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Patients may need extended VTE prophylaxis, doc says
Photo by Andre E.X. Brown
SEATTLE—Patients who undergo surgery for lung cancer may have a higher risk of developing venous thromboembolism (VTE) than we thought, according to a
new study.
About 12% of the patients studied developed deep vein thrombosis (DVT), pulmonary embolism (PE), or both, although they had received VTE prophylaxis until hospital discharge.
Only about 21% of these patients showed symptoms of VTE, and the clots conferred a higher risk of mortality at 30 days.
“This study shows that a significant proportion of lung cancer surgery patients are at risk of VTE and indicates a need for future research into minimizing the occurrence of DVT and PE,” said investigator Yaron Shargall, MD, of McMaster University in Hamilton, Ontario, Canada.
“It is possible that extended use of blood thinners beyond hospital discharge may reduce the number of patients who experience these life-threatening events and may help to reduce the rates of death after lung surgery.”
Dr Shargall presented this viewpoint at the 95th Annual Meeting of the American Association for Thoracic Surgery.
For their study, he and his colleagues evaluated 157 patients who underwent thoracic surgery for primary lung cancer (89.9%) or metastatic cancer (6.3%).
All patients received unfractionated heparin or low-molecular-weight heparin and graduated compression stockings as VTE prophylaxis from the time of surgery until leaving the hospital.
Two weeks later, these patients were evaluated for signs and symptoms of VTE. The investigators evaluated clinical outcomes at 30 ± 5 days post-operatively using CT pulmonary angiography and bilateral Doppler venous ultrasonography.
Patients who had developed symptoms suggestive of VTE within the 30 days after surgery underwent urgent CT-PE examination and had a repeat scan 30 days after surgery if the first scan was negative. Patients with VTE were monitored and treated.
In all, there were 19 VTEs, a 12.1% incidence rate. These included 14 PEs (8.9%), 3 DVTs (1.9%), and 1 combined PE/DVT. One patient developed a massive left atrial thrombus originating from a surgical stump and died.
For all 157 patients, the 30-day mortality rate was 0.64%. For those with VTE, it was 5.2%.
“This demonstrates the clinical importance and relative fatality of VTE following lung cancer surgery,” Dr Shargall said.
All of the patients who were diagnosed with a VTE had undergone anatomic resections (lobectomy or segmentectomy), and most had primary lung cancer. The clots tended to form on the same side as the lung surgery. The majority of patients developed lung clots without forming DVTs beforehand.
The investigators examined factors that might distinguish patients who developed VTEs from those who did not and could not find differences in patient age, lung function, hospital length of stay, comorbidities, lung cancer stage, smoking status, or Caprini Score.
Among patients diagnosed with a VTE, only 4 (21.1%) showed symptoms. All the events were diagnosed after the patient left the hospital and only because these patients were screened for VTEs as part of the study. 
Photo by Andre E.X. Brown
SEATTLE—Patients who undergo surgery for lung cancer may have a higher risk of developing venous thromboembolism (VTE) than we thought, according to a
new study.
About 12% of the patients studied developed deep vein thrombosis (DVT), pulmonary embolism (PE), or both, although they had received VTE prophylaxis until hospital discharge.
Only about 21% of these patients showed symptoms of VTE, and the clots conferred a higher risk of mortality at 30 days.
“This study shows that a significant proportion of lung cancer surgery patients are at risk of VTE and indicates a need for future research into minimizing the occurrence of DVT and PE,” said investigator Yaron Shargall, MD, of McMaster University in Hamilton, Ontario, Canada.
“It is possible that extended use of blood thinners beyond hospital discharge may reduce the number of patients who experience these life-threatening events and may help to reduce the rates of death after lung surgery.”
Dr Shargall presented this viewpoint at the 95th Annual Meeting of the American Association for Thoracic Surgery.
For their study, he and his colleagues evaluated 157 patients who underwent thoracic surgery for primary lung cancer (89.9%) or metastatic cancer (6.3%).
All patients received unfractionated heparin or low-molecular-weight heparin and graduated compression stockings as VTE prophylaxis from the time of surgery until leaving the hospital.
Two weeks later, these patients were evaluated for signs and symptoms of VTE. The investigators evaluated clinical outcomes at 30 ± 5 days post-operatively using CT pulmonary angiography and bilateral Doppler venous ultrasonography.
Patients who had developed symptoms suggestive of VTE within the 30 days after surgery underwent urgent CT-PE examination and had a repeat scan 30 days after surgery if the first scan was negative. Patients with VTE were monitored and treated.
In all, there were 19 VTEs, a 12.1% incidence rate. These included 14 PEs (8.9%), 3 DVTs (1.9%), and 1 combined PE/DVT. One patient developed a massive left atrial thrombus originating from a surgical stump and died.
For all 157 patients, the 30-day mortality rate was 0.64%. For those with VTE, it was 5.2%.
“This demonstrates the clinical importance and relative fatality of VTE following lung cancer surgery,” Dr Shargall said.
All of the patients who were diagnosed with a VTE had undergone anatomic resections (lobectomy or segmentectomy), and most had primary lung cancer. The clots tended to form on the same side as the lung surgery. The majority of patients developed lung clots without forming DVTs beforehand.
The investigators examined factors that might distinguish patients who developed VTEs from those who did not and could not find differences in patient age, lung function, hospital length of stay, comorbidities, lung cancer stage, smoking status, or Caprini Score.
Among patients diagnosed with a VTE, only 4 (21.1%) showed symptoms. All the events were diagnosed after the patient left the hospital and only because these patients were screened for VTEs as part of the study.
Photo by Andre E.X. Brown
SEATTLE—Patients who undergo surgery for lung cancer may have a higher risk of developing venous thromboembolism (VTE) than we thought, according to a
new study.
About 12% of the patients studied developed deep vein thrombosis (DVT), pulmonary embolism (PE), or both, although they had received VTE prophylaxis until hospital discharge.
