Related Issues

Burkitt lymphoma

Credit: Ed Uthman

Researchers say they’ve discovered how the protein STAT3 interferes with an antitumor mechanism in cells, thereby promoting the growth of lymphoma and other cancers.

The group made their discovery using the Epstein-Barr virus (EBV) as a tool to investigate cancer development.

“Our findings add to the short list of known mechanisms by which a key cellular antitumor barrier is breached by STAT3 prior to cancer development,” said Sumita Bhaduri-McIntosh, MD, PhD, of Stony Brook University School of Medicine in New York.

“Because STAT3 interferes with this innate antitumor mechanism in cells, the opposite occurs when blood cells are infected in the lab with the cancer-causing virus EBV, and the cells continue to divide—a necessary step in cancer development.”

Dr Bhaduri-McIntosh and her colleagues described their research in PNAS.

The team explained that STAT3 inhibits a cancer-suppressing cellular activity called the DNA damage response (DDR). Normally, this response pauses cell division, allowing for the repair of damaged DNA.

But this study showed that EBV not only causes DNA damage when it infects and replicates in cells; it also activates and increases STAT3 expression. This starts a chain reaction that leads to an “un-pause” in cell division, thereby promoting cell proliferation. This, in combination with other pro-proliferative effects of the virus, can lead to cancers.

The researchers found that DDR does detect replication stress-associated DNA damage resulting from EBV infection. But signaling downstream of ATR proteins is impaired by STAT3. And this leads to relaxation of the intra-S phase checkpoint of the cell cycle.

STAT3 interrupts signaling from ATR to the protein Chk1 by promoting the loss of Claspin, a protein that assists ATR to phosphorylate Chk1. The loss of Claspin, which facilitates cell proliferation, is mediated by caspase 7.

Previous research suggested that STAT3 and Chk1 are potential targets for cancer therapies. Dr Bhaduri-McIntosh’s team said their results provide new insight into anticancer drug development because they reveal a mechanistic link between these 2 proteins.

Dr Bhaduri-McIntosh emphasized that, because STAT3 is involved in most cancers, her group’s findings could potentially impact the prevention or treatment of several types of cancer—something her lab is investigating.

Burkitt lymphoma

Credit: Ed Uthman

Researchers say they’ve discovered how the protein STAT3 interferes with an antitumor mechanism in cells, thereby promoting the growth of lymphoma and other cancers.

The group made their discovery using the Epstein-Barr virus (EBV) as a tool to investigate cancer development.

“Our findings add to the short list of known mechanisms by which a key cellular antitumor barrier is breached by STAT3 prior to cancer development,” said Sumita Bhaduri-McIntosh, MD, PhD, of Stony Brook University School of Medicine in New York.

“Because STAT3 interferes with this innate antitumor mechanism in cells, the opposite occurs when blood cells are infected in the lab with the cancer-causing virus EBV, and the cells continue to divide—a necessary step in cancer development.”

Dr Bhaduri-McIntosh and her colleagues described their research in PNAS.

The team explained that STAT3 inhibits a cancer-suppressing cellular activity called the DNA damage response (DDR). Normally, this response pauses cell division, allowing for the repair of damaged DNA.

But this study showed that EBV not only causes DNA damage when it infects and replicates in cells; it also activates and increases STAT3 expression. This starts a chain reaction that leads to an “un-pause” in cell division, thereby promoting cell proliferation. This, in combination with other pro-proliferative effects of the virus, can lead to cancers.

The researchers found that DDR does detect replication stress-associated DNA damage resulting from EBV infection. But signaling downstream of ATR proteins is impaired by STAT3. And this leads to relaxation of the intra-S phase checkpoint of the cell cycle.

STAT3 interrupts signaling from ATR to the protein Chk1 by promoting the loss of Claspin, a protein that assists ATR to phosphorylate Chk1. The loss of Claspin, which facilitates cell proliferation, is mediated by caspase 7.

Previous research suggested that STAT3 and Chk1 are potential targets for cancer therapies. Dr Bhaduri-McIntosh’s team said their results provide new insight into anticancer drug development because they reveal a mechanistic link between these 2 proteins.

Dr Bhaduri-McIntosh emphasized that, because STAT3 is involved in most cancers, her group’s findings could potentially impact the prevention or treatment of several types of cancer—something her lab is investigating.

Burkitt lymphoma

Credit: Ed Uthman

Researchers say they’ve discovered how the protein STAT3 interferes with an antitumor mechanism in cells, thereby promoting the growth of lymphoma and other cancers.

The group made their discovery using the Epstein-Barr virus (EBV) as a tool to investigate cancer development.

“Our findings add to the short list of known mechanisms by which a key cellular antitumor barrier is breached by STAT3 prior to cancer development,” said Sumita Bhaduri-McIntosh, MD, PhD, of Stony Brook University School of Medicine in New York.

“Because STAT3 interferes with this innate antitumor mechanism in cells, the opposite occurs when blood cells are infected in the lab with the cancer-causing virus EBV, and the cells continue to divide—a necessary step in cancer development.”

Dr Bhaduri-McIntosh and her colleagues described their research in PNAS.

The team explained that STAT3 inhibits a cancer-suppressing cellular activity called the DNA damage response (DDR). Normally, this response pauses cell division, allowing for the repair of damaged DNA.

But this study showed that EBV not only causes DNA damage when it infects and replicates in cells; it also activates and increases STAT3 expression. This starts a chain reaction that leads to an “un-pause” in cell division, thereby promoting cell proliferation. This, in combination with other pro-proliferative effects of the virus, can lead to cancers.

The researchers found that DDR does detect replication stress-associated DNA damage resulting from EBV infection. But signaling downstream of ATR proteins is impaired by STAT3. And this leads to relaxation of the intra-S phase checkpoint of the cell cycle.

STAT3 interrupts signaling from ATR to the protein Chk1 by promoting the loss of Claspin, a protein that assists ATR to phosphorylate Chk1. The loss of Claspin, which facilitates cell proliferation, is mediated by caspase 7.

