NEW YORK (Reuters Health) - Lipid-lowering therapy, consisting almost entirely of statins, substantially lowered the risk of cardiovascular disease (CVD) and cardiovascular death in individuals with type 1 diabetes without a history of CVD, according to a new study.

Among more than 24,000 Swedish patients with type 1 diabetes, over a mean follow-up of six years, primary prevention with lipid-lowering therapy (LLT) reduced the incidence of cardiovascular death, all-cause death, stroke, coronary heart disease, and acute myocardial infarction.

The risk of cardiovascular death was reduced by 40%, while the reductions for acute MI and coronary heart disease were 22% and 15%, respectively, according to an article online on April 18 in Diabetes Care.

In email to Reuters Health, corresponding author Dr. Christel Hero, of the Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden, emphasized that "individuals with type 1 diabetes are at enhanced risk for CVD compared to the general population."

The study encompassed 24,230 individuals with type 1 diabetes (mean age 39.4 years): 5,387 treated with lipid-lowering medication and 18,843 untreated. In 97% of cases, LLT was with statins.

Hazard ratios for treated versus untreated participants were significant for all outcomes: cardiovascular death, 0.60; all-cause death, 0.56; fatal/nonfatal stroke, 0.56; fatal/nonfatal acute myocardial infarction, 0.78; and fatal/nonfatal coronary heart disease 0.85. Hazard ratios in a one-to-one matched cohort with 4,025 treated and 4,025 untreated individuals were significant only for all-cause death (0.74).

"Our study shows convincing effects of LLT in preventing all cardiovascular endpoints, even if the effect on reducing cardiovascular morbidity, except for stroke, was lesser than the effect on cardiovascular death and all-cause death," the authors wrote.

This study, Dr. Urman said, supports the idea that essentially all type 1 diabetics should be taking statins (absent any contraindications).

NEW YORK (Reuters Health) - Lipid-lowering therapy, consisting almost entirely of statins, substantially lowered the risk of cardiovascular disease (CVD) and cardiovascular death in individuals with type 1 diabetes without a history of CVD, according to a new study.

Among more than 24,000 Swedish patients with type 1 diabetes, over a mean follow-up of six years, primary prevention with lipid-lowering therapy (LLT) reduced the incidence of cardiovascular death, all-cause death, stroke, coronary heart disease, and acute myocardial infarction.

The risk of cardiovascular death was reduced by 40%, while the reductions for acute MI and coronary heart disease were 22% and 15%, respectively, according to an article online on April 18 in Diabetes Care.

In email to Reuters Health, corresponding author Dr. Christel Hero, of the Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden, emphasized that "individuals with type 1 diabetes are at enhanced risk for CVD compared to the general population."

The study encompassed 24,230 individuals with type 1 diabetes (mean age 39.4 years): 5,387 treated with lipid-lowering medication and 18,843 untreated. In 97% of cases, LLT was with statins.

Hazard ratios for treated versus untreated participants were significant for all outcomes: cardiovascular death, 0.60; all-cause death, 0.56; fatal/nonfatal stroke, 0.56; fatal/nonfatal acute myocardial infarction, 0.78; and fatal/nonfatal coronary heart disease 0.85. Hazard ratios in a one-to-one matched cohort with 4,025 treated and 4,025 untreated individuals were significant only for all-cause death (0.74).

"Our study shows convincing effects of LLT in preventing all cardiovascular endpoints, even if the effect on reducing cardiovascular morbidity, except for stroke, was lesser than the effect on cardiovascular death and all-cause death," the authors wrote.

This study, Dr. Urman said, supports the idea that essentially all type 1 diabetics should be taking statins (absent any contraindications).

NEW YORK (Reuters Health) - Lipid-lowering therapy, consisting almost entirely of statins, substantially lowered the risk of cardiovascular disease (CVD) and cardiovascular death in individuals with type 1 diabetes without a history of CVD, according to a new study.

Among more than 24,000 Swedish patients with type 1 diabetes, over a mean follow-up of six years, primary prevention with lipid-lowering therapy (LLT) reduced the incidence of cardiovascular death, all-cause death, stroke, coronary heart disease, and acute myocardial infarction.

The risk of cardiovascular death was reduced by 40%, while the reductions for acute MI and coronary heart disease were 22% and 15%, respectively, according to an article online on April 18 in Diabetes Care.

In email to Reuters Health, corresponding author Dr. Christel Hero, of the Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden, emphasized that "individuals with type 1 diabetes are at enhanced risk for CVD compared to the general population."

The study encompassed 24,230 individuals with type 1 diabetes (mean age 39.4 years): 5,387 treated with lipid-lowering medication and 18,843 untreated. In 97% of cases, LLT was with statins.

Hazard ratios for treated versus untreated participants were significant for all outcomes: cardiovascular death, 0.60; all-cause death, 0.56; fatal/nonfatal stroke, 0.56; fatal/nonfatal acute myocardial infarction, 0.78; and fatal/nonfatal coronary heart disease 0.85. Hazard ratios in a one-to-one matched cohort with 4,025 treated and 4,025 untreated individuals were significant only for all-cause death (0.74).

"Our study shows convincing effects of LLT in preventing all cardiovascular endpoints, even if the effect on reducing cardiovascular morbidity, except for stroke, was lesser than the effect on cardiovascular death and all-cause death," the authors wrote.

This study, Dr. Urman said, supports the idea that essentially all type 1 diabetics should be taking statins (absent any contraindications).

Vial of heparin

ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.

The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.

The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.

These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).

The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.

The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.

“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.

“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”

Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.

Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.

By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).

Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).

Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).

“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”

BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.

Vial of heparin

ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.

The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.

The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.

These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).

The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.

The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.

“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.

“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”

Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.

Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.

By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).

Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).

Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).

“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”

BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.

Vial of heparin

ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.

The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.

The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.

These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).