Only about 21% of these patients showed symptoms of VTE, and the clots conferred a higher risk of mortality at 30 days.
“This study shows that a significant proportion of lung cancer surgery patients are at risk of VTE and indicates a need for future research into minimizing the occurrence of DVT and PE,” said investigator Yaron Shargall, MD, of McMaster University in Hamilton, Ontario, Canada.
“It is possible that extended use of blood thinners beyond hospital discharge may reduce the number of patients who experience these life-threatening events and may help to reduce the rates of death after lung surgery.”
Dr Shargall presented this viewpoint at the 95th Annual Meeting of the American Association for Thoracic Surgery.
For their study, he and his colleagues evaluated 157 patients who underwent thoracic surgery for primary lung cancer (89.9%) or metastatic cancer (6.3%).
All patients received unfractionated heparin or low-molecular-weight heparin and graduated compression stockings as VTE prophylaxis from the time of surgery until leaving the hospital.
Two weeks later, these patients were evaluated for signs and symptoms of VTE. The investigators evaluated clinical outcomes at 30 ± 5 days post-operatively using CT pulmonary angiography and bilateral Doppler venous ultrasonography.
Patients who had developed symptoms suggestive of VTE within the 30 days after surgery underwent urgent CT-PE examination and had a repeat scan 30 days after surgery if the first scan was negative. Patients with VTE were monitored and treated.
In all, there were 19 VTEs, a 12.1% incidence rate. These included 14 PEs (8.9%), 3 DVTs (1.9%), and 1 combined PE/DVT. One patient developed a massive left atrial thrombus originating from a surgical stump and died.
For all 157 patients, the 30-day mortality rate was 0.64%. For those with VTE, it was 5.2%.
“This demonstrates the clinical importance and relative fatality of VTE following lung cancer surgery,” Dr Shargall said.
All of the patients who were diagnosed with a VTE had undergone anatomic resections (lobectomy or segmentectomy), and most had primary lung cancer. The clots tended to form on the same side as the lung surgery. The majority of patients developed lung clots without forming DVTs beforehand.
The investigators examined factors that might distinguish patients who developed VTEs from those who did not and could not find differences in patient age, lung function, hospital length of stay, comorbidities, lung cancer stage, smoking status, or Caprini Score.
Among patients diagnosed with a VTE, only 4 (21.1%) showed symptoms. All the events were diagnosed after the patient left the hospital and only because these patients were screened for VTEs as part of the study.
Simpler, more cost-effective way to grow stem cells
Photo courtesy of University
of Texas at El Paso
Researchers say they have developed a protocol to prepare human induced pluripotent stem (hiPS) cells using chemically fixed feeder cells.
This method saves time and money by avoiding the need for colony formation of live feeder cells, which is required by current conventional methods.
The new protocol challenges the theory that live feeder cells are required to provide nutrients to growing stem cells.
“We’ve proved an important phenomenon,” said Binata Joddar, PhD, of the University of Texas at El Paso. “And it suggests that these feeder cells, which are difficult to grow, may not be important at all for stem cell growth.”
Dr Joddar and her colleagues described the phenomenon in Journal of Materials Chemistry B.
Using 2.5% glutaraldehyde (GA) or formaldehyde (FA) for 10 minutes, the researchers prepared a niche matrix from autologus human dermal fibroblast (HDF) feeder cells.
They then introduced hiPS cells to the niche matrix, which adhered to and were maintained as colonies on the fixed feeder cells.
The colony doubling times of the cells grown this way were similar to those of hiPS cells grown on mitomycin-C-treated HDF or SNL feeders. (SNL cells are derived from mouse fibroblast STO cells transformed with a neomycin resistance gene.)
But the colony doubling time for the hiPS cells was shorter with the fixed feeder than for cells cultured on laminin-5.
The researchers also discovered that the average number of colonies per passage was signficiantly higher for hiPS cells cultured on fixed feeder cells compared to those cultured without feeders.
They noted hiPS cells cultured on gelatin did not grow beyond the first passage.
The team concluded that the two types of chemically fixed HDF feeder cells (HDF-glutaraldehyde and HDF-formaldehyde) can be used as substitutes for mitomycin-C-treated HDF feeders to culture hiPS cells.
This new method would not extend the doubling time, would save preparation time, and would avoid labor-intensive protocols to prepare.
In addition, after chemical fixation, the feeder cells are non-viable and cannot release active growth factors or chemokines into the cell culture. Therefore, fixed feeder cells can be refrigerated for long-term storage prior to use.
“Because feeder cells don’t need to stay alive in the process, we can store them at room temperature and spend less time cultivating them,” Dr Joddar said.
“This makes me think that we [could] use a nanomanufacturing approach to grow stem cells. We could mimic feeder cells’ nanotopology with 3-D printing techniques and skip using feeder cells altogether in the future.”
Photo courtesy of University
of Texas at El Paso
Researchers say they have developed a protocol to prepare human induced pluripotent stem (hiPS) cells using chemically fixed feeder cells.
This method saves time and money by avoiding the need for colony formation of live feeder cells, which is required by current conventional methods.
The new protocol challenges the theory that live feeder cells are required to provide nutrients to growing stem cells.
“We’ve proved an important phenomenon,” said Binata Joddar, PhD, of the University of Texas at El Paso. “And it suggests that these feeder cells, which are difficult to grow, may not be important at all for stem cell growth.”
Dr Joddar and her colleagues described the phenomenon in Journal of Materials Chemistry B.
Using 2.5% glutaraldehyde (GA) or formaldehyde (FA) for 10 minutes, the researchers prepared a niche matrix from autologus human dermal fibroblast (HDF) feeder cells.
They then introduced hiPS cells to the niche matrix, which adhered to and were maintained as colonies on the fixed feeder cells.
The colony doubling times of the cells grown this way were similar to those of hiPS cells grown on mitomycin-C-treated HDF or SNL feeders. (SNL cells are derived from mouse fibroblast STO cells transformed with a neomycin resistance gene.)