Previous research suggested that STAT3 and Chk1 are potential targets for cancer therapies. Dr Bhaduri-McIntosh’s team said their results provide new insight into anticancer drug development because they reveal a mechanistic link between these 2 proteins.

Dr Bhaduri-McIntosh emphasized that, because STAT3 is involved in most cancers, her group’s findings could potentially impact the prevention or treatment of several types of cancer—something her lab is investigating.

Foods commonly consumed as

part of a Mediterranean diet

In a large study, individuals who strictly followed a Mediterranean diet had lower levels of platelets and white blood cells (WBCs) than those who deviated from the diet.

And the lower cell counts were associated with lower levels of inflammation.

The research also suggested the diet as a whole, and not just certain components, was responsible for these markers of improved health.

Marialaura Bonaccio, PhD, of the IRCCS Istituto Neurologico Mediterraneo NEUROMED in Italy, and her colleagues reported these findings in Blood.

The team noted that the Mediterranean diet—which is characterized by a wide consumption of plant foods, cereals, legumes, fish, and olive oil, as well as moderate wine consumption—has long been hailed as a heart-healthy eating plan. And previous research suggested the diet can reduce inflammation.

But the connection between the diet and levels of platelets and WBCs, 2 specific inflammatory markers in the body, has remained unclear.

“We undertook this study to understand the correlation between consuming a Mediterranean diet and specific health markers, including platelet levels and white blood cell counts, which can more specifically explain the diet’s benefits in reducing the long-term risk of cerebral and heart disease or other chronic conditions,” Dr Bonaccio said.

To do this, she and her colleagues analyzed the eating habits of 14,586 healthy Italian men and women aged 35 and older. At baseline, all subjects were healthy.

The researchers measured total platelet and WBC counts and grouped participants according to their levels (low, normal, or high), based on age- and gender-specific cut-offs.

Participants with high platelet levels were younger and had a greater incidence of high cholesterol and increased levels of common inflammation marker C-reactive protein when compared to subjects in the normal or low-platelet categories.

Individuals in the high-WBC category were mainly younger, male, and smokers. They had a higher body-mass index and higher levels of C-reactive protein and blood glucose than subjects in the other groups. They also showed higher prevalence of high blood pressure and high cholesterol.

The researchers determined participants’ adherence to a Mediterranean using 2 dietary scoring systems, the Mediterranean diet score or the Italian Mediterranean Index, which helped to accurately determine intake levels and portion sizes.

Results of these analyses revealed that adherence to the Mediterranean diet was directly related to lower levels of platelets and WBCs (P<0.0001 and P=0.008, respectively), which was correlated with lower levels of inflammation.

When compared with participants who did not follow the eating plan as closely, subjects who strictly followed the diet were less likely to belong to the group with the highest platelet counts (odds ratio=0.50) and more likely to belong to the group with the lowest WBC counts (odds ratio=1.41).

“Because the study included healthy participants, the lower levels of platelets and white blood cells in those who were more strictly consuming a Mediterranean diet indicate that this eating plan could account for substantial changes within normal ranges of variability,” Dr Bonaccio said.

“This is an important finding that has implications for how these anti-inflammatory markers are tracked among the general population.”

The researchers also evaluated the role of specific components of the diet to help clarify the observed correlation, including food antioxidant content and fiber intake, both of which have previously been connected to cardiovascular benefits.

These components only partially accounted for the link between the diet and WBC count. And they did not fully explain the correlation to platelet levels.

“An important finding of this study is that it indicates that the Mediterranean diet as a whole, and not just a few specific ingredients, is likely responsible for the beneficial health outcomes among the healthy population and should be encouraged as part of healthy eating habits,” Dr Bonaccio said.

“Building on these important findings, we continue to study this population to determine if the dietary habits may have an influence on cardiovascular disease-related mortality.”

Foods commonly consumed as

part of a Mediterranean diet

In a large study, individuals who strictly followed a Mediterranean diet had lower levels of platelets and white blood cells (WBCs) than those who deviated from the diet.

And the lower cell counts were associated with lower levels of inflammation.

The research also suggested the diet as a whole, and not just certain components, was responsible for these markers of improved health.

Marialaura Bonaccio, PhD, of the IRCCS Istituto Neurologico Mediterraneo NEUROMED in Italy, and her colleagues reported these findings in Blood.

The team noted that the Mediterranean diet—which is characterized by a wide consumption of plant foods, cereals, legumes, fish, and olive oil, as well as moderate wine consumption—has long been hailed as a heart-healthy eating plan. And previous research suggested the diet can reduce inflammation.

But the connection between the diet and levels of platelets and WBCs, 2 specific inflammatory markers in the body, has remained unclear.

“We undertook this study to understand the correlation between consuming a Mediterranean diet and specific health markers, including platelet levels and white blood cell counts, which can more specifically explain the diet’s benefits in reducing the long-term risk of cerebral and heart disease or other chronic conditions,” Dr Bonaccio said.

To do this, she and her colleagues analyzed the eating habits of 14,586 healthy Italian men and women aged 35 and older. At baseline, all subjects were healthy.

The researchers measured total platelet and WBC counts and grouped participants according to their levels (low, normal, or high), based on age- and gender-specific cut-offs.

Participants with high platelet levels were younger and had a greater incidence of high cholesterol and increased levels of common inflammation marker C-reactive protein when compared to subjects in the normal or low-platelet categories.

Individuals in the high-WBC category were mainly younger, male, and smokers. They had a higher body-mass index and higher levels of C-reactive protein and blood glucose than subjects in the other groups. They also showed higher prevalence of high blood pressure and high cholesterol.

The researchers determined participants’ adherence to a Mediterranean using 2 dietary scoring systems, the Mediterranean diet score or the Italian Mediterranean Index, which helped to accurately determine intake levels and portion sizes.