The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.

The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.

“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.

“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”

Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.

Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.

By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).

Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).

Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).

“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”

BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Vials of drug

Photo by Bill Branson

Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.

The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.

However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.

BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.

Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.

Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.

Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.

Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.

Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.

Prescription medications

Photo courtesy of the CDC

SAN FRANCISCO—New research suggests patients with atrial fibrillation (AF) may benefit from receiving novel oral anticoagulants on an “as-needed” basis.

The study indicated that anticoagulant therapy guided by diligent pulse monitoring can be a safe and effective alternative to long-term anticoagulant therapy for lowering the overall risk of stroke in AF patients.

This finding was presented at the Heart Rhythm Society’s 37th Annual Scientific Session (abstract AB21-06).

The researchers studied 100 AF patients, ages 45 to 78, who had significant stroke risk. All patients had no AF recurrences during an extended period of telemetry monitoring before the study began.

Eighty-four patients had been ablated, 16 were being treated with drug therapy, and 3 had implanted devices that served as a quality control check.

Each patient was instructed to monitor his or her pulse—manually or by using a smartphone—twice a day and take an anticoagulant as needed. The patients were provided with novel oral anticoagulants and were instructed to start taking the medication if they suspected or detected an AF episode lasting longer than 1 hour.

“This kind of approach to anticoagulation therapy requires an open line of communication between the patient and the care team and calls for a specific type of patient,” said Monica Pammer, a physician assistant at the Hospital of the University of Pennsylvania in Philadelphia.

“We call them ‘highly motivated patients.’ These are patients who were actively seeking, preparing for, and are committed to the alternate treatment method, and who are informed about how to diligently and effectively monitor their pulse throughout the day.”

The researchers followed the patients for approximately 23 months.

During this time, 28 patients started taking an anticoagulant at least once for a suspected or detected AF episode, and 10 patients transitioned back to chronic oral anticoagulation therapy for recurrent AF.

None of the patients experienced a stroke or transient ischemic attack, but there was 1 mild bleeding incident that required medical attention.

“It is extremely common for patients with AF to seek treatment that does not involve the use of chronic oral anticoagulants therapy, as there are other risks associated with their long-term use,” said Francis E. Marchlinski, MD, of the University of Pennsylvania Health System.

“The goal of this study was to find a safe and effective treatment option, and our initial results support ‘as-needed’ blood thinners and pulse monitoring as the alternative.”

“While this is an observational study with a relatively small patient sample, further research is certainly needed to better understand alternate treatment options,” Pammer said. “And we stress that ‘as-needed’ blood thinners should not be considered unless the patient qualifies as highly motivated.”

Prescription medications

Photo courtesy of the CDC

SAN FRANCISCO—New research suggests patients with atrial fibrillation (AF) may benefit from receiving novel oral anticoagulants on an “as-needed” basis.

The study indicated that anticoagulant therapy guided by diligent pulse monitoring can be a safe and effective alternative to long-term anticoagulant therapy for lowering the overall risk of stroke in AF patients.

This finding was presented at the Heart Rhythm Society’s 37th Annual Scientific Session (abstract AB21-06).

The researchers studied 100 AF patients, ages 45 to 78, who had significant stroke risk. All patients had no AF recurrences during an extended period of telemetry monitoring before the study began.

Eighty-four patients had been ablated, 16 were being treated with drug therapy, and 3 had implanted devices that served as a quality control check.

Each patient was instructed to monitor his or her pulse—manually or by using a smartphone—twice a day and take an anticoagulant as needed. The patients were provided with novel oral anticoagulants and were instructed to start taking the medication if they suspected or detected an AF episode lasting longer than 1 hour.

“This kind of approach to anticoagulation therapy requires an open line of communication between the patient and the care team and calls for a specific type of patient,” said Monica Pammer, a physician assistant at the Hospital of the University of Pennsylvania in Philadelphia.

“We call them ‘highly motivated patients.’ These are patients who were actively seeking, preparing for, and are committed to the alternate treatment method, and who are informed about how to diligently and effectively monitor their pulse throughout the day.”

The researchers followed the patients for approximately 23 months.

During this time, 28 patients started taking an anticoagulant at least once for a suspected or detected AF episode, and 10 patients transitioned back to chronic oral anticoagulation therapy for recurrent AF.

None of the patients experienced a stroke or transient ischemic attack, but there was 1 mild bleeding incident that required medical attention.

“It is extremely common for patients with AF to seek treatment that does not involve the use of chronic oral anticoagulants therapy, as there are other risks associated with their long-term use,” said Francis E. Marchlinski, MD, of the University of Pennsylvania Health System.

“The goal of this study was to find a safe and effective treatment option, and our initial results support ‘as-needed’ blood thinners and pulse monitoring as the alternative.”

“While this is an observational study with a relatively small patient sample, further research is certainly needed to better understand alternate treatment options,” Pammer said. “And we stress that ‘as-needed’ blood thinners should not be considered unless the patient qualifies as highly motivated.”

Prescription medications

Photo courtesy of the CDC

SAN FRANCISCO—New research suggests patients with atrial fibrillation (AF) may benefit from receiving novel oral anticoagulants on an “as-needed” basis.

The study indicated that anticoagulant therapy guided by diligent pulse monitoring can be a safe and effective alternative to long-term anticoagulant therapy for lowering the overall risk of stroke in AF patients.

This finding was presented at the Heart Rhythm Society’s 37th Annual Scientific Session (abstract AB21-06).

The researchers studied 100 AF patients, ages 45 to 78, who had significant stroke risk. All patients had no AF recurrences during an extended period of telemetry monitoring before the study began.

Eighty-four patients had been ablated, 16 were being treated with drug therapy, and 3 had implanted devices that served as a quality control check.