But the colony doubling time for the hiPS cells was shorter with the fixed feeder than for cells cultured on laminin-5.
The researchers also discovered that the average number of colonies per passage was signficiantly higher for hiPS cells cultured on fixed feeder cells compared to those cultured without feeders.
They noted hiPS cells cultured on gelatin did not grow beyond the first passage.
The team concluded that the two types of chemically fixed HDF feeder cells (HDF-glutaraldehyde and HDF-formaldehyde) can be used as substitutes for mitomycin-C-treated HDF feeders to culture hiPS cells.
This new method would not extend the doubling time, would save preparation time, and would avoid labor-intensive protocols to prepare.
In addition, after chemical fixation, the feeder cells are non-viable and cannot release active growth factors or chemokines into the cell culture. Therefore, fixed feeder cells can be refrigerated for long-term storage prior to use.
“Because feeder cells don’t need to stay alive in the process, we can store them at room temperature and spend less time cultivating them,” Dr Joddar said.
“This makes me think that we [could] use a nanomanufacturing approach to grow stem cells. We could mimic feeder cells’ nanotopology with 3-D printing techniques and skip using feeder cells altogether in the future.”
Photo courtesy of University
of Texas at El Paso
Researchers say they have developed a protocol to prepare human induced pluripotent stem (hiPS) cells using chemically fixed feeder cells.
This method saves time and money by avoiding the need for colony formation of live feeder cells, which is required by current conventional methods.
The new protocol challenges the theory that live feeder cells are required to provide nutrients to growing stem cells.
“We’ve proved an important phenomenon,” said Binata Joddar, PhD, of the University of Texas at El Paso. “And it suggests that these feeder cells, which are difficult to grow, may not be important at all for stem cell growth.”
Dr Joddar and her colleagues described the phenomenon in Journal of Materials Chemistry B.
Using 2.5% glutaraldehyde (GA) or formaldehyde (FA) for 10 minutes, the researchers prepared a niche matrix from autologus human dermal fibroblast (HDF) feeder cells.
They then introduced hiPS cells to the niche matrix, which adhered to and were maintained as colonies on the fixed feeder cells.
The colony doubling times of the cells grown this way were similar to those of hiPS cells grown on mitomycin-C-treated HDF or SNL feeders. (SNL cells are derived from mouse fibroblast STO cells transformed with a neomycin resistance gene.)
But the colony doubling time for the hiPS cells was shorter with the fixed feeder than for cells cultured on laminin-5.
The researchers also discovered that the average number of colonies per passage was signficiantly higher for hiPS cells cultured on fixed feeder cells compared to those cultured without feeders.
They noted hiPS cells cultured on gelatin did not grow beyond the first passage.
The team concluded that the two types of chemically fixed HDF feeder cells (HDF-glutaraldehyde and HDF-formaldehyde) can be used as substitutes for mitomycin-C-treated HDF feeders to culture hiPS cells.
This new method would not extend the doubling time, would save preparation time, and would avoid labor-intensive protocols to prepare.
In addition, after chemical fixation, the feeder cells are non-viable and cannot release active growth factors or chemokines into the cell culture. Therefore, fixed feeder cells can be refrigerated for long-term storage prior to use.
“Because feeder cells don’t need to stay alive in the process, we can store them at room temperature and spend less time cultivating them,” Dr Joddar said.
“This makes me think that we [could] use a nanomanufacturing approach to grow stem cells. We could mimic feeder cells’ nanotopology with 3-D printing techniques and skip using feeder cells altogether in the future.”
Cancer rate doubles in HCV patients
tissue with active HCV
Photo: Sutter Health
VIENNA, AUSTRIA—A 5-year retrospective study has shown that the cancer rate in patients with hepatitis C virus (HCV) is about double that for people without HCV, even when liver cancer is excluded.
And when liver cancer is included, the rate increases to 2.5 times higher in people with HCV.
Researchers presented these findings at the International Liver Congress 2015 as abstract 0058.
The team reviewed patient records from 2008 to 2012 at Kaiser Permanente Southern California, recording all cancer diagnoses in patients 18 years or older with or without HCV.
During the 5-year time period, there were 145,210 patient years in the HCV cohort and 13,948,826 patient years in the non-HCV cohort.
The mean age at cancer diagnosis was 61.8 in the HCV cohort and 63.5 in the non-HCV cohort.
Researchers recorded 2213 cancer diagnoses in the HCV cohort (1524/100,000). This number decreased to 1654 when they excluded liver cancer (1139/100,000).
In the non-HCV cohort, they recorded 84,419 cancer diagnoses (605/100,000), which decreased to 83,795 when liver cancer was excluded (601/100,000).
Cancer types known to be associated with HCV include non-Hodgkin lymphoma (NHL), renal and prostate cancers, and liver cancer.
NHL occurred 3.63 times more frequently in patients with HCV than in those without HCV, and myeloma occurred 2.93 times more frequently.
Renal cancer occurred 3.27 times and prostate cancer 1.98 times more frequently in patients with HCV than in those without.
“The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers,” said senior study author Lisa Nyberg, MD, MPH, of Kaiser Permanente.
“These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer.”
However, she added that the findings “must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results.”
tissue with active HCV
Photo: Sutter Health
VIENNA, AUSTRIA—A 5-year retrospective study has shown that the cancer rate in patients with hepatitis C virus (HCV) is about double that for people without HCV, even when liver cancer is excluded.
And when liver cancer is included, the rate increases to 2.5 times higher in people with HCV.
Researchers presented these findings at the International Liver Congress 2015 as abstract 0058.
The team reviewed patient records from 2008 to 2012 at Kaiser Permanente Southern California, recording all cancer diagnoses in patients 18 years or older with or without HCV.
During the 5-year time period, there were 145,210 patient years in the HCV cohort and 13,948,826 patient years in the non-HCV cohort.
