ALK-negative ALCLs are treated the same, using chemotherapy and, in some institutions, stem cell transplantation. But these new findings make a case for additional testing and possible changes to the standard of care.
“This is a great example of where individualized medicine can make a difference,” Dr Feldman said. “Patients whose chance of surviving is 1 in 6 are receiving the same therapy as patients whose odds are 9 in 10. Developing tests that identify how tumors are different is a critical step toward being able to tailor therapy to each individual patient.”
Therefore, Dr Feldman and his colleagues recommend performing FISH in all patients with ALK-negative ALCL.
To learn more about testing for DUSP22 and TP63:
- 6p25.3 FISH (DUSP22/IRF4): http://www.mayomedicallaboratories.com/test-catalog/Overview/60506
- 3q28 FISH (TP63): http://www.mayomedicallaboratories.com/test-catalog/Overview/70014.
Researchers have discovered 3 subgroups of ALK-negative anaplastic large-cell lymphoma (ALCL) that have markedly different survival rates, according to a paper published in Blood.
They found that ALCL patients with TP63 rearrangements had a 17% chance of living 5 years beyond diagnosis, compared to 90% of patients who had DUSP22 rearrangements.
A third group of patients, those with neither rearrangement, had a 42% survival rate.
The researchers noted that these subgroups cannot be differentiated by routine pathology but can be identified via fluorescence in situ hybridization (FISH).
“This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,” said study author Andrew L. Feldman, MD, of the Mayo Clinic in Rochester, Minnesota.
“Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.”
Currently, all ALK-negative ALCLs are treated the same, using chemotherapy and, in some institutions, stem cell transplantation. But these new findings make a case for additional testing and possible changes to the standard of care.
“This is a great example of where individualized medicine can make a difference,” Dr Feldman said. “Patients whose chance of surviving is 1 in 6 are receiving the same therapy as patients whose odds are 9 in 10. Developing tests that identify how tumors are different is a critical step toward being able to tailor therapy to each individual patient.”
Therefore, Dr Feldman and his colleagues recommend performing FISH in all patients with ALK-negative ALCL.
To learn more about testing for DUSP22 and TP63:
- 6p25.3 FISH (DUSP22/IRF4): http://www.mayomedicallaboratories.com/test-catalog/Overview/60506
- 3q28 FISH (TP63): http://www.mayomedicallaboratories.com/test-catalog/Overview/70014.
Researchers have discovered 3 subgroups of ALK-negative anaplastic large-cell lymphoma (ALCL) that have markedly different survival rates, according to a paper published in Blood.
They found that ALCL patients with TP63 rearrangements had a 17% chance of living 5 years beyond diagnosis, compared to 90% of patients who had DUSP22 rearrangements.
A third group of patients, those with neither rearrangement, had a 42% survival rate.
The researchers noted that these subgroups cannot be differentiated by routine pathology but can be identified via fluorescence in situ hybridization (FISH).
“This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,” said study author Andrew L. Feldman, MD, of the Mayo Clinic in Rochester, Minnesota.
“Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.”
Currently, all ALK-negative ALCLs are treated the same, using chemotherapy and, in some institutions, stem cell transplantation. But these new findings make a case for additional testing and possible changes to the standard of care.
“This is a great example of where individualized medicine can make a difference,” Dr Feldman said. “Patients whose chance of surviving is 1 in 6 are receiving the same therapy as patients whose odds are 9 in 10. Developing tests that identify how tumors are different is a critical step toward being able to tailor therapy to each individual patient.”
Therefore, Dr Feldman and his colleagues recommend performing FISH in all patients with ALK-negative ALCL.
To learn more about testing for DUSP22 and TP63:
- 6p25.3 FISH (DUSP22/IRF4): http://www.mayomedicallaboratories.com/test-catalog/Overview/60506
- 3q28 FISH (TP63): http://www.mayomedicallaboratories.com/test-catalog/Overview/70014.
Mosquitos can sniff out malaria-infected mice
Credit: James Gathany
Scientists have found evidence to suggest that malaria parasites change the body odor of their host to attract hungry mosquitos.