Each patient was instructed to monitor his or her pulse—manually or by using a smartphone—twice a day and take an anticoagulant as needed. The patients were provided with novel oral anticoagulants and were instructed to start taking the medication if they suspected or detected an AF episode lasting longer than 1 hour.

“This kind of approach to anticoagulation therapy requires an open line of communication between the patient and the care team and calls for a specific type of patient,” said Monica Pammer, a physician assistant at the Hospital of the University of Pennsylvania in Philadelphia.

“We call them ‘highly motivated patients.’ These are patients who were actively seeking, preparing for, and are committed to the alternate treatment method, and who are informed about how to diligently and effectively monitor their pulse throughout the day.”

The researchers followed the patients for approximately 23 months.

During this time, 28 patients started taking an anticoagulant at least once for a suspected or detected AF episode, and 10 patients transitioned back to chronic oral anticoagulation therapy for recurrent AF.

None of the patients experienced a stroke or transient ischemic attack, but there was 1 mild bleeding incident that required medical attention.

“It is extremely common for patients with AF to seek treatment that does not involve the use of chronic oral anticoagulants therapy, as there are other risks associated with their long-term use,” said Francis E. Marchlinski, MD, of the University of Pennsylvania Health System.

“The goal of this study was to find a safe and effective treatment option, and our initial results support ‘as-needed’ blood thinners and pulse monitoring as the alternative.”

“While this is an observational study with a relatively small patient sample, further research is certainly needed to better understand alternate treatment options,” Pammer said. “And we stress that ‘as-needed’ blood thinners should not be considered unless the patient qualifies as highly motivated.”

Lab mouse

Preclinical research suggests synthetic peptides called minihepcidins could potentially treat beta-thalassemia and polycythemia vera (PV).

Investigators found that minihepcidin helped to restore normal levels of red blood cells (RBCs) and reduced spleen enlargement in mouse models of beta-thalassemia and PV.

Minihepcidin also controlled the accumulation of excess iron in the mice.

“It seems counterintuitive that one compound could treat two diseases that are quite different, but by restricting iron absorption, it also helps to normalize red blood cell levels in animals,” said study author Stefano Rivella, PhD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“If these preclinical results translate to humans, this could represent a new treatment for both disorders.”

Dr Rivella and his colleagues described the results in Blood.

The investigators used minihepcidins, modified versions of the naturally occurring hormone hepcidin, which regulates iron. Minihepcidins are smaller than the full-length hormone but have long-term stability and long-lasting biological activity when administered to animals.

Previous research showed that minihepcidin treatment can prevent iron overload in mouse models of hemochromatosis.

So Dr Rivella and his colleagues wanted to determine how minihepcidins affect beta-thalassemia and PV in mice separately engineered to model each disease.

The team found that, in young mice that modelled beta-thalassemia, minihepcidin treatment normalized RBC levels and relieved both anemia and iron overload.

In older mice, minihepcidin improved RBC production and did not interfere with a chelating drug used to remove excess iron deposits.

In mice expressing the orthologous JAK2 mutation causing human PV, minihepcidin normalized RBC production.

Because increased iron absorption in PV keeps RBC production in overdrive, when minihepcidin curtailed iron absorption, it lowered the abnormally high numbers of RBCs, which also reduced spleen enlargement.

Dr Rivella noted that if minihepcidins prove successful in clinical trials, they may provide an important tool in treating these blood disorders.

“In animals affected by beta-thalassemia, the compound blocks iron from getting into organs but doesn’t remove excess iron already in organs and tissues,” Dr Rivella said. “If minihepcidins are used in older patients, they would need to be combined with existing chelating drugs that remove the already-accumulated iron.”

However, he added that, in beta-thalassemia, providing minihepcidins in childhood might halt iron accumulation and prevent more severe adult disease.

In PV, minihepcidins may help normalize a patient’s RBC production but, as in beta-thalassemia, would not treat the underlying disease-causing mutations.

Merganser Biotech Inc. is developing minihepcidins as novel therapies for rare hematologic diseases. Merganser’s lead compound, M012, is now under evaluation in a phase 1 clinical program as a potential therapy for beta-thalassemia, low-risk myelodysplasia, PV, alpha-thalassemia, and sickle cell disease.

The company’s chief executive officer, Brian MacDonald, MB ChB, PhD, is a co-author of the current study. Dr Rivella is a paid consultant on Merganser Biotech’s clinical trial, owns restricted stocks in Merganser, and is a member of its scientific advisory board.

Lab mouse

Preclinical research suggests synthetic peptides called minihepcidins could potentially treat beta-thalassemia and polycythemia vera (PV).

Investigators found that minihepcidin helped to restore normal levels of red blood cells (RBCs) and reduced spleen enlargement in mouse models of beta-thalassemia and PV.

Minihepcidin also controlled the accumulation of excess iron in the mice.

“It seems counterintuitive that one compound could treat two diseases that are quite different, but by restricting iron absorption, it also helps to normalize red blood cell levels in animals,” said study author Stefano Rivella, PhD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“If these preclinical results translate to humans, this could represent a new treatment for both disorders.”

Dr Rivella and his colleagues described the results in Blood.

The investigators used minihepcidins, modified versions of the naturally occurring hormone hepcidin, which regulates iron. Minihepcidins are smaller than the full-length hormone but have long-term stability and long-lasting biological activity when administered to animals.

Previous research showed that minihepcidin treatment can prevent iron overload in mouse models of hemochromatosis.

So Dr Rivella and his colleagues wanted to determine how minihepcidins affect beta-thalassemia and PV in mice separately engineered to model each disease.

The team found that, in young mice that modelled beta-thalassemia, minihepcidin treatment normalized RBC levels and relieved both anemia and iron overload.

In older mice, minihepcidin improved RBC production and did not interfere with a chelating drug used to remove excess iron deposits.

In mice expressing the orthologous JAK2 mutation causing human PV, minihepcidin normalized RBC production.