Results of these analyses revealed that adherence to the Mediterranean diet was directly related to lower levels of platelets and WBCs (P<0.0001 and P=0.008, respectively), which was correlated with lower levels of inflammation.

When compared with participants who did not follow the eating plan as closely, subjects who strictly followed the diet were less likely to belong to the group with the highest platelet counts (odds ratio=0.50) and more likely to belong to the group with the lowest WBC counts (odds ratio=1.41).

“Because the study included healthy participants, the lower levels of platelets and white blood cells in those who were more strictly consuming a Mediterranean diet indicate that this eating plan could account for substantial changes within normal ranges of variability,” Dr Bonaccio said.

“This is an important finding that has implications for how these anti-inflammatory markers are tracked among the general population.”

The researchers also evaluated the role of specific components of the diet to help clarify the observed correlation, including food antioxidant content and fiber intake, both of which have previously been connected to cardiovascular benefits.

These components only partially accounted for the link between the diet and WBC count. And they did not fully explain the correlation to platelet levels.

“An important finding of this study is that it indicates that the Mediterranean diet as a whole, and not just a few specific ingredients, is likely responsible for the beneficial health outcomes among the healthy population and should be encouraged as part of healthy eating habits,” Dr Bonaccio said.

“Building on these important findings, we continue to study this population to determine if the dietary habits may have an influence on cardiovascular disease-related mortality.”

Foods commonly consumed as

part of a Mediterranean diet

In a large study, individuals who strictly followed a Mediterranean diet had lower levels of platelets and white blood cells (WBCs) than those who deviated from the diet.

And the lower cell counts were associated with lower levels of inflammation.

The research also suggested the diet as a whole, and not just certain components, was responsible for these markers of improved health.

Marialaura Bonaccio, PhD, of the IRCCS Istituto Neurologico Mediterraneo NEUROMED in Italy, and her colleagues reported these findings in Blood.

The team noted that the Mediterranean diet—which is characterized by a wide consumption of plant foods, cereals, legumes, fish, and olive oil, as well as moderate wine consumption—has long been hailed as a heart-healthy eating plan. And previous research suggested the diet can reduce inflammation.

But the connection between the diet and levels of platelets and WBCs, 2 specific inflammatory markers in the body, has remained unclear.

“We undertook this study to understand the correlation between consuming a Mediterranean diet and specific health markers, including platelet levels and white blood cell counts, which can more specifically explain the diet’s benefits in reducing the long-term risk of cerebral and heart disease or other chronic conditions,” Dr Bonaccio said.

To do this, she and her colleagues analyzed the eating habits of 14,586 healthy Italian men and women aged 35 and older. At baseline, all subjects were healthy.

The researchers measured total platelet and WBC counts and grouped participants according to their levels (low, normal, or high), based on age- and gender-specific cut-offs.

Participants with high platelet levels were younger and had a greater incidence of high cholesterol and increased levels of common inflammation marker C-reactive protein when compared to subjects in the normal or low-platelet categories.

Individuals in the high-WBC category were mainly younger, male, and smokers. They had a higher body-mass index and higher levels of C-reactive protein and blood glucose than subjects in the other groups. They also showed higher prevalence of high blood pressure and high cholesterol.

The researchers determined participants’ adherence to a Mediterranean using 2 dietary scoring systems, the Mediterranean diet score or the Italian Mediterranean Index, which helped to accurately determine intake levels and portion sizes.

Results of these analyses revealed that adherence to the Mediterranean diet was directly related to lower levels of platelets and WBCs (P<0.0001 and P=0.008, respectively), which was correlated with lower levels of inflammation.

When compared with participants who did not follow the eating plan as closely, subjects who strictly followed the diet were less likely to belong to the group with the highest platelet counts (odds ratio=0.50) and more likely to belong to the group with the lowest WBC counts (odds ratio=1.41).

“Because the study included healthy participants, the lower levels of platelets and white blood cells in those who were more strictly consuming a Mediterranean diet indicate that this eating plan could account for substantial changes within normal ranges of variability,” Dr Bonaccio said.

“This is an important finding that has implications for how these anti-inflammatory markers are tracked among the general population.”

The researchers also evaluated the role of specific components of the diet to help clarify the observed correlation, including food antioxidant content and fiber intake, both of which have previously been connected to cardiovascular benefits.

These components only partially accounted for the link between the diet and WBC count. And they did not fully explain the correlation to platelet levels.

“An important finding of this study is that it indicates that the Mediterranean diet as a whole, and not just a few specific ingredients, is likely responsible for the beneficial health outcomes among the healthy population and should be encouraged as part of healthy eating habits,” Dr Bonaccio said.

“Building on these important findings, we continue to study this population to determine if the dietary habits may have an influence on cardiovascular disease-related mortality.”

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Saline solution

In an attempt to alleviate the shortage of saline (0.9% sodium chloride injection) in the US, the Food and Drug Administration (FDA) is allowing saline products to be imported from Norway.

The company importing the products is Fresenius Kabi USA. The FDA inspected the company’s Norway manufacturing facility and found the site meets FDA standards.

So Fresenius Kabi has begun importing Sodium Chloride 0.9% Freeflex Injection Solution for Intravenous Infusion.

The European product contains the same active ingredient in the same concentration as the 0.9% sodium chloride injection products approved in the US.

For a complete list of all the Fresenius Kabi saline products, as well as a list of differences between the European and US prescribing information, see the “Dear Healthcare Professional” letter posted on the FDA website.

The FDA is asking that healthcare professionals contact Fresenius Kabi USA directly to obtain saline products. The company’s customer service number is 1-888-386-1300.

The FDA concedes that, while the shipments from Norway will help, they will not resolve the saline shortage. However, the agency says it is working closely with manufacturers to meet the needs for saline across the US.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Lone star tick

Credit: CDC

Health officials have reported 6 new cases of Heartland virus disease—5 in Missouri and 1 in Tennessee.

These cases, discovered in 2012 and 2013, add to the 2 cases discovered in 2009 and are described in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report.