The mean age at cancer diagnosis was 61.8 in the HCV cohort and 63.5 in the non-HCV cohort.
Researchers recorded 2213 cancer diagnoses in the HCV cohort (1524/100,000). This number decreased to 1654 when they excluded liver cancer (1139/100,000).
In the non-HCV cohort, they recorded 84,419 cancer diagnoses (605/100,000), which decreased to 83,795 when liver cancer was excluded (601/100,000).
Cancer types known to be associated with HCV include non-Hodgkin lymphoma (NHL), renal and prostate cancers, and liver cancer.
NHL occurred 3.63 times more frequently in patients with HCV than in those without HCV, and myeloma occurred 2.93 times more frequently.
Renal cancer occurred 3.27 times and prostate cancer 1.98 times more frequently in patients with HCV than in those without.
“The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers,” said senior study author Lisa Nyberg, MD, MPH, of Kaiser Permanente.
“These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer.”
However, she added that the findings “must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results.”
tissue with active HCV
Photo: Sutter Health
VIENNA, AUSTRIA—A 5-year retrospective study has shown that the cancer rate in patients with hepatitis C virus (HCV) is about double that for people without HCV, even when liver cancer is excluded.
And when liver cancer is included, the rate increases to 2.5 times higher in people with HCV.
Researchers presented these findings at the International Liver Congress 2015 as abstract 0058.
The team reviewed patient records from 2008 to 2012 at Kaiser Permanente Southern California, recording all cancer diagnoses in patients 18 years or older with or without HCV.
During the 5-year time period, there were 145,210 patient years in the HCV cohort and 13,948,826 patient years in the non-HCV cohort.
The mean age at cancer diagnosis was 61.8 in the HCV cohort and 63.5 in the non-HCV cohort.
Researchers recorded 2213 cancer diagnoses in the HCV cohort (1524/100,000). This number decreased to 1654 when they excluded liver cancer (1139/100,000).
In the non-HCV cohort, they recorded 84,419 cancer diagnoses (605/100,000), which decreased to 83,795 when liver cancer was excluded (601/100,000).
Cancer types known to be associated with HCV include non-Hodgkin lymphoma (NHL), renal and prostate cancers, and liver cancer.
NHL occurred 3.63 times more frequently in patients with HCV than in those without HCV, and myeloma occurred 2.93 times more frequently.
Renal cancer occurred 3.27 times and prostate cancer 1.98 times more frequently in patients with HCV than in those without.
“The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers,” said senior study author Lisa Nyberg, MD, MPH, of Kaiser Permanente.
“These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer.”
However, she added that the findings “must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results.”
First spray-dried fibrin sealant approved by FDA
Photo by Piotr Bodzek
The US Food and Drug Administration (FDA) has approved the first spray-dried fibrin sealant to help control bleeding during surgery.
The agency approved Raplixa (formerly known as Fibrocaps) for use in adults to control bleeding from small blood vessels when standard surgical techniques are ineffective or impractical.
The standard techniques include suture, ligature, or cautery.
Raplixa contains fibrinogen and thrombin, proteins found in human plasma. When the surgical team applies Raplixa to the bleeding site, the sealant dissolves in the blood, and the fibrinogen and thrombin proteins react, resulting in the formation of blood clots.
The protein components are individually purified using a manufacturing process that includes virus inactivation and removal steps to help reduce the risk for the transmission of blood-borne viruses. The fibrin sealant components are then spray-dried, blended, and packaged in a vial.
Raplixa can be applied directly from the original product vial or by spraying it with a delivery device. Raplixa is used in conjunction with an absorbable gelatin sponge.
“The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial,” said Karen Midthun, MD, of the FDA’s Center for Biologics Evaluation and Research.
“This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature.”
Raplixa was approved for use in the European Union in March, based on the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Phase 3 trial
The FDA approved Raplixa based on data from the FINISH-3 trial, a randomized, single-blind, controlled, phase 3 study of 719 patients undergoing spinal surgery (n=183), hepatic resection (n=180), vascular surgery (n=175), or soft tissue dissection (n=181) in 4 countries over 11 months.
As reported in the Journal of the American College of Surgeons, adults with mild or moderate surgical bleeding were randomized to recieve Raplixa or the gelatin sponge. Researchers recorded the time to hemostasis over 5 minutes within each surgical indication.
Four hundred and eighty patients were treated with Raplixa, and 239 were treated with the gelatin sponge. Surgeons used the spray device in 53% of Raplixa procedures.
Raplixa used in conjunction with the gelatin sponge significantly reduced time to hemostasis compared to the gelatin sponge alone (P<0.001 for each of the 4 sugical indications).
Raplixa also significantly reduced median time to hemostasis for each indication (P<0.0001).
Adverse events were similar between the treatment arms. The most commonly reported adverse reactions were surgical pain, nausea, constipation, fever, and decreased blood pressure.
Two percent of Raplixa-treated patients developed non-neutralizing anti-thrombin antibodies, as did 3% of patients treated with the gelatin sponge.
Raplixa is manufactured by ProFibrix BV, a wholly owned subsidiary of The Medicines Company, based in Parsippany, New Jersey.
Photo by Piotr Bodzek
The US Food and Drug Administration (FDA) has approved the first spray-dried fibrin sealant to help control bleeding during surgery.
The agency approved Raplixa (formerly known as Fibrocaps) for use in adults to control bleeding from small blood vessels when standard surgical techniques are ineffective or impractical.
The standard techniques include suture, ligature, or cautery.
Raplixa contains fibrinogen and thrombin, proteins found in human plasma. When the surgical team applies Raplixa to the bleeding site, the sealant dissolves in the blood, and the fibrinogen and thrombin proteins react, resulting in the formation of blood clots.
The protein components are individually purified using a manufacturing process that includes virus inactivation and removal steps to help reduce the risk for the transmission of blood-borne viruses. The fibrin sealant components are then spray-dried, blended, and packaged in a vial.