Because increased iron absorption in PV keeps RBC production in overdrive, when minihepcidin curtailed iron absorption, it lowered the abnormally high numbers of RBCs, which also reduced spleen enlargement.

Dr Rivella noted that if minihepcidins prove successful in clinical trials, they may provide an important tool in treating these blood disorders.

“In animals affected by beta-thalassemia, the compound blocks iron from getting into organs but doesn’t remove excess iron already in organs and tissues,” Dr Rivella said. “If minihepcidins are used in older patients, they would need to be combined with existing chelating drugs that remove the already-accumulated iron.”

However, he added that, in beta-thalassemia, providing minihepcidins in childhood might halt iron accumulation and prevent more severe adult disease.

In PV, minihepcidins may help normalize a patient’s RBC production but, as in beta-thalassemia, would not treat the underlying disease-causing mutations.

Merganser Biotech Inc. is developing minihepcidins as novel therapies for rare hematologic diseases. Merganser’s lead compound, M012, is now under evaluation in a phase 1 clinical program as a potential therapy for beta-thalassemia, low-risk myelodysplasia, PV, alpha-thalassemia, and sickle cell disease.

The company’s chief executive officer, Brian MacDonald, MB ChB, PhD, is a co-author of the current study. Dr Rivella is a paid consultant on Merganser Biotech’s clinical trial, owns restricted stocks in Merganser, and is a member of its scientific advisory board.

Lab mouse

Preclinical research suggests synthetic peptides called minihepcidins could potentially treat beta-thalassemia and polycythemia vera (PV).

Investigators found that minihepcidin helped to restore normal levels of red blood cells (RBCs) and reduced spleen enlargement in mouse models of beta-thalassemia and PV.

Minihepcidin also controlled the accumulation of excess iron in the mice.

“It seems counterintuitive that one compound could treat two diseases that are quite different, but by restricting iron absorption, it also helps to normalize red blood cell levels in animals,” said study author Stefano Rivella, PhD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“If these preclinical results translate to humans, this could represent a new treatment for both disorders.”

Dr Rivella and his colleagues described the results in Blood.

The investigators used minihepcidins, modified versions of the naturally occurring hormone hepcidin, which regulates iron. Minihepcidins are smaller than the full-length hormone but have long-term stability and long-lasting biological activity when administered to animals.

Previous research showed that minihepcidin treatment can prevent iron overload in mouse models of hemochromatosis.

So Dr Rivella and his colleagues wanted to determine how minihepcidins affect beta-thalassemia and PV in mice separately engineered to model each disease.

The team found that, in young mice that modelled beta-thalassemia, minihepcidin treatment normalized RBC levels and relieved both anemia and iron overload.

In older mice, minihepcidin improved RBC production and did not interfere with a chelating drug used to remove excess iron deposits.

In mice expressing the orthologous JAK2 mutation causing human PV, minihepcidin normalized RBC production.

Because increased iron absorption in PV keeps RBC production in overdrive, when minihepcidin curtailed iron absorption, it lowered the abnormally high numbers of RBCs, which also reduced spleen enlargement.

Dr Rivella noted that if minihepcidins prove successful in clinical trials, they may provide an important tool in treating these blood disorders.

“In animals affected by beta-thalassemia, the compound blocks iron from getting into organs but doesn’t remove excess iron already in organs and tissues,” Dr Rivella said. “If minihepcidins are used in older patients, they would need to be combined with existing chelating drugs that remove the already-accumulated iron.”

However, he added that, in beta-thalassemia, providing minihepcidins in childhood might halt iron accumulation and prevent more severe adult disease.

In PV, minihepcidins may help normalize a patient’s RBC production but, as in beta-thalassemia, would not treat the underlying disease-causing mutations.

Merganser Biotech Inc. is developing minihepcidins as novel therapies for rare hematologic diseases. Merganser’s lead compound, M012, is now under evaluation in a phase 1 clinical program as a potential therapy for beta-thalassemia, low-risk myelodysplasia, PV, alpha-thalassemia, and sickle cell disease.

The company’s chief executive officer, Brian MacDonald, MB ChB, PhD, is a co-author of the current study. Dr Rivella is a paid consultant on Merganser Biotech’s clinical trial, owns restricted stocks in Merganser, and is a member of its scientific advisory board.

LOS ANGELES – Overall 5-year survival rates for anal cancer in the United States have steadily improved since the 1970s, but the incidence of disease continues to rise. In addition, African Americans with anal cancer have significantly and disproportionally lower 5-year survival rates, compared with whites.

Those are key findings from an analysis of Surveillance, Epidemiology and End Results (SEER) data that primary study author Dr. Marco Ferrara presented at the annual meeting of the American Society of Colon and Rectal Surgeons.

“Disparities in health-related outcomes for diseases such as cancer are unfortunately commonly observed,” Dr. Ferrara’s mentor and the senior study author Dr. Daniel I. Chu said in an interview in advance of the meeting. “African Americans in particular have higher cancer-specific death rates, higher rates of advanced cancer on initial diagnosis, and less frequent use of cancer screening tests. While our understanding of disparities continues to progress for the more common cancers (lung, breast, prostate, colorectal), comparatively fewer data are available for anal cancer. This gap in knowledge is important because anal cancer incidence has actually been increasing in the U.S. population over the past decades. While effective treatment is available, we asked if disparities exist in anal cancer.”

To find out, the researchers used the national SEER database to identify all patients with cancer of the anus, anal canal, and anorectum from 1973 to 1999 (Period 1; a total of 6,755 cases) and 2000 to 2012 (Period 2; a total of 18,027 cases) and stratified them by race. They determined the incidence, staging, and treatment provided for each group and used 2000 Census data to calculate the age-adjusted annual incidence of anal cancer. The primary outcome was 5-year survival.