The team observed an increase in mosquito attraction to malaria-infected mice, compared to healthy controls.
And the infected mice exhibited elevations in certain components of their natural scent, which suggests the malaria parasite changes the characteristics of its host’s body odor to make the host more attractive to mosquitos.
These findings appear in Proceedings of the National Academy of Sciences.
The researchers found that mice infected with Plasmodium chabaudii were more attractive to Anopheles stephensi mosquitos than uninfected control mice. And the attraction corresponded to an overall elevation in scent emissions from the infected mice.
However, malaria infection did not appear to trigger the expression of unique scent components. Instead, it seems the malaria pathogens alter the levels of compounds already present in the scent of uninfected mice.
“There appears to be an overall elevation of several compounds that are attractive to mosquitos,” said study author Consuelo De Moraes, PhD, of the Swiss Federal Institute of Technology in Zürich (ETH Zürich).
“Since mosquitos probably don’t benefit from feeding on infected people, it may make sense for the pathogen to exaggerate existing odor cues that the insects are already using for host location,” added study author Mark Mescher, PhD, also of ETH Zürich.
What the researchers found most surprising is the fact that the malaria infection leaves its mark on body odor long-term. Even when infected mice no longer had symptoms, their body odor showed they were carriers of the pathogen.
However, not all stages of disease smelled the same. The team found the scent profile of the acutely ill differed from the profile in mice exhibiting later stages of malaria infection.
Although the findings from this study cannot be directly translated to human malaria, they suggest similar effects might be involved in the attraction of mosquitos to infected people. Drs Mescher and De Moraes are currently investigating this possibility through additional research involving human subjects in Africa.
Credit: James Gathany
Scientists have found evidence to suggest that malaria parasites change the body odor of their host to attract hungry mosquitos.
The team observed an increase in mosquito attraction to malaria-infected mice, compared to healthy controls.
And the infected mice exhibited elevations in certain components of their natural scent, which suggests the malaria parasite changes the characteristics of its host’s body odor to make the host more attractive to mosquitos.
These findings appear in Proceedings of the National Academy of Sciences.
The researchers found that mice infected with Plasmodium chabaudii were more attractive to Anopheles stephensi mosquitos than uninfected control mice. And the attraction corresponded to an overall elevation in scent emissions from the infected mice.
However, malaria infection did not appear to trigger the expression of unique scent components. Instead, it seems the malaria pathogens alter the levels of compounds already present in the scent of uninfected mice.
“There appears to be an overall elevation of several compounds that are attractive to mosquitos,” said study author Consuelo De Moraes, PhD, of the Swiss Federal Institute of Technology in Zürich (ETH Zürich).
“Since mosquitos probably don’t benefit from feeding on infected people, it may make sense for the pathogen to exaggerate existing odor cues that the insects are already using for host location,” added study author Mark Mescher, PhD, also of ETH Zürich.
What the researchers found most surprising is the fact that the malaria infection leaves its mark on body odor long-term. Even when infected mice no longer had symptoms, their body odor showed they were carriers of the pathogen.
However, not all stages of disease smelled the same. The team found the scent profile of the acutely ill differed from the profile in mice exhibiting later stages of malaria infection.
Although the findings from this study cannot be directly translated to human malaria, they suggest similar effects might be involved in the attraction of mosquitos to infected people. Drs Mescher and De Moraes are currently investigating this possibility through additional research involving human subjects in Africa.
Credit: James Gathany
Scientists have found evidence to suggest that malaria parasites change the body odor of their host to attract hungry mosquitos.
The team observed an increase in mosquito attraction to malaria-infected mice, compared to healthy controls.
And the infected mice exhibited elevations in certain components of their natural scent, which suggests the malaria parasite changes the characteristics of its host’s body odor to make the host more attractive to mosquitos.
These findings appear in Proceedings of the National Academy of Sciences.
The researchers found that mice infected with Plasmodium chabaudii were more attractive to Anopheles stephensi mosquitos than uninfected control mice. And the attraction corresponded to an overall elevation in scent emissions from the infected mice.