Raplixa can be applied directly from the original product vial or by spraying it with a delivery device. Raplixa is used in conjunction with an absorbable gelatin sponge.
“The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial,” said Karen Midthun, MD, of the FDA’s Center for Biologics Evaluation and Research.
“This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature.”
Raplixa was approved for use in the European Union in March, based on the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Phase 3 trial
The FDA approved Raplixa based on data from the FINISH-3 trial, a randomized, single-blind, controlled, phase 3 study of 719 patients undergoing spinal surgery (n=183), hepatic resection (n=180), vascular surgery (n=175), or soft tissue dissection (n=181) in 4 countries over 11 months.
As reported in the Journal of the American College of Surgeons, adults with mild or moderate surgical bleeding were randomized to recieve Raplixa or the gelatin sponge. Researchers recorded the time to hemostasis over 5 minutes within each surgical indication.
Four hundred and eighty patients were treated with Raplixa, and 239 were treated with the gelatin sponge. Surgeons used the spray device in 53% of Raplixa procedures.
Raplixa used in conjunction with the gelatin sponge significantly reduced time to hemostasis compared to the gelatin sponge alone (P<0.001 for each of the 4 sugical indications).
Raplixa also significantly reduced median time to hemostasis for each indication (P<0.0001).
Adverse events were similar between the treatment arms. The most commonly reported adverse reactions were surgical pain, nausea, constipation, fever, and decreased blood pressure.
Two percent of Raplixa-treated patients developed non-neutralizing anti-thrombin antibodies, as did 3% of patients treated with the gelatin sponge.
Raplixa is manufactured by ProFibrix BV, a wholly owned subsidiary of The Medicines Company, based in Parsippany, New Jersey.
Photo by Piotr Bodzek
The US Food and Drug Administration (FDA) has approved the first spray-dried fibrin sealant to help control bleeding during surgery.
The agency approved Raplixa (formerly known as Fibrocaps) for use in adults to control bleeding from small blood vessels when standard surgical techniques are ineffective or impractical.
The standard techniques include suture, ligature, or cautery.
Raplixa contains fibrinogen and thrombin, proteins found in human plasma. When the surgical team applies Raplixa to the bleeding site, the sealant dissolves in the blood, and the fibrinogen and thrombin proteins react, resulting in the formation of blood clots.
The protein components are individually purified using a manufacturing process that includes virus inactivation and removal steps to help reduce the risk for the transmission of blood-borne viruses. The fibrin sealant components are then spray-dried, blended, and packaged in a vial.
Raplixa can be applied directly from the original product vial or by spraying it with a delivery device. Raplixa is used in conjunction with an absorbable gelatin sponge.
“The spray-drying process used to manufacture Raplixa produces dried powders that can be combined into a single vial,” said Karen Midthun, MD, of the FDA’s Center for Biologics Evaluation and Research.
“This eliminates the need to combine the fibrinogen and thrombin before use and allows the product to be stored at room temperature.”
Raplixa was approved for use in the European Union in March, based on the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Phase 3 trial
The FDA approved Raplixa based on data from the FINISH-3 trial, a randomized, single-blind, controlled, phase 3 study of 719 patients undergoing spinal surgery (n=183), hepatic resection (n=180), vascular surgery (n=175), or soft tissue dissection (n=181) in 4 countries over 11 months.
As reported in the Journal of the American College of Surgeons, adults with mild or moderate surgical bleeding were randomized to recieve Raplixa or the gelatin sponge. Researchers recorded the time to hemostasis over 5 minutes within each surgical indication.
Four hundred and eighty patients were treated with Raplixa, and 239 were treated with the gelatin sponge. Surgeons used the spray device in 53% of Raplixa procedures.
Raplixa used in conjunction with the gelatin sponge significantly reduced time to hemostasis compared to the gelatin sponge alone (P<0.001 for each of the 4 sugical indications).
Raplixa also significantly reduced median time to hemostasis for each indication (P<0.0001).
Adverse events were similar between the treatment arms. The most commonly reported adverse reactions were surgical pain, nausea, constipation, fever, and decreased blood pressure.
Two percent of Raplixa-treated patients developed non-neutralizing anti-thrombin antibodies, as did 3% of patients treated with the gelatin sponge.
Raplixa is manufactured by ProFibrix BV, a wholly owned subsidiary of The Medicines Company, based in Parsippany, New Jersey.
Targeting receptors to better treat AML
Photo courtesy of UT
Southwestern Medical Center
Preclinical research suggests that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are important for the development of acute myeloid leukemia (AML).
“Although counterintuitive, this result is consistent with the generally immune-suppressive and, thus, tumor-promoting roles of inhibitory receptors in the immune system,” said Chengcheng Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.
“These findings suggest that blocking ITIM-receptor signaling in combination with conventional therapies may represent a novel strategy for AML treatment.”
Dr Zhang and his colleagues reported their findings in Nature Cell Biology.
The team focused mainly on an ITIM-containing receptor called LAIR1. They found that deleting LAIR1 abolished leukemia in several different mouse models, without affecting normal hematopoiesis.
The investigators also identified a pathway that sustains the survival and self-renewal of AML cells, the mechanism by which LAIR1 supports AML development.
They said LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signaling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. And the LAIR1–SHP-1–CAMK1–CREB pathway sustains AML stem cells.
So the investigators believe that inhibiting the signaling initiated by LAIR1 and other ITIM-containing receptors could help us treat AML more effectively.
“Our study suggests that current treatment options, including chemotherapy, may not efficiently target cancer stem cells because these inhibitory receptors enable the leukemia stem cells to survive conventional therapies, eventually resulting in tumor relapse,” Dr Zhang said.
“The blockade of ITIM-receptor signaling may prove to be a novel, effective strategy for elimination of leukemia stem cells and lead to complete remission in patients.”