The Heartland virus was first reported in 2 farmers in northwestern Missouri who were hospitalized in 2009 with what was thought to be ehrlichiosis, a tick-borne disease.

However, the patients failed to improve with treatment, and testing failed to confirm ehlrlichiosis.

Working with state and local partners, the CDC eventually identified the cause of the men’s illness: a previously unknown phlebovirus, now dubbed the Heartland virus.

Although we do not know for certain how patients are infected with the virus, research has suggested that ticks, namely lone star ticks, transmit it.

Ongoing investigations have uncovered 6 more cases of Heartland virus disease. All of the patients were white men older than 50 years of age. Five of them reported tick bites in the days or weeks before they fell ill.

Their symptoms started in May to September and included fever, fatigue, loss of appetite, headache, nausea, and muscle pain. The patients also had leukopenia and thrombocytopenia.

Four of the 6 patients were hospitalized. And 1 man, who suffered from other health conditions, died. It is not known if the Heartland virus was the cause of death or how much it contributed to his death.

The CDC has been working with the Missouri and Tennessee state health departments and other federal agencies to advance our understanding of Heartland virus disease by learning more about the patients who were infected, their illness, and their exposure to ticks.

The CDC aims to determine the symptoms and severity of the disease, where it is found, how people are being infected, and how to prevent infections.

CDC studies to date have shown that the Heartland virus is carried by lone star ticks, which are primarily found in the southeastern and eastern US.

Researchers hope additional studies can confirm whether ticks can spread the virus and reveal which other insects or animals may be involved in the transmission cycle. The CDC is also looking for the Heartland virus in other parts of the country to understand how widely it may be distributed.

“During the past 2 years, CDC has worked closely with state health departments, hospitals, and many experts from universities and other federal agencies to learn more about Heartland virus,” said Roger Nasci, PhD, chief of the CDC’s Arboviral Diseases Branch.

“By gathering information about the disease Heartland virus causes, and about how it’s spread to people, we hope to better understand the potential impact on the public’s health and how we can help protect people from this virus.”

The CDC developed the blood tests used to confirm the new cases of Heartland virus disease. CDC teams are working to further validate these tests and develop additional tests. The researchers hope to develop a diagnostic test that public health laboratories could use to test for the virus.

There is no specific treatment or vaccine for Heartland virus disease. However, supportive therapies such as intravenous fluids and fever reducers can relieve some symptoms of Heartland disease.

To reduce the risk of Heartland and other vector-borne diseases, the CDC recommends:

• Avoiding wooded and bushy areas with high grass and leaf litter
• Using insect repellent when outdoors
• Using products that contain permethrin on clothing
• Conducting a full-body tick check after spending time outdoors
• Bathing as soon as possible after coming indoors to wash off and more easily find any ticks
• Examining gear and pets, as ticks can “ride” into the home and attach to a person later.

For more information on the Heartland virus, visit the CDC website.

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Nurse treating cancer patient

Credit: Rhoda Baer

A new report shows the rate of invasive cancer among US men and women dropped slightly from 2009 to 2010, and the most common cancers were solid tumor malignancies.

However, non-Hodgkin lymphoma (NHL) consistently rated among the top 10 most common cancers, regardless of patient gender or race.

The report was prepared by the Centers for Disease Control and Prevention (CDC) and appears in the current Morbidity and Mortality Weekly Report.

Researchers analyzed new cases of invasive cancers diagnosed in 2010 and reported to the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and Results Program.

Data from all states (except Arkansas and Minnesota) and the District of Columbia were included in the analysis, which covered 97% of the US population.

The researchers found the rates of invasive cancer cases dropped from 459 per 100,000 people in 2009 to 446 per 100,000 in 2010.

Cancer rates were higher among men (503 per 100,000) than women (405 per 100,000). In all, there were 745,383 cases reported among men and 711,113 among women in 2010.

The highest rates were for cancers of the prostate (126 per 100,000), female breast (119 per 100,000), lung and bronchus (62 per 100,000), and colon and rectum (40 per 100,000). Together, these accounted for half of all cancer cases in the US.

However, hematologic malignancies were fairly common as well. NHL was the 6th most common cancer for men of all races/ethnicities except Hispanic. For this group, NHL was the 4th most common cancer.

NHL was the 7th most common cancer for black and white women and 6th for the remaining groups, which included American Indian/Alaskan native, Asian/Pacific Islander, and Hispanic women.

Leukemia and myeloma were also among the top 10 most common invasive cancers for certain patients.

Leukemia was the 9th most common cancer for Hispanic and white men and the 10th for American Indian/Alaskan Native women. Myeloma was the 8th most common cancer for black women.

Overall, cancer rates were highest among black patients (455 per 100,000), followed by whites (445 per 100,000), Hispanics (344 per 100,000), Asian/Pacific Islanders (289 per 100,000), and American Indians/Alaskan Natives (270 per 100,000).

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Red blood cells

Credit: NHLBI

Results of preclinical research could aid the development of new treatments for hemolysis, which may have implications for patients with sickle cell anemia and those who receive blood transfusions.

The researchers were investigating the possibility of using haptoglobin to prevent the chemical reactions triggered by hemoglobin after hemolysis.

Haptoglobin is known to bind acellular adult hemoglobin dimers and facilitate their clearance after hemolysis.

But haptoglobin exists in different forms. The 3 main phenotypes—Hp1-1, Hp2-1, and Hp2-2—have diverse structural configurations, and previous research suggested they have different biological activities.

With the current study, however, the researchers showed the different forms of haptoglobin actually exhibit similar activity.

Todd L. Mollan, PhD, of the Center for Biologics Evaluation and Research at the Food and Drug Administration in Bethesda, Maryland, and his colleagues presented these findings in Free Radical Biology and Medicine.