More than half of patients (61%) were female, 86% were white, 10% were African American, and the remaining 4% were from other ethnic groups. Dr. Ferrara, who is a fourth-year surgery resident at Baptist Health System in Birmingham, Ala., reported that between Periods 1 and 2, the overall incidence of anal cancer increased from 1.1 to 1.8 cases per 100,000 individuals. The overall incidence was higher among African Americans, compared with whites (1.6 vs. 1.3 cases per 100,000 individuals, respectively). The incidence among African-American males was slightly higher, at 1.9 cases per 100,000 individuals.

The researchers found that nearly half of patients (48%) presented with localized disease, while 31% had regional disease. Between Periods 1 and 2 the proportion of patients who received any treatment for anal cancer increased from 63% to 74%. The use of radiation therapy increased from 61% to 72%, while the use of local excisions and abdominoperineal resections decreased from 60% to 45%. Overall, African Americans were more likely than whites to not undergo recommended surgery (9.8% vs. 8.7%, respectively) or to refuse recommended surgery (1.8% vs. 1.1%; P less than .05 for both associations).

Overall 5-year survival for anal cancer improved from 63% in Period 1 to 70% in Period 2 (P less than .05). However, African Americans had significantly lower 5-year survival rates, compared with whites in both time periods (53% vs. 64% in Period 1, and 62% vs. 71% in Period 2; P less than .05 for both associations).

“Health disparities exist in anal cancer with African Americans faring worse than Caucasian patients,” said Dr. Chu, who is a gastrointestinal surgeon at the University of Alabama at Birmingham. “While the etiologies for these disparities are unclear, anal cancer is a very treatable disease when caught early, regardless of race. Screening should be done for those at higher risk, such as patients with a family history of anal cancer, HIV, or HPV [human papillomavirus]. Ultimately, more research is needed to understand the factors driving these disparities at the patient, provider, and health care system level.”

He acknowledged certain limitations of the study, including its retrospective nature, the inability to assess the potential impact of education status and other social factors, and the generalizability of its findings, since SEER is limited to major cancer hospitals.

The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

LOS ANGELES – Overall 5-year survival rates for anal cancer in the United States have steadily improved since the 1970s, but the incidence of disease continues to rise. In addition, African Americans with anal cancer have significantly and disproportionally lower 5-year survival rates, compared with whites.

Those are key findings from an analysis of Surveillance, Epidemiology and End Results (SEER) data that primary study author Dr. Marco Ferrara presented at the annual meeting of the American Society of Colon and Rectal Surgeons.

“Disparities in health-related outcomes for diseases such as cancer are unfortunately commonly observed,” Dr. Ferrara’s mentor and the senior study author Dr. Daniel I. Chu said in an interview in advance of the meeting. “African Americans in particular have higher cancer-specific death rates, higher rates of advanced cancer on initial diagnosis, and less frequent use of cancer screening tests. While our understanding of disparities continues to progress for the more common cancers (lung, breast, prostate, colorectal), comparatively fewer data are available for anal cancer. This gap in knowledge is important because anal cancer incidence has actually been increasing in the U.S. population over the past decades. While effective treatment is available, we asked if disparities exist in anal cancer.”

To find out, the researchers used the national SEER database to identify all patients with cancer of the anus, anal canal, and anorectum from 1973 to 1999 (Period 1; a total of 6,755 cases) and 2000 to 2012 (Period 2; a total of 18,027 cases) and stratified them by race. They determined the incidence, staging, and treatment provided for each group and used 2000 Census data to calculate the age-adjusted annual incidence of anal cancer. The primary outcome was 5-year survival.

More than half of patients (61%) were female, 86% were white, 10% were African American, and the remaining 4% were from other ethnic groups. Dr. Ferrara, who is a fourth-year surgery resident at Baptist Health System in Birmingham, Ala., reported that between Periods 1 and 2, the overall incidence of anal cancer increased from 1.1 to 1.8 cases per 100,000 individuals. The overall incidence was higher among African Americans, compared with whites (1.6 vs. 1.3 cases per 100,000 individuals, respectively). The incidence among African-American males was slightly higher, at 1.9 cases per 100,000 individuals.

The researchers found that nearly half of patients (48%) presented with localized disease, while 31% had regional disease. Between Periods 1 and 2 the proportion of patients who received any treatment for anal cancer increased from 63% to 74%. The use of radiation therapy increased from 61% to 72%, while the use of local excisions and abdominoperineal resections decreased from 60% to 45%. Overall, African Americans were more likely than whites to not undergo recommended surgery (9.8% vs. 8.7%, respectively) or to refuse recommended surgery (1.8% vs. 1.1%; P less than .05 for both associations).

Overall 5-year survival for anal cancer improved from 63% in Period 1 to 70% in Period 2 (P less than .05). However, African Americans had significantly lower 5-year survival rates, compared with whites in both time periods (53% vs. 64% in Period 1, and 62% vs. 71% in Period 2; P less than .05 for both associations).

“Health disparities exist in anal cancer with African Americans faring worse than Caucasian patients,” said Dr. Chu, who is a gastrointestinal surgeon at the University of Alabama at Birmingham. “While the etiologies for these disparities are unclear, anal cancer is a very treatable disease when caught early, regardless of race. Screening should be done for those at higher risk, such as patients with a family history of anal cancer, HIV, or HPV [human papillomavirus]. Ultimately, more research is needed to understand the factors driving these disparities at the patient, provider, and health care system level.”

He acknowledged certain limitations of the study, including its retrospective nature, the inability to assess the potential impact of education status and other social factors, and the generalizability of its findings, since SEER is limited to major cancer hospitals.

The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

LOS ANGELES – Overall 5-year survival rates for anal cancer in the United States have steadily improved since the 1970s, but the incidence of disease continues to rise. In addition, African Americans with anal cancer have significantly and disproportionally lower 5-year survival rates, compared with whites.