Photo courtesy of UT
Southwestern Medical Center
Preclinical research suggests that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are important for the development of acute myeloid leukemia (AML).
“Although counterintuitive, this result is consistent with the generally immune-suppressive and, thus, tumor-promoting roles of inhibitory receptors in the immune system,” said Chengcheng Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.
“These findings suggest that blocking ITIM-receptor signaling in combination with conventional therapies may represent a novel strategy for AML treatment.”
Dr Zhang and his colleagues reported their findings in Nature Cell Biology.
The team focused mainly on an ITIM-containing receptor called LAIR1. They found that deleting LAIR1 abolished leukemia in several different mouse models, without affecting normal hematopoiesis.
The investigators also identified a pathway that sustains the survival and self-renewal of AML cells, the mechanism by which LAIR1 supports AML development.
They said LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signaling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. And the LAIR1–SHP-1–CAMK1–CREB pathway sustains AML stem cells.
So the investigators believe that inhibiting the signaling initiated by LAIR1 and other ITIM-containing receptors could help us treat AML more effectively.
“Our study suggests that current treatment options, including chemotherapy, may not efficiently target cancer stem cells because these inhibitory receptors enable the leukemia stem cells to survive conventional therapies, eventually resulting in tumor relapse,” Dr Zhang said.
“The blockade of ITIM-receptor signaling may prove to be a novel, effective strategy for elimination of leukemia stem cells and lead to complete remission in patients.”
Photo courtesy of UT
Southwestern Medical Center
Preclinical research suggests that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are important for the development of acute myeloid leukemia (AML).
“Although counterintuitive, this result is consistent with the generally immune-suppressive and, thus, tumor-promoting roles of inhibitory receptors in the immune system,” said Chengcheng Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.
“These findings suggest that blocking ITIM-receptor signaling in combination with conventional therapies may represent a novel strategy for AML treatment.”
Dr Zhang and his colleagues reported their findings in Nature Cell Biology.
The team focused mainly on an ITIM-containing receptor called LAIR1. They found that deleting LAIR1 abolished leukemia in several different mouse models, without affecting normal hematopoiesis.
The investigators also identified a pathway that sustains the survival and self-renewal of AML cells, the mechanism by which LAIR1 supports AML development.
They said LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signaling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. And the LAIR1–SHP-1–CAMK1–CREB pathway sustains AML stem cells.
So the investigators believe that inhibiting the signaling initiated by LAIR1 and other ITIM-containing receptors could help us treat AML more effectively.
“Our study suggests that current treatment options, including chemotherapy, may not efficiently target cancer stem cells because these inhibitory receptors enable the leukemia stem cells to survive conventional therapies, eventually resulting in tumor relapse,” Dr Zhang said.
“The blockade of ITIM-receptor signaling may prove to be a novel, effective strategy for elimination of leukemia stem cells and lead to complete remission in patients.”
Vigorous physical activity may lower risk of NHL
Photo by Shannon E. Renfroe
People who regularly engage in vigorous physical activity throughout their lifetime may have a lower risk of developing non-Hodgkin lymphoma (NHL), according to research published in Cancer Epidemiology, Biomarkers & Prevention.
“We know that being physically active reduces the risk of colon cancer and breast cancer, and also leads to a range of other physical and mental health benefits,” said study author Terry Boyle, PhD, of the University of British Columbia in Vancouver, Canada.
“Our findings suggest that people who do vigorous physical activity may also have a lower risk for NHL.”
Dr Boyle and his colleagues used data from a case-control study conducted between 2000 and 2004 in British Columbia. The team analyzed 749 NHL patients and 818 control subjects matched for age, gender, and residential location.
Study subjects recorded information on demographics and various risk factors for NHL, including lifetime recreational physical activity, on a questionnaire. Participants were asked to record the average number of days per week and average number of hours per day they performed mild, moderate, or vigorous physical activity for each decade of life.
The researchers defined “mild” activities as those that increase heart and breathing rates above resting level, “moderate” activities as those that increase heart rate moderately, and “vigorous” activities as those that increase breathing and heart rates to a high level. Mild and moderate activity were ultimately combined into a single category.
The team assigned a metabolic-equivalent (MET) value to the different types of physical activity.
Then, to assess the association between lifetime physical activity and NHL risk, the researchers calculated the average MET-hours per week over a lifetime for total physical activity, moderate-intensity activity, and vigorous-intensity activity. Finally, they classified participants into quartiles.
Participants who engaged in the most vigorously intense physical activity throughout their lifetime were classified in the second, third, and fourth quartiles. These subjects had about a 25% to 30% lower risk for NHL when compared to participants in the lowest (first) quartile of vigorously intense physical activity.
The adjusted odds ratio was 0.69 for the second quartile, 0.68 for the third, and 0.75 for the fourth (PTrend=0.072).
There was an inverse association between lifetime vigorous-intensity physical activity and overall NHL risk in males and females, as well as for all NHL subtypes. Furthermore, vigorous physical activity did not confer a greater benefit for any specific age group.
The researchers found no association between total lifetime physical activity and NHL risk or lifetime moderate-intensity physical activity and NHL risk.
Despite these results, Dr Boyle said there isn’t enough research on this topic to confirm that being physically active reduces the risk of NHL.
“So we are planning to pool data from several studies to investigate this topic further,” he said. “We know that different types of NHL may have different risk factors, so we are also planning to investigate whether physical activity influences the risk for different types of NHL in different ways.”
Photo by Shannon E. Renfroe
People who regularly engage in vigorous physical activity throughout their lifetime may have a lower risk of developing non-Hodgkin lymphoma (NHL), according to research published in Cancer Epidemiology, Biomarkers & Prevention.
“We know that being physically active reduces the risk of colon cancer and breast cancer, and also leads to a range of other physical and mental health benefits,” said study author Terry Boyle, PhD, of the University of British Columbia in Vancouver, Canada.
“Our findings suggest that people who do vigorous physical activity may also have a lower risk for NHL.”