The researchers studied hemoglobin dimers in complex with unfractionated haptoglobin (a mixture of Hp1-1, Hp2-1, and Hp2-2); fractionated, dimeric haptoglobin (Hp1-1); and fractionated, polymeric haptoglobin (predominantly Hp2-2, with minor amounts of Hp2-1).

The team also complexed ferrous and ferric hemoglobins with unfractionated haptoglobin and its fractionated forms.

Experiments revealed no significant differences among the different complexes with regard to hemoglobin-haptoglobin binding kinetics, hydrogen-peroxide-driven oxidative transitions of the heme iron, radical formation, heme loss, or intrinsic redox potential.

The researchers said these results should be taken into account when designing phenotype-specific haptoglobin therapies.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Monoclonal antibodies

Credit: Linda Bartlett

The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending rituximab (MabThera) as a treatment option for adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The guidance applies to adults with severe microscopic polyangiitis or granulomatosis with polyangiitis.

The guidance recommends rituximab in combination with glucocorticoids for certain patients in this population.

According to NICE, the treatment is suitable only if:

• The patient is in danger of exceeding the maximum amount of cyclophosphamide
• The patient cannot or should not receive cyclophosphamide
• Loss of fertility (due to cyclophosphamide) is a concern
• The patient’s disease did not respond to a course of cyclophosphamide lasting 3 to 6 months
• The patient has had uroepithelial cancer.

About ANCA-associated vasculitis

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting the blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are types of ANCA-associated vasculitis that affect small blood vessels.

ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved, it can cause bleeding, rash, or deafness.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most patients with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

“The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients’ quality of life,” said Carole Longson, PhD, Health Technology Evaluation Centre Director at NICE.

“The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side effects that can further impair patients’ quality of life.”

Rituximab for ANCA-associated vasculitis

An independent advisory committee informed NICE that rituximab is a clinically effective and cost-effective option for some patients with severe microscopic polyangiitis or granulomatosis with polyangiitis.

“The committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s,” Dr Longson said. “In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients.”

“The committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance.”

Rituximab is priced at £174.63 per 10 mL vial and £873.15 per 50 mL vial (excluding tax). The manufacturer’s estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

Cultured blood cells showing

Staphylococcus infection

Credit: Bill Branson

About 1 in 25 US patients will contract at least 1 healthcare-associated infection (HAI) during the course of hospital care, according to data from the Centers for Disease Control and Prevention (CDC).

The agency has released 2 new reports on the topic.

The first, published in NEJM, is a survey of nearly 200 hospitals, which researchers used to estimate the national burden of HAIs in 2011.

The second is a 2012 annual report on the progress made toward US Health and Human Services HAI

prevention goals.

Together, the reports suggest that US hospitals have made progress in their effort to eliminate HAIs, but more work is needed to improve patient safety.

“Although there has been some progress, today and every day, more than 200 Americans with healthcare-associated infections will die during their hospital stay,” said CDC Director Tom Frieden, MD, MPH.

“The most advanced medical care won’t work if clinicians don’t prevent infections through basic things such as regular hand hygiene. Healthcare workers want the best for their patients. Following standard infection control practices every time will help ensure their patients’ safety.”

Estimating HAI incidence

The CDC Multistate Point-Prevalence Survey of Health Care-Associated Infections, published in NEJM, used 2011 data from 183 US hospitals to estimate the burden of a wide range of infections in hospital patients.

That year, about 721,800 infections occurred in 648,000 hospital patients. About 75,000 patients with HAIs died during their hospitalizations.

The most common infections were pneumonia (22%), surgical-site infections (22%), gastrointestinal infections (17%), urinary tract infections (13%), and bloodstream infections (10%).

The most common causes of HAIs were Clostridium difficile (12%), Staphylococcus aureus (including MRSA; 11%), Klebsiella (10%), Escherichia coli (9%), Enterococcus (9%), and Pseudomonas (7%).

Tracking national progress

The second report, CDC’s National and State Healthcare-associated Infection Progress Report, includes a subset of infection types that are often required to be reported to CDC.

The report revealed a 44% decrease in central line-associated bloodstream infections between 2008 and 2012, as well as a 20% decrease in infections related to 10 surgical procedures between 2008 and 2012.

There was a 4% decrease in hospital-onset MRSA between 2011 and 2012 and a 2% decrease in hospital-onset C difficile infections between 2011 and 2012.

On the other hand, there was a 3% increase in catheter-associated urinary tract infections between 2009 and 2012.

To access both reports and see the updated HAI data, visit the CDC website.

Cultured blood cells showing

Staphylococcus infection

Credit: Bill Branson

About 1 in 25 US patients will contract at least 1 healthcare-associated infection (HAI) during the course of hospital care, according to data from the Centers for Disease Control and Prevention (CDC).

The agency has released 2 new reports on the topic.

The first, published in NEJM, is a survey of nearly 200 hospitals, which researchers used to estimate the national burden of HAIs in 2011.

The second is a 2012 annual report on the progress made toward US Health and Human Services HAI

prevention goals.

Together, the reports suggest that US hospitals have made progress in their effort to eliminate HAIs, but more work is needed to improve patient safety.

“Although there has been some progress, today and every day, more than 200 Americans with healthcare-associated infections will die during their hospital stay,” said CDC Director Tom Frieden, MD, MPH.

“The most advanced medical care won’t work if clinicians don’t prevent infections through basic things such as regular hand hygiene. Healthcare workers want the best for their patients. Following standard infection control practices every time will help ensure their patients’ safety.”

Estimating HAI incidence

The CDC Multistate Point-Prevalence Survey of Health Care-Associated Infections, published in NEJM, used 2011 data from 183 US hospitals to estimate the burden of a wide range of infections in hospital patients.

That year, about 721,800 infections occurred in 648,000 hospital patients. About 75,000 patients with HAIs died during their hospitalizations.

The most common infections were pneumonia (22%), surgical-site infections (22%), gastrointestinal infections (17%), urinary tract infections (13%), and bloodstream infections (10%).