Those are key findings from an analysis of Surveillance, Epidemiology and End Results (SEER) data that primary study author Dr. Marco Ferrara presented at the annual meeting of the American Society of Colon and Rectal Surgeons.

“Disparities in health-related outcomes for diseases such as cancer are unfortunately commonly observed,” Dr. Ferrara’s mentor and the senior study author Dr. Daniel I. Chu said in an interview in advance of the meeting. “African Americans in particular have higher cancer-specific death rates, higher rates of advanced cancer on initial diagnosis, and less frequent use of cancer screening tests. While our understanding of disparities continues to progress for the more common cancers (lung, breast, prostate, colorectal), comparatively fewer data are available for anal cancer. This gap in knowledge is important because anal cancer incidence has actually been increasing in the U.S. population over the past decades. While effective treatment is available, we asked if disparities exist in anal cancer.”

To find out, the researchers used the national SEER database to identify all patients with cancer of the anus, anal canal, and anorectum from 1973 to 1999 (Period 1; a total of 6,755 cases) and 2000 to 2012 (Period 2; a total of 18,027 cases) and stratified them by race. They determined the incidence, staging, and treatment provided for each group and used 2000 Census data to calculate the age-adjusted annual incidence of anal cancer. The primary outcome was 5-year survival.

More than half of patients (61%) were female, 86% were white, 10% were African American, and the remaining 4% were from other ethnic groups. Dr. Ferrara, who is a fourth-year surgery resident at Baptist Health System in Birmingham, Ala., reported that between Periods 1 and 2, the overall incidence of anal cancer increased from 1.1 to 1.8 cases per 100,000 individuals. The overall incidence was higher among African Americans, compared with whites (1.6 vs. 1.3 cases per 100,000 individuals, respectively). The incidence among African-American males was slightly higher, at 1.9 cases per 100,000 individuals.

The researchers found that nearly half of patients (48%) presented with localized disease, while 31% had regional disease. Between Periods 1 and 2 the proportion of patients who received any treatment for anal cancer increased from 63% to 74%. The use of radiation therapy increased from 61% to 72%, while the use of local excisions and abdominoperineal resections decreased from 60% to 45%. Overall, African Americans were more likely than whites to not undergo recommended surgery (9.8% vs. 8.7%, respectively) or to refuse recommended surgery (1.8% vs. 1.1%; P less than .05 for both associations).

Overall 5-year survival for anal cancer improved from 63% in Period 1 to 70% in Period 2 (P less than .05). However, African Americans had significantly lower 5-year survival rates, compared with whites in both time periods (53% vs. 64% in Period 1, and 62% vs. 71% in Period 2; P less than .05 for both associations).

“Health disparities exist in anal cancer with African Americans faring worse than Caucasian patients,” said Dr. Chu, who is a gastrointestinal surgeon at the University of Alabama at Birmingham. “While the etiologies for these disparities are unclear, anal cancer is a very treatable disease when caught early, regardless of race. Screening should be done for those at higher risk, such as patients with a family history of anal cancer, HIV, or HPV [human papillomavirus]. Ultimately, more research is needed to understand the factors driving these disparities at the patient, provider, and health care system level.”

He acknowledged certain limitations of the study, including its retrospective nature, the inability to assess the potential impact of education status and other social factors, and the generalizability of its findings, since SEER is limited to major cancer hospitals.

The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

CHICAGO – A novel plasma microRNA assay and prediction model appears to successfully differentiate colorectal neoplasia from other neoplasms and from controls.

The assay includes seven microRNAs that were selected, based on P value, area under the curve (AUC), fold change, and biological plausibility, from among 380 microRNAs screened using microfluidic array technology from a “training” cohort of 60 patients. The training cohort included groups of patients, 10 each, with colorectal cancer, advanced adenoma, breast cancer, pancreatic cancer, and lung cancer – cancers chosen because they frequently develop at similar ages as colon cancer – and 10 controls.

Dr. Carter

A panel of seven “uniquely dysregulated” microRNAs specific for colorectal neoplasia was evaluated using single assays in a “test” cohort of 120 patients. A mathematical model was developed to predict sample identity in a 150-patient blinded “validation” cohort using repeat-subsampling validation of the testing dataset with 1,000 iterations each to assess model detection accuracy, Dr. Jane V. Carter of the University of Louisville (Ky.) explained at the annual meeting of the American Surgical Association.

The area under the curve for test cohort comparisons with the assay was 0.91, 0.79, and 0.98 for comparison No. 1 (comparing any neoplasia vs. controls), comparison No. 2 (comparing colorectal neoplasia with other cancers) and comparison No. 3 (comparing colorectal cancer with colorectal adenomas) respectively, Dr. Carter reported.

“Our prediction model identified blinded sample identity with 69%-77% accuracy in comparison No. 1, 66%-76% accuracy in comparison No. 2, and 86%-90% accuracy in comparison No. 3,” she said, noting that the sensitivity and specificity of the assay compare very well with current clinical standards.

©Gio_tto/Thinkstock.com

Colorectal neoplasms frequently develop in individuals at ages when other common cancers also occur. Current screening methods, including endoscopic and imaging studies and fecal testing have poor patient compliance. Fecal and blood tests lack sensitivity and specificity for the detection of adenomas, limiting their use as screening methods, she said.

But this novel assay, which builds on the earlier work identifying miR-21 as a potential marker for colorectal cancer, provides a useful tool for identifying colorectal neoplasms, she said.

Efforts are underway to confirm the findings in a larger study population. If the findings are confirmed, the assay may have other potential uses such as monitoring therapy by comparing microRNA expression before and after treatment, and also for predicting response to treatment such as following preoperative neoadjuvant chemoradiation, Dr. Carter suggested.