However, malaria infection did not appear to trigger the expression of unique scent components. Instead, it seems the malaria pathogens alter the levels of compounds already present in the scent of uninfected mice.
“There appears to be an overall elevation of several compounds that are attractive to mosquitos,” said study author Consuelo De Moraes, PhD, of the Swiss Federal Institute of Technology in Zürich (ETH Zürich).
“Since mosquitos probably don’t benefit from feeding on infected people, it may make sense for the pathogen to exaggerate existing odor cues that the insects are already using for host location,” added study author Mark Mescher, PhD, also of ETH Zürich.
What the researchers found most surprising is the fact that the malaria infection leaves its mark on body odor long-term. Even when infected mice no longer had symptoms, their body odor showed they were carriers of the pathogen.
However, not all stages of disease smelled the same. The team found the scent profile of the acutely ill differed from the profile in mice exhibiting later stages of malaria infection.
Although the findings from this study cannot be directly translated to human malaria, they suggest similar effects might be involved in the attraction of mosquitos to infected people. Drs Mescher and De Moraes are currently investigating this possibility through additional research involving human subjects in Africa.
HSCT regimen could be ‘transformative’ for SCD
pre-HSCT (top) and post-HSCT
Credit: NIH Molecular and
Clinical Hematology Branch
In a small study, a nonmyeloablative hematopoietic stem cell transplant (HSCT) regimen reversed sickle cell disease (SCD) phenotype in a majority of adult patients, some of whom also had thalassemia.
Half of the patients were able to stop taking immunosuppressants and did not develop graft-vs-host disease (GVHD).
There were adverse events associated with the regimen, but the researchers believe it shows promise and could be “transformative” for patients with severe SCD.
The team described the regimen and its effects in JAMA.
Matthew M. Hsieh, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, and his colleagues first explored a nonmyeloablative HSCT approach in a pilot group of 10 adults with severe SCD.
The regimen had few toxic effects, but all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in patients with donor CD3 engraftment of greater than 50% and normalization of hemoglobin.
In JAMA, the team described the outcomes for 20 additional patients with severe SCD, with or without thalassemia, along with updated results from the first 10 patients.
All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013. Two patients had heterozygous hemoglobin S and C, 1 patient had HbSβ+-thalassemia, 1 patient had HbSβ0- thalassemia, and 1 had transfusion-dependent β-thalassemia intermedia. The remaining patients had homozygous hemoglobin S.
Patients received alemtuzumab (1mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and an infusion of unmanipulated, filgrastim-mobilized peripheral blood stem cells (5.5-31.7 × 106 cells/kg) from HLA-matched siblings.
There were 38 serious adverse events. The most common were pain-related (n=15), transplant-related infections (n=6), abdominal events (n=6), and toxic effects associated with sirolimus (n=5).
As of October 25, 2013, 29 patients were still alive, with a median follow-up of 3.4 years. Twenty-six patients (87%) had long-term stable donor engraftment without acute or chronic GVHD.
Hemoglobin levels improved after HSCT. At 1 year, 25 patients (83%) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and did not develop GVHD.
“Typically, stem cell recipients must take immunosuppressants all their lives,” Dr Hsieh noted. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
Hospitalization rates also decreased following HSCT. The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant.
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” Dr Hsieh pointed out. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg at 6 months after the transplant.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work, and long-term well-being,” said study author Griffin P. Rodgers, MD, director of the National Institute of Diabetes and Digestive and Kidney Diseases.
“This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem cell transplant or long-term use of immunosuppressants.”
pre-HSCT (top) and post-HSCT
Credit: NIH Molecular and
Clinical Hematology Branch
In a small study, a nonmyeloablative hematopoietic stem cell transplant (HSCT) regimen reversed sickle cell disease (SCD) phenotype in a majority of adult patients, some of whom also had thalassemia.
Half of the patients were able to stop taking immunosuppressants and did not develop graft-vs-host disease (GVHD).