The most common causes of HAIs were Clostridium difficile (12%), Staphylococcus aureus (including MRSA; 11%), Klebsiella (10%), Escherichia coli (9%), Enterococcus (9%), and Pseudomonas (7%).

Tracking national progress

The second report, CDC’s National and State Healthcare-associated Infection Progress Report, includes a subset of infection types that are often required to be reported to CDC.

The report revealed a 44% decrease in central line-associated bloodstream infections between 2008 and 2012, as well as a 20% decrease in infections related to 10 surgical procedures between 2008 and 2012.

There was a 4% decrease in hospital-onset MRSA between 2011 and 2012 and a 2% decrease in hospital-onset C difficile infections between 2011 and 2012.

On the other hand, there was a 3% increase in catheter-associated urinary tract infections between 2009 and 2012.

To access both reports and see the updated HAI data, visit the CDC website.

Cultured blood cells showing

Staphylococcus infection

Credit: Bill Branson

About 1 in 25 US patients will contract at least 1 healthcare-associated infection (HAI) during the course of hospital care, according to data from the Centers for Disease Control and Prevention (CDC).

The agency has released 2 new reports on the topic.

The first, published in NEJM, is a survey of nearly 200 hospitals, which researchers used to estimate the national burden of HAIs in 2011.

The second is a 2012 annual report on the progress made toward US Health and Human Services HAI

prevention goals.

Together, the reports suggest that US hospitals have made progress in their effort to eliminate HAIs, but more work is needed to improve patient safety.

“Although there has been some progress, today and every day, more than 200 Americans with healthcare-associated infections will die during their hospital stay,” said CDC Director Tom Frieden, MD, MPH.

“The most advanced medical care won’t work if clinicians don’t prevent infections through basic things such as regular hand hygiene. Healthcare workers want the best for their patients. Following standard infection control practices every time will help ensure their patients’ safety.”

Estimating HAI incidence

The CDC Multistate Point-Prevalence Survey of Health Care-Associated Infections, published in NEJM, used 2011 data from 183 US hospitals to estimate the burden of a wide range of infections in hospital patients.

That year, about 721,800 infections occurred in 648,000 hospital patients. About 75,000 patients with HAIs died during their hospitalizations.

The most common infections were pneumonia (22%), surgical-site infections (22%), gastrointestinal infections (17%), urinary tract infections (13%), and bloodstream infections (10%).

The most common causes of HAIs were Clostridium difficile (12%), Staphylococcus aureus (including MRSA; 11%), Klebsiella (10%), Escherichia coli (9%), Enterococcus (9%), and Pseudomonas (7%).

Tracking national progress

The second report, CDC’s National and State Healthcare-associated Infection Progress Report, includes a subset of infection types that are often required to be reported to CDC.

The report revealed a 44% decrease in central line-associated bloodstream infections between 2008 and 2012, as well as a 20% decrease in infections related to 10 surgical procedures between 2008 and 2012.

There was a 4% decrease in hospital-onset MRSA between 2011 and 2012 and a 2% decrease in hospital-onset C difficile infections between 2011 and 2012.

On the other hand, there was a 3% increase in catheter-associated urinary tract infections between 2009 and 2012.

To access both reports and see the updated HAI data, visit the CDC website.

Mast cells

Research by an international consortium has revealed new information on hematopoiesis and shed new light on the etiology

of blood diseases.

The consortium, Functional Annotation of the Mammalian Genome (FANTOM), reported the results of this research in Blood.*

The investigators identified epigenetic regulators of hematopoiesis and uncovered the epigenetic and transcriptional changes that occur during granulopoiesis.

They “redefined” the mast cell transcriptome and mapped the enhancer and promoter landscapes of monocytes, conventional T cells, and regulatory T cells.

By pinpointing the locations of enhancers and promoters, the group was able to correlate them with activity in specific genes.

“Until this point, researchers could only recognize the unique signatures of enhancers and promoters,” said FANTOM investigator Alistair R.R. Forrest, PhD, of the RIKEN Centre for Life Science Technology in Yokohama, Japan.

“However, their exact location, as well as the association of specific enhancers to specific blood cells, remained unclear.”

Knowing the location of enhancers and promoters will improve experiments designed to determine how genes become activated, according to the investigators. And this could potentially lead to strategies for preventing or treating malignancies.

“The specific genetic alterations that are responsible for a normal cell turning into a cancer cell show up in the levels of messenger RNA in the cell, and these differences are often very subtle,” Dr Forrest said.

“Now that we have these incredibly detailed pictures of each of these cell types, we can now work backwards to compare cancer cells to the cells they came from originally to better understand what may have triggered the cells to malfunction, so we will be better equipped to develop new and more effective therapies.”

*The studies include:

Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation

High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis

Redefinition of the human mast cell transcriptome by deep-CAGE sequencing

Transcription and enhancer profiling in human monocyte subsets

The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations.

Mast cells

Research by an international consortium has revealed new information on hematopoiesis and shed new light on the etiology

of blood diseases.

The consortium, Functional Annotation of the Mammalian Genome (FANTOM), reported the results of this research in Blood.*

The investigators identified epigenetic regulators of hematopoiesis and uncovered the epigenetic and transcriptional changes that occur during granulopoiesis.

They “redefined” the mast cell transcriptome and mapped the enhancer and promoter landscapes of monocytes, conventional T cells, and regulatory T cells.

By pinpointing the locations of enhancers and promoters, the group was able to correlate them with activity in specific genes.

“Until this point, researchers could only recognize the unique signatures of enhancers and promoters,” said FANTOM investigator Alistair R.R. Forrest, PhD, of the RIKEN Centre for Life Science Technology in Yokohama, Japan.

“However, their exact location, as well as the association of specific enhancers to specific blood cells, remained unclear.”

Knowing the location of enhancers and promoters will improve experiments designed to determine how genes become activated, according to the investigators. And this could potentially lead to strategies for preventing or treating malignancies.