The current findings have significant implications for the development of a noninvasive, reliable, and reproducible screening test for detection of colorectal neoplasia.

“If we can improve early-stage detection, we can improve survival,” she said.

Dr. Carter reported having no relevant disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

CHICAGO – A novel plasma microRNA assay and prediction model appears to successfully differentiate colorectal neoplasia from other neoplasms and from controls.

The assay includes seven microRNAs that were selected, based on P value, area under the curve (AUC), fold change, and biological plausibility, from among 380 microRNAs screened using microfluidic array technology from a “training” cohort of 60 patients. The training cohort included groups of patients, 10 each, with colorectal cancer, advanced adenoma, breast cancer, pancreatic cancer, and lung cancer – cancers chosen because they frequently develop at similar ages as colon cancer – and 10 controls.

Dr. Carter

A panel of seven “uniquely dysregulated” microRNAs specific for colorectal neoplasia was evaluated using single assays in a “test” cohort of 120 patients. A mathematical model was developed to predict sample identity in a 150-patient blinded “validation” cohort using repeat-subsampling validation of the testing dataset with 1,000 iterations each to assess model detection accuracy, Dr. Jane V. Carter of the University of Louisville (Ky.) explained at the annual meeting of the American Surgical Association.

The area under the curve for test cohort comparisons with the assay was 0.91, 0.79, and 0.98 for comparison No. 1 (comparing any neoplasia vs. controls), comparison No. 2 (comparing colorectal neoplasia with other cancers) and comparison No. 3 (comparing colorectal cancer with colorectal adenomas) respectively, Dr. Carter reported.

“Our prediction model identified blinded sample identity with 69%-77% accuracy in comparison No. 1, 66%-76% accuracy in comparison No. 2, and 86%-90% accuracy in comparison No. 3,” she said, noting that the sensitivity and specificity of the assay compare very well with current clinical standards.

©Gio_tto/Thinkstock.com

Colorectal neoplasms frequently develop in individuals at ages when other common cancers also occur. Current screening methods, including endoscopic and imaging studies and fecal testing have poor patient compliance. Fecal and blood tests lack sensitivity and specificity for the detection of adenomas, limiting their use as screening methods, she said.

But this novel assay, which builds on the earlier work identifying miR-21 as a potential marker for colorectal cancer, provides a useful tool for identifying colorectal neoplasms, she said.

Efforts are underway to confirm the findings in a larger study population. If the findings are confirmed, the assay may have other potential uses such as monitoring therapy by comparing microRNA expression before and after treatment, and also for predicting response to treatment such as following preoperative neoadjuvant chemoradiation, Dr. Carter suggested.

The current findings have significant implications for the development of a noninvasive, reliable, and reproducible screening test for detection of colorectal neoplasia.

“If we can improve early-stage detection, we can improve survival,” she said.

Dr. Carter reported having no relevant disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

CHICAGO – A novel plasma microRNA assay and prediction model appears to successfully differentiate colorectal neoplasia from other neoplasms and from controls.

The assay includes seven microRNAs that were selected, based on P value, area under the curve (AUC), fold change, and biological plausibility, from among 380 microRNAs screened using microfluidic array technology from a “training” cohort of 60 patients. The training cohort included groups of patients, 10 each, with colorectal cancer, advanced adenoma, breast cancer, pancreatic cancer, and lung cancer – cancers chosen because they frequently develop at similar ages as colon cancer – and 10 controls.

Dr. Carter

A panel of seven “uniquely dysregulated” microRNAs specific for colorectal neoplasia was evaluated using single assays in a “test” cohort of 120 patients. A mathematical model was developed to predict sample identity in a 150-patient blinded “validation” cohort using repeat-subsampling validation of the testing dataset with 1,000 iterations each to assess model detection accuracy, Dr. Jane V. Carter of the University of Louisville (Ky.) explained at the annual meeting of the American Surgical Association.

The area under the curve for test cohort comparisons with the assay was 0.91, 0.79, and 0.98 for comparison No. 1 (comparing any neoplasia vs. controls), comparison No. 2 (comparing colorectal neoplasia with other cancers) and comparison No. 3 (comparing colorectal cancer with colorectal adenomas) respectively, Dr. Carter reported.

“Our prediction model identified blinded sample identity with 69%-77% accuracy in comparison No. 1, 66%-76% accuracy in comparison No. 2, and 86%-90% accuracy in comparison No. 3,” she said, noting that the sensitivity and specificity of the assay compare very well with current clinical standards.

©Gio_tto/Thinkstock.com

Colorectal neoplasms frequently develop in individuals at ages when other common cancers also occur. Current screening methods, including endoscopic and imaging studies and fecal testing have poor patient compliance. Fecal and blood tests lack sensitivity and specificity for the detection of adenomas, limiting their use as screening methods, she said.

But this novel assay, which builds on the earlier work identifying miR-21 as a potential marker for colorectal cancer, provides a useful tool for identifying colorectal neoplasms, she said.

Efforts are underway to confirm the findings in a larger study population. If the findings are confirmed, the assay may have other potential uses such as monitoring therapy by comparing microRNA expression before and after treatment, and also for predicting response to treatment such as following preoperative neoadjuvant chemoradiation, Dr. Carter suggested.

The current findings have significant implications for the development of a noninvasive, reliable, and reproducible screening test for detection of colorectal neoplasia.

“If we can improve early-stage detection, we can improve survival,” she said.

Dr. Carter reported having no relevant disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

More reason, if any is needed, to encourage patients to kick the habit comes from a study showing an association between cigarette smoking and tumor DNA methylation changes.

In a study of tumor tissue from men with prostate cancer (PCa) who underwent radical prostatectomy, smoking was associated with differential methylation across 40 genetic regions, and at least 10 of the regions significantly correlated with levels of messenger RNA (mRNA) expression in corresponding genes.