There were adverse events associated with the regimen, but the researchers believe it shows promise and could be “transformative” for patients with severe SCD.
The team described the regimen and its effects in JAMA.
Matthew M. Hsieh, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, and his colleagues first explored a nonmyeloablative HSCT approach in a pilot group of 10 adults with severe SCD.
The regimen had few toxic effects, but all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in patients with donor CD3 engraftment of greater than 50% and normalization of hemoglobin.
In JAMA, the team described the outcomes for 20 additional patients with severe SCD, with or without thalassemia, along with updated results from the first 10 patients.
All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013. Two patients had heterozygous hemoglobin S and C, 1 patient had HbSβ+-thalassemia, 1 patient had HbSβ0- thalassemia, and 1 had transfusion-dependent β-thalassemia intermedia. The remaining patients had homozygous hemoglobin S.
Patients received alemtuzumab (1mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and an infusion of unmanipulated, filgrastim-mobilized peripheral blood stem cells (5.5-31.7 × 106 cells/kg) from HLA-matched siblings.
There were 38 serious adverse events. The most common were pain-related (n=15), transplant-related infections (n=6), abdominal events (n=6), and toxic effects associated with sirolimus (n=5).
As of October 25, 2013, 29 patients were still alive, with a median follow-up of 3.4 years. Twenty-six patients (87%) had long-term stable donor engraftment without acute or chronic GVHD.
Hemoglobin levels improved after HSCT. At 1 year, 25 patients (83%) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and did not develop GVHD.
“Typically, stem cell recipients must take immunosuppressants all their lives,” Dr Hsieh noted. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
Hospitalization rates also decreased following HSCT. The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant.
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” Dr Hsieh pointed out. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg at 6 months after the transplant.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work, and long-term well-being,” said study author Griffin P. Rodgers, MD, director of the National Institute of Diabetes and Digestive and Kidney Diseases.
“This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem cell transplant or long-term use of immunosuppressants.”
pre-HSCT (top) and post-HSCT
Credit: NIH Molecular and
Clinical Hematology Branch
In a small study, a nonmyeloablative hematopoietic stem cell transplant (HSCT) regimen reversed sickle cell disease (SCD) phenotype in a majority of adult patients, some of whom also had thalassemia.
Half of the patients were able to stop taking immunosuppressants and did not develop graft-vs-host disease (GVHD).
There were adverse events associated with the regimen, but the researchers believe it shows promise and could be “transformative” for patients with severe SCD.
The team described the regimen and its effects in JAMA.
Matthew M. Hsieh, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, and his colleagues first explored a nonmyeloablative HSCT approach in a pilot group of 10 adults with severe SCD.
The regimen had few toxic effects, but all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in patients with donor CD3 engraftment of greater than 50% and normalization of hemoglobin.
In JAMA, the team described the outcomes for 20 additional patients with severe SCD, with or without thalassemia, along with updated results from the first 10 patients.
All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013. Two patients had heterozygous hemoglobin S and C, 1 patient had HbSβ+-thalassemia, 1 patient had HbSβ0- thalassemia, and 1 had transfusion-dependent β-thalassemia intermedia. The remaining patients had homozygous hemoglobin S.
Patients received alemtuzumab (1mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and an infusion of unmanipulated, filgrastim-mobilized peripheral blood stem cells (5.5-31.7 × 106 cells/kg) from HLA-matched siblings.
There were 38 serious adverse events. The most common were pain-related (n=15), transplant-related infections (n=6), abdominal events (n=6), and toxic effects associated with sirolimus (n=5).
As of October 25, 2013, 29 patients were still alive, with a median follow-up of 3.4 years. Twenty-six patients (87%) had long-term stable donor engraftment without acute or chronic GVHD.
Hemoglobin levels improved after HSCT. At 1 year, 25 patients (83%) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and did not develop GVHD.
“Typically, stem cell recipients must take immunosuppressants all their lives,” Dr Hsieh noted. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
Hospitalization rates also decreased following HSCT. The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant.