“The specific genetic alterations that are responsible for a normal cell turning into a cancer cell show up in the levels of messenger RNA in the cell, and these differences are often very subtle,” Dr Forrest said.

“Now that we have these incredibly detailed pictures of each of these cell types, we can now work backwards to compare cancer cells to the cells they came from originally to better understand what may have triggered the cells to malfunction, so we will be better equipped to develop new and more effective therapies.”

*The studies include:

Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation

High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis

Redefinition of the human mast cell transcriptome by deep-CAGE sequencing

Transcription and enhancer profiling in human monocyte subsets

The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations.

Mast cells

Research by an international consortium has revealed new information on hematopoiesis and shed new light on the etiology

of blood diseases.

The consortium, Functional Annotation of the Mammalian Genome (FANTOM), reported the results of this research in Blood.*

The investigators identified epigenetic regulators of hematopoiesis and uncovered the epigenetic and transcriptional changes that occur during granulopoiesis.

They “redefined” the mast cell transcriptome and mapped the enhancer and promoter landscapes of monocytes, conventional T cells, and regulatory T cells.

By pinpointing the locations of enhancers and promoters, the group was able to correlate them with activity in specific genes.

“Until this point, researchers could only recognize the unique signatures of enhancers and promoters,” said FANTOM investigator Alistair R.R. Forrest, PhD, of the RIKEN Centre for Life Science Technology in Yokohama, Japan.

“However, their exact location, as well as the association of specific enhancers to specific blood cells, remained unclear.”

Knowing the location of enhancers and promoters will improve experiments designed to determine how genes become activated, according to the investigators. And this could potentially lead to strategies for preventing or treating malignancies.

“The specific genetic alterations that are responsible for a normal cell turning into a cancer cell show up in the levels of messenger RNA in the cell, and these differences are often very subtle,” Dr Forrest said.

“Now that we have these incredibly detailed pictures of each of these cell types, we can now work backwards to compare cancer cells to the cells they came from originally to better understand what may have triggered the cells to malfunction, so we will be better equipped to develop new and more effective therapies.”

*The studies include:

Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation

High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis

Redefinition of the human mast cell transcriptome by deep-CAGE sequencing

Transcription and enhancer profiling in human monocyte subsets

The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations.

NK cell destroying a cancer cell

Credit: St Jude Children’s

Research Hospital

Researchers say they’ve gained new insight into the production of natural killer (NK) cells.

And their findings may help them generate greater numbers of the cells in culture, which could have implications for the treatment of leukemia and other malignancies.

A previous study conducted by the same team revealed that the gene E4bp4 must be switched on to allow the immune system to produce NK cells.

Their new work suggests that E4bp4 expression is required for progenitor cells to commit to the NK lineage. And the gene promotes NK-cell development by regulating expression of the transcription factors Eomes and Id2.

The researchers described these discoveries in the Journal of Experimental Medicine.

“We are excited to find that E4bp4 has such a crucial role in determining the decisive point where blood progenitor cells become NK cells,” said study author Hugh Brady, of Imperial College London in the UK.

“We are now starting to apply this to human blood stem cells to work out how switching on E4bp4 can allow us to make lots of robust human NK cells in culture. We are hoping to make human NK cells that will have improved survival and be very toxic to cancer cells when transfused into patients. Hopefully, this will allow a big reduction in the number of NK cells needed to treat an individual patient.”

To gain insight into NK-cell production, Dr Brady and his colleagues evaluated 2 types of mice with NK-cell deficiencies. The Il15ra knockout mouse model cannot mediate IL-15 signaling, which is critical for NK-cell production. And the T-bet (Tbx21) knockout model lacks a transcription factor that’s crucial for NK-cell development.

Analysis of the Il15ra model revealed that the absence of E4bp4 perturbs NK-cell development earlier than the absence of IL-15 signaling. This suggests E4bp4 acts before IL-15, which was previously considered the definitive factor required for NK-cell production.

The researchers also found that E4bp4 is required for the production of NK progenitors, but T-bet is not. And this suggests E4bp4 acts before T-bet in NK-cell development.

To investigate these findings further, the team took cells at various stages of NK-cell differentiation from wild-type bone marrow and measured their expression of transcription factor mRNAs.

They detected E4bp4 transcript in both lymphoid-primed multipotent progenitors (LMPPs) and common lymphoid progenitors (CLPs), and E4bp4 expression increased at later stages of NK-cell development.

Based on these results, the researchers speculated that E4bp4 might be a lineage commitment factor controlling the development of NK progenitors from CLPs. To test that theory, they restored E4bp4 expression in purified E4bp4-/- CLPs to see if this could re-establish NK-cell development.

The team sorted CLPs from E4bp4-/- bone marrow, cultured them in lymphocyte-inducing conditions, transduced them with E4bp4 or empty vector, and moved on to NK-cell-inducing conditions. But neither cell type produced NK cells.

So the researchers decided to initiate the culture at an earlier developmental stage, using LMPPs. They cultured LMPPs, which exhibited a CLP phenotype at the time of transduction. And CLPs transduced with E4bp4 gave rise to NK cells, but CLPs transduced with empty vector did not.

As these results suggest that E4bp4 acts at the earliest possible point in NK-cell development, the team wanted to characterize E4bp4’s relationship with transcription factors that are likely to act downstream.

They tested several transcription factors known to play a part in NK-cell production and function. But only Eomes and Id2 proved essential for E4bp4 to direct the production of fully functional, mature NK cells.

NK cell destroying a cancer cell

Credit: St Jude Children’s

Research Hospital

Researchers say they’ve gained new insight into the production of natural killer (NK) cells.

And their findings may help them generate greater numbers of the cells in culture, which could have implications for the treatment of leukemia and other malignancies.

A previous study conducted by the same team revealed that the gene E4bp4 must be switched on to allow the immune system to produce NK cells.

Their new work suggests that E4bp4 expression is required for progenitor cells to commit to the NK lineage. And the gene promotes NK-cell development by regulating expression of the transcription factors Eomes and Id2.