Dr Boyle and his colleagues used data from a case-control study conducted between 2000 and 2004 in British Columbia. The team analyzed 749 NHL patients and 818 control subjects matched for age, gender, and residential location.
Study subjects recorded information on demographics and various risk factors for NHL, including lifetime recreational physical activity, on a questionnaire. Participants were asked to record the average number of days per week and average number of hours per day they performed mild, moderate, or vigorous physical activity for each decade of life.
The researchers defined “mild” activities as those that increase heart and breathing rates above resting level, “moderate” activities as those that increase heart rate moderately, and “vigorous” activities as those that increase breathing and heart rates to a high level. Mild and moderate activity were ultimately combined into a single category.
The team assigned a metabolic-equivalent (MET) value to the different types of physical activity.
Then, to assess the association between lifetime physical activity and NHL risk, the researchers calculated the average MET-hours per week over a lifetime for total physical activity, moderate-intensity activity, and vigorous-intensity activity. Finally, they classified participants into quartiles.
Participants who engaged in the most vigorously intense physical activity throughout their lifetime were classified in the second, third, and fourth quartiles. These subjects had about a 25% to 30% lower risk for NHL when compared to participants in the lowest (first) quartile of vigorously intense physical activity.
The adjusted odds ratio was 0.69 for the second quartile, 0.68 for the third, and 0.75 for the fourth (PTrend=0.072).
There was an inverse association between lifetime vigorous-intensity physical activity and overall NHL risk in males and females, as well as for all NHL subtypes. Furthermore, vigorous physical activity did not confer a greater benefit for any specific age group.
The researchers found no association between total lifetime physical activity and NHL risk or lifetime moderate-intensity physical activity and NHL risk.
Despite these results, Dr Boyle said there isn’t enough research on this topic to confirm that being physically active reduces the risk of NHL.
“So we are planning to pool data from several studies to investigate this topic further,” he said. “We know that different types of NHL may have different risk factors, so we are also planning to investigate whether physical activity influences the risk for different types of NHL in different ways.”
Photo by Shannon E. Renfroe
People who regularly engage in vigorous physical activity throughout their lifetime may have a lower risk of developing non-Hodgkin lymphoma (NHL), according to research published in Cancer Epidemiology, Biomarkers & Prevention.
“We know that being physically active reduces the risk of colon cancer and breast cancer, and also leads to a range of other physical and mental health benefits,” said study author Terry Boyle, PhD, of the University of British Columbia in Vancouver, Canada.
“Our findings suggest that people who do vigorous physical activity may also have a lower risk for NHL.”
Dr Boyle and his colleagues used data from a case-control study conducted between 2000 and 2004 in British Columbia. The team analyzed 749 NHL patients and 818 control subjects matched for age, gender, and residential location.
Study subjects recorded information on demographics and various risk factors for NHL, including lifetime recreational physical activity, on a questionnaire. Participants were asked to record the average number of days per week and average number of hours per day they performed mild, moderate, or vigorous physical activity for each decade of life.
The researchers defined “mild” activities as those that increase heart and breathing rates above resting level, “moderate” activities as those that increase heart rate moderately, and “vigorous” activities as those that increase breathing and heart rates to a high level. Mild and moderate activity were ultimately combined into a single category.
The team assigned a metabolic-equivalent (MET) value to the different types of physical activity.
Then, to assess the association between lifetime physical activity and NHL risk, the researchers calculated the average MET-hours per week over a lifetime for total physical activity, moderate-intensity activity, and vigorous-intensity activity. Finally, they classified participants into quartiles.
Participants who engaged in the most vigorously intense physical activity throughout their lifetime were classified in the second, third, and fourth quartiles. These subjects had about a 25% to 30% lower risk for NHL when compared to participants in the lowest (first) quartile of vigorously intense physical activity.
The adjusted odds ratio was 0.69 for the second quartile, 0.68 for the third, and 0.75 for the fourth (PTrend=0.072).
There was an inverse association between lifetime vigorous-intensity physical activity and overall NHL risk in males and females, as well as for all NHL subtypes. Furthermore, vigorous physical activity did not confer a greater benefit for any specific age group.
The researchers found no association between total lifetime physical activity and NHL risk or lifetime moderate-intensity physical activity and NHL risk.
Despite these results, Dr Boyle said there isn’t enough research on this topic to confirm that being physically active reduces the risk of NHL.
“So we are planning to pool data from several studies to investigate this topic further,” he said. “We know that different types of NHL may have different risk factors, so we are also planning to investigate whether physical activity influences the risk for different types of NHL in different ways.”
Symptoms confer higher-than-expected risk of HL, NHL
Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.
These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.
Both studies were published in the British Journal of General Practice.
“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.
“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”
The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.
The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).
In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.
The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).
Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.
Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.
Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.
“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”
Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.
These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.
Both studies were published in the British Journal of General Practice.
“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.
“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”
The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.
The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).
In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.
The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).
Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.
Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.
Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.
“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”
Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.
These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.
Both studies were published in the British Journal of General Practice.
“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.
“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”
The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.
The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).
In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.
The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).
Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.
Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.
Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.
“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”
Artificial blood vessels give way to the real thing
biocompatible polymer
Photo courtesy of Vienna
University of Technology
Scientists have created implantable artificial blood vessels using a newly developed polymer that is biodegradable.
In experiments with rats, these thin-walled vascular grafts were replaced by endogenous material, ultimately leaving natural, fully functional blood vessels in their place.
Furthermore, 6 months after the artificial vessels were implanted, none of the animals had experienced thromboses, inflammation, or aneurysms.
Helga Bergmeister, MD, DVM, PhD, of the Medical University of Vienna in Austria, and her colleagues conducted this research and described the results in Acta Biomaterialia.
To create artificial blood vessels that are compatible with body tissue, the researchers developed a new polymer—thermoplastic polyurethane.