Brett Mulcahy/ThinkStock

Men whose tumors had the highest levels of smoking-associated methylation were more likely to have higher Gleason grade tumors or regional vs. local stage disease, reported Dr. Irene M. Shui of the Fred Hutchinson Cancer Research Center in Seattle and her colleagues.

“[O]ur results provide support for the hypothesis that smoking-induced changes in DNA methylation may underlie the association of smoking with PCa recurrence and mortality,” they wrote (Cancer 2016 May 3. doi: 10.1002/cncr.30045).

To see whether DNA methylation could at least partly explain the association of smoking with increased PCa progression and mortality, the investigators looked at tumor methylation and long-term follow-up data on 523 patients, 469 of whom (90%) had matched tumor gene expression data available. In all, 43% of the men were never smokers, 47% were former smokers, and 10% were current smokers.

The investigators examined tumor methylation profiles by smoking status, with the goals of determining whether smoking-associated changes in methylation are linked to mRNA expression, and whether they are related to disease prognosis.

They found that 40 DNA methylation regions were associated with smoking, and that 10 of the regions were strongly correlated with mRNA expression. They then used these 10 regions to create a smoking-related methylation score.

As noted before, the score was associated with adverse outcomes, with men in the highest third having an odds ratio (OR) for disease recurrence of 2.29 (P = .0007), and an OR of 4.21 for death from prostate cancer (P = .004)

The associations between smoking-related methylation scores and worse outcomes were slightly less strong but still significant after adjustment for Gleason score and pathologic stage.

“Importantly, there is evidence that smoking-related methylation changes in blood may be reversible; men who quit smoking for longer periods of time have methylation profiles similar to those of never-smokers,” the authors wrote.

More reason, if any is needed, to encourage patients to kick the habit comes from a study showing an association between cigarette smoking and tumor DNA methylation changes.

In a study of tumor tissue from men with prostate cancer (PCa) who underwent radical prostatectomy, smoking was associated with differential methylation across 40 genetic regions, and at least 10 of the regions significantly correlated with levels of messenger RNA (mRNA) expression in corresponding genes.

Brett Mulcahy/ThinkStock

Men whose tumors had the highest levels of smoking-associated methylation were more likely to have higher Gleason grade tumors or regional vs. local stage disease, reported Dr. Irene M. Shui of the Fred Hutchinson Cancer Research Center in Seattle and her colleagues.

“[O]ur results provide support for the hypothesis that smoking-induced changes in DNA methylation may underlie the association of smoking with PCa recurrence and mortality,” they wrote (Cancer 2016 May 3. doi: 10.1002/cncr.30045).

To see whether DNA methylation could at least partly explain the association of smoking with increased PCa progression and mortality, the investigators looked at tumor methylation and long-term follow-up data on 523 patients, 469 of whom (90%) had matched tumor gene expression data available. In all, 43% of the men were never smokers, 47% were former smokers, and 10% were current smokers.

The investigators examined tumor methylation profiles by smoking status, with the goals of determining whether smoking-associated changes in methylation are linked to mRNA expression, and whether they are related to disease prognosis.

They found that 40 DNA methylation regions were associated with smoking, and that 10 of the regions were strongly correlated with mRNA expression. They then used these 10 regions to create a smoking-related methylation score.

As noted before, the score was associated with adverse outcomes, with men in the highest third having an odds ratio (OR) for disease recurrence of 2.29 (P = .0007), and an OR of 4.21 for death from prostate cancer (P = .004)

The associations between smoking-related methylation scores and worse outcomes were slightly less strong but still significant after adjustment for Gleason score and pathologic stage.

“Importantly, there is evidence that smoking-related methylation changes in blood may be reversible; men who quit smoking for longer periods of time have methylation profiles similar to those of never-smokers,” the authors wrote.

More reason, if any is needed, to encourage patients to kick the habit comes from a study showing an association between cigarette smoking and tumor DNA methylation changes.

In a study of tumor tissue from men with prostate cancer (PCa) who underwent radical prostatectomy, smoking was associated with differential methylation across 40 genetic regions, and at least 10 of the regions significantly correlated with levels of messenger RNA (mRNA) expression in corresponding genes.

Brett Mulcahy/ThinkStock

Men whose tumors had the highest levels of smoking-associated methylation were more likely to have higher Gleason grade tumors or regional vs. local stage disease, reported Dr. Irene M. Shui of the Fred Hutchinson Cancer Research Center in Seattle and her colleagues.

“[O]ur results provide support for the hypothesis that smoking-induced changes in DNA methylation may underlie the association of smoking with PCa recurrence and mortality,” they wrote (Cancer 2016 May 3. doi: 10.1002/cncr.30045).

To see whether DNA methylation could at least partly explain the association of smoking with increased PCa progression and mortality, the investigators looked at tumor methylation and long-term follow-up data on 523 patients, 469 of whom (90%) had matched tumor gene expression data available. In all, 43% of the men were never smokers, 47% were former smokers, and 10% were current smokers.

The investigators examined tumor methylation profiles by smoking status, with the goals of determining whether smoking-associated changes in methylation are linked to mRNA expression, and whether they are related to disease prognosis.

They found that 40 DNA methylation regions were associated with smoking, and that 10 of the regions were strongly correlated with mRNA expression. They then used these 10 regions to create a smoking-related methylation score.

As noted before, the score was associated with adverse outcomes, with men in the highest third having an odds ratio (OR) for disease recurrence of 2.29 (P = .0007), and an OR of 4.21 for death from prostate cancer (P = .004)

The associations between smoking-related methylation scores and worse outcomes were slightly less strong but still significant after adjustment for Gleason score and pathologic stage.

“Importantly, there is evidence that smoking-related methylation changes in blood may be reversible; men who quit smoking for longer periods of time have methylation profiles similar to those of never-smokers,” the authors wrote.