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” Dr Hsieh pointed out. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg at 6 months after the transplant.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work, and long-term well-being,” said study author Griffin P. Rodgers, MD, director of the National Institute of Diabetes and Digestive and Kidney Diseases.
“This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem cell transplant or long-term use of immunosuppressants.”
Nature retracts STAP cell papers
Credit: Haruko Obokata
The journal Nature has retracted the papers it published several months ago on stimulus-triggered acquisition of pluripotency (STAP) cells.
In January, Nature published an article and a letter in which researchers claimed they could create STAP cells—ie, induce pluripotency in somatic cells by exposing them to a low-pH environment.
Not long after the papers were published, however, members of the scientific community began to question the validity of the research.
They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.
So the Japanese institute RIKEN, where most of the study’s investigators are employed, launched an investigation.
In April, RIKEN’s investigative committee concluded that lead study author Haruko Obokata, PhD, and some of her colleagues were guilty of misconduct and/or negligence.
Dr Obokata appealed the findings, saying the acts of misconduct were simply mistakes and that STAP cells do exist.
But the committee decided another investigation is not warranted, and RIKEN called for a retraction of the Nature papers.
Today, Nature published the retractions, which can be viewed here and here. An editorial on the subject is available here.
As for the future of STAP cells, RIKEN is currently attempting to recreate Dr Obokata’s experiments and determine if the cells do exist. The organization plans to release an interim report on this attempt in late July or early August.
Other researchers said they have tried and failed to replicate Dr Obokata’s experiments. One group detailed their failed attempt in F1000Research.
Credit: Haruko Obokata
The journal Nature has retracted the papers it published several months ago on stimulus-triggered acquisition of pluripotency (STAP) cells.
In January, Nature published an article and a letter in which researchers claimed they could create STAP cells—ie, induce pluripotency in somatic cells by exposing them to a low-pH environment.
Not long after the papers were published, however, members of the scientific community began to question the validity of the research.
They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.
So the Japanese institute RIKEN, where most of the study’s investigators are employed, launched an investigation.
In April, RIKEN’s investigative committee concluded that lead study author Haruko Obokata, PhD, and some of her colleagues were guilty of misconduct and/or negligence.
Dr Obokata appealed the findings, saying the acts of misconduct were simply mistakes and that STAP cells do exist.
But the committee decided another investigation is not warranted, and RIKEN called for a retraction of the Nature papers.
Today, Nature published the retractions, which can be viewed here and here. An editorial on the subject is available here.
As for the future of STAP cells, RIKEN is currently attempting to recreate Dr Obokata’s experiments and determine if the cells do exist. The organization plans to release an interim report on this attempt in late July or early August.
Other researchers said they have tried and failed to replicate Dr Obokata’s experiments. One group detailed their failed attempt in F1000Research.
Credit: Haruko Obokata
The journal Nature has retracted the papers it published several months ago on stimulus-triggered acquisition of pluripotency (STAP) cells.
In January, Nature published an article and a letter in which researchers claimed they could create STAP cells—ie, induce pluripotency in somatic cells by exposing them to a low-pH environment.
Not long after the papers were published, however, members of the scientific community began to question the validity of the research.
They voiced concerns about published images, possible plagiarism, and an inability to replicate the experiments described.
So the Japanese institute RIKEN, where most of the study’s investigators are employed, launched an investigation.
In April, RIKEN’s investigative committee concluded that lead study author Haruko Obokata, PhD, and some of her colleagues were guilty of misconduct and/or negligence.
Dr Obokata appealed the findings, saying the acts of misconduct were simply mistakes and that STAP cells do exist.
But the committee decided another investigation is not warranted, and RIKEN called for a retraction of the Nature papers.
Today, Nature published the retractions, which can be viewed here and here. An editorial on the subject is available here.
As for the future of STAP cells, RIKEN is currently attempting to recreate Dr Obokata’s experiments and determine if the cells do exist. The organization plans to release an interim report on this attempt in late July or early August.
Other researchers said they have tried and failed to replicate Dr Obokata’s experiments. One group detailed their failed attempt in F1000Research.
Company recalls lots of warfarin
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.