“By selecting very specific molecular building blocks, we have succeeded in synthesizing a polymer with the desired properties,” said Robert Liska, PhD, of the Vienna University of Technology.
To produce the grafts, the researchers spun polymer solutions in an electrical field to form very fine threads and wound these threads onto a spool.
“The wall of these artificial blood vessels is very similar to that of natural ones,” said Heinrich Schima, PhD, of the Medical University of Vienna.
The polymer fabric is slightly porous. So, initially, it allows a small amount of blood to seep through, which enriches the wall with growth factors. And this encourages the migration of endogenous cells.
The researchers implanted these artificial blood vessels in rats and found them to be safe and functional long-term.
“The rats’ blood vessels were examined 6 months after insertion of the vascular prostheses,” Dr Bergmeister said.
“We did not find any aneurysms, thrombosis, or inflammation. Endogenous cells had colonized the vascular prostheses and turned the artificial constructs into natural body tissue.”
In fact, natural body tissue regrew much faster than expected.
The researchers said their thin-walled grafts “offer a new and desirable form of biodegradable vascular implant.”
biocompatible polymer
Photo courtesy of Vienna
University of Technology
Scientists have created implantable artificial blood vessels using a newly developed polymer that is biodegradable.
In experiments with rats, these thin-walled vascular grafts were replaced by endogenous material, ultimately leaving natural, fully functional blood vessels in their place.
Furthermore, 6 months after the artificial vessels were implanted, none of the animals had experienced thromboses, inflammation, or aneurysms.
Helga Bergmeister, MD, DVM, PhD, of the Medical University of Vienna in Austria, and her colleagues conducted this research and described the results in Acta Biomaterialia.
To create artificial blood vessels that are compatible with body tissue, the researchers developed a new polymer—thermoplastic polyurethane.
“By selecting very specific molecular building blocks, we have succeeded in synthesizing a polymer with the desired properties,” said Robert Liska, PhD, of the Vienna University of Technology.
To produce the grafts, the researchers spun polymer solutions in an electrical field to form very fine threads and wound these threads onto a spool.
“The wall of these artificial blood vessels is very similar to that of natural ones,” said Heinrich Schima, PhD, of the Medical University of Vienna.
The polymer fabric is slightly porous. So, initially, it allows a small amount of blood to seep through, which enriches the wall with growth factors. And this encourages the migration of endogenous cells.
The researchers implanted these artificial blood vessels in rats and found them to be safe and functional long-term.
“The rats’ blood vessels were examined 6 months after insertion of the vascular prostheses,” Dr Bergmeister said.
“We did not find any aneurysms, thrombosis, or inflammation. Endogenous cells had colonized the vascular prostheses and turned the artificial constructs into natural body tissue.”
In fact, natural body tissue regrew much faster than expected.
The researchers said their thin-walled grafts “offer a new and desirable form of biodegradable vascular implant.”
biocompatible polymer
Photo courtesy of Vienna
University of Technology
Scientists have created implantable artificial blood vessels using a newly developed polymer that is biodegradable.
In experiments with rats, these thin-walled vascular grafts were replaced by endogenous material, ultimately leaving natural, fully functional blood vessels in their place.
Furthermore, 6 months after the artificial vessels were implanted, none of the animals had experienced thromboses, inflammation, or aneurysms.
Helga Bergmeister, MD, DVM, PhD, of the Medical University of Vienna in Austria, and her colleagues conducted this research and described the results in Acta Biomaterialia.
To create artificial blood vessels that are compatible with body tissue, the researchers developed a new polymer—thermoplastic polyurethane.
“By selecting very specific molecular building blocks, we have succeeded in synthesizing a polymer with the desired properties,” said Robert Liska, PhD, of the Vienna University of Technology.
To produce the grafts, the researchers spun polymer solutions in an electrical field to form very fine threads and wound these threads onto a spool.
“The wall of these artificial blood vessels is very similar to that of natural ones,” said Heinrich Schima, PhD, of the Medical University of Vienna.
The polymer fabric is slightly porous. So, initially, it allows a small amount of blood to seep through, which enriches the wall with growth factors. And this encourages the migration of endogenous cells.
The researchers implanted these artificial blood vessels in rats and found them to be safe and functional long-term.
“The rats’ blood vessels were examined 6 months after insertion of the vascular prostheses,” Dr Bergmeister said.
“We did not find any aneurysms, thrombosis, or inflammation. Endogenous cells had colonized the vascular prostheses and turned the artificial constructs into natural body tissue.”
In fact, natural body tissue regrew much faster than expected.
The researchers said their thin-walled grafts “offer a new and desirable form of biodegradable vascular implant.”
Susceptibility to 2nd cancers in WM/LPL survivors
PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.
Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.
The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.
The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.
Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).
The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).
Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.
“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”
Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).
This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).
Hematologic malignancies
WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.
Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.
“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”
The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).
“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”
She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.
In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.
Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).
Solid tumors
WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.
The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).
“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.
She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.
“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”
Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.
Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.
PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.
Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.
The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.
The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.
Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).
The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).
Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.
“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”
Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).
This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).
Hematologic malignancies
WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.
Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.
“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”
The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).
“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”
She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.
In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.
Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).
Solid tumors
WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.
The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).
“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.
She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.
“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”
Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.
Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.
PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.
Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.
The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.
The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.
Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).
The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).
Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.
“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”
Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).
This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).
Hematologic malignancies
WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.
Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.
“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”
The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).
“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”
She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.
In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.
Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).
Solid tumors
WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.
The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).
“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.
She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.
“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”
Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.
Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.
Enzyme could enable creation of universal blood type
Photo by Elise Amendola
Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.
The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.
The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.
David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.
“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.
To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.
The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.
Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.
In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.
The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.
The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.
“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”
Photo by Elise Amendola
Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.
The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.
The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.
David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.
“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.
To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.
The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.
Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.
In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.
The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.
The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.
“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”
Photo by Elise Amendola
Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.
The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.
The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.
David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.
“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.
To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.
The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.
Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.
In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.
The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.
The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.
“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”