The researchers described these discoveries in the Journal of Experimental Medicine.

“We are excited to find that E4bp4 has such a crucial role in determining the decisive point where blood progenitor cells become NK cells,” said study author Hugh Brady, of Imperial College London in the UK.

“We are now starting to apply this to human blood stem cells to work out how switching on E4bp4 can allow us to make lots of robust human NK cells in culture. We are hoping to make human NK cells that will have improved survival and be very toxic to cancer cells when transfused into patients. Hopefully, this will allow a big reduction in the number of NK cells needed to treat an individual patient.”

To gain insight into NK-cell production, Dr Brady and his colleagues evaluated 2 types of mice with NK-cell deficiencies. The Il15ra knockout mouse model cannot mediate IL-15 signaling, which is critical for NK-cell production. And the T-bet (Tbx21) knockout model lacks a transcription factor that’s crucial for NK-cell development.

Analysis of the Il15ra model revealed that the absence of E4bp4 perturbs NK-cell development earlier than the absence of IL-15 signaling. This suggests E4bp4 acts before IL-15, which was previously considered the definitive factor required for NK-cell production.

The researchers also found that E4bp4 is required for the production of NK progenitors, but T-bet is not. And this suggests E4bp4 acts before T-bet in NK-cell development.

To investigate these findings further, the team took cells at various stages of NK-cell differentiation from wild-type bone marrow and measured their expression of transcription factor mRNAs.

They detected E4bp4 transcript in both lymphoid-primed multipotent progenitors (LMPPs) and common lymphoid progenitors (CLPs), and E4bp4 expression increased at later stages of NK-cell development.

Based on these results, the researchers speculated that E4bp4 might be a lineage commitment factor controlling the development of NK progenitors from CLPs. To test that theory, they restored E4bp4 expression in purified E4bp4-/- CLPs to see if this could re-establish NK-cell development.

The team sorted CLPs from E4bp4-/- bone marrow, cultured them in lymphocyte-inducing conditions, transduced them with E4bp4 or empty vector, and moved on to NK-cell-inducing conditions. But neither cell type produced NK cells.

So the researchers decided to initiate the culture at an earlier developmental stage, using LMPPs. They cultured LMPPs, which exhibited a CLP phenotype at the time of transduction. And CLPs transduced with E4bp4 gave rise to NK cells, but CLPs transduced with empty vector did not.

As these results suggest that E4bp4 acts at the earliest possible point in NK-cell development, the team wanted to characterize E4bp4’s relationship with transcription factors that are likely to act downstream.

They tested several transcription factors known to play a part in NK-cell production and function. But only Eomes and Id2 proved essential for E4bp4 to direct the production of fully functional, mature NK cells.

NK cell destroying a cancer cell

Credit: St Jude Children’s

Research Hospital

Researchers say they’ve gained new insight into the production of natural killer (NK) cells.

And their findings may help them generate greater numbers of the cells in culture, which could have implications for the treatment of leukemia and other malignancies.

A previous study conducted by the same team revealed that the gene E4bp4 must be switched on to allow the immune system to produce NK cells.

Their new work suggests that E4bp4 expression is required for progenitor cells to commit to the NK lineage. And the gene promotes NK-cell development by regulating expression of the transcription factors Eomes and Id2.

The researchers described these discoveries in the Journal of Experimental Medicine.

“We are excited to find that E4bp4 has such a crucial role in determining the decisive point where blood progenitor cells become NK cells,” said study author Hugh Brady, of Imperial College London in the UK.

“We are now starting to apply this to human blood stem cells to work out how switching on E4bp4 can allow us to make lots of robust human NK cells in culture. We are hoping to make human NK cells that will have improved survival and be very toxic to cancer cells when transfused into patients. Hopefully, this will allow a big reduction in the number of NK cells needed to treat an individual patient.”

To gain insight into NK-cell production, Dr Brady and his colleagues evaluated 2 types of mice with NK-cell deficiencies. The Il15ra knockout mouse model cannot mediate IL-15 signaling, which is critical for NK-cell production. And the T-bet (Tbx21) knockout model lacks a transcription factor that’s crucial for NK-cell development.

Analysis of the Il15ra model revealed that the absence of E4bp4 perturbs NK-cell development earlier than the absence of IL-15 signaling. This suggests E4bp4 acts before IL-15, which was previously considered the definitive factor required for NK-cell production.

The researchers also found that E4bp4 is required for the production of NK progenitors, but T-bet is not. And this suggests E4bp4 acts before T-bet in NK-cell development.

To investigate these findings further, the team took cells at various stages of NK-cell differentiation from wild-type bone marrow and measured their expression of transcription factor mRNAs.

They detected E4bp4 transcript in both lymphoid-primed multipotent progenitors (LMPPs) and common lymphoid progenitors (CLPs), and E4bp4 expression increased at later stages of NK-cell development.

Based on these results, the researchers speculated that E4bp4 might be a lineage commitment factor controlling the development of NK progenitors from CLPs. To test that theory, they restored E4bp4 expression in purified E4bp4-/- CLPs to see if this could re-establish NK-cell development.

The team sorted CLPs from E4bp4-/- bone marrow, cultured them in lymphocyte-inducing conditions, transduced them with E4bp4 or empty vector, and moved on to NK-cell-inducing conditions. But neither cell type produced NK cells.

So the researchers decided to initiate the culture at an earlier developmental stage, using LMPPs. They cultured LMPPs, which exhibited a CLP phenotype at the time of transduction. And CLPs transduced with E4bp4 gave rise to NK cells, but CLPs transduced with empty vector did not.

As these results suggest that E4bp4 acts at the earliest possible point in NK-cell development, the team wanted to characterize E4bp4’s relationship with transcription factors that are likely to act downstream.

They tested several transcription factors known to play a part in NK-cell production and function. But only Eomes and Id2 proved essential for E4bp4 to direct the production of fully functional, mature NK cells.