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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
ADA: Empagliflozin and liraglutide reduce type 2 CV death
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
Confirmation CT prevents unnecessary pulmonary nodule bronchoscopy
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
Key clinical point:
Major finding: Of 116 patients, eight (6.9%) – four men, four women, average age 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellation of their procedure.
Data source: Prospective series from Johns Hopkins University.
Disclosures: Three investigators reported grants and personal fees from Veran.
Counsel women against unnecessary prophylactic mastectomies
Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.
Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).
CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.
When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.
Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.
“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.
Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.
Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.
The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.
Although CPM is not associated with improved survival, it reduces the risk of contralateral breast cancer, and the significance of this fact to some patients should not be minimized.
As we move toward an ever-more personalized, patient-centered approach to care, we must thoughtfully weigh the balance between respecting patients’ preferences and leaving them with the long-term consequences associated with an “unnecessary” operation. For many women who choose CPM, the peace of mind associated with a reduced – albeit not eliminated – likelihood of subsequent cancer justifies the additional surgery and the potential attendant complications, even if the avoided cancer might not have actually shortened their lives. Furthermore, concerns about postsurgical cosmesis and symmetry can significantly affect the self-esteem of young women with breast cancer and affect their quality of life as much as, if not more than, concerns surrounding mortality and risk reduction.
Patients should be supported to make their own value-based medical decisions, but the medical community must continue to do its part to educate patients on the negligible benefits of this procedure and help to overcome the fears and misperceptions that often drive this decision.
Oluwadamilola M. Fayanju, MD, and E. Shelley Hwang, MD, are at Duke University in Durham, N.C. Their comments are adapted from an editorial (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4750). They reported having no conflicts of interest.
Although CPM is not associated with improved survival, it reduces the risk of contralateral breast cancer, and the significance of this fact to some patients should not be minimized.
As we move toward an ever-more personalized, patient-centered approach to care, we must thoughtfully weigh the balance between respecting patients’ preferences and leaving them with the long-term consequences associated with an “unnecessary” operation. For many women who choose CPM, the peace of mind associated with a reduced – albeit not eliminated – likelihood of subsequent cancer justifies the additional surgery and the potential attendant complications, even if the avoided cancer might not have actually shortened their lives. Furthermore, concerns about postsurgical cosmesis and symmetry can significantly affect the self-esteem of young women with breast cancer and affect their quality of life as much as, if not more than, concerns surrounding mortality and risk reduction.
Patients should be supported to make their own value-based medical decisions, but the medical community must continue to do its part to educate patients on the negligible benefits of this procedure and help to overcome the fears and misperceptions that often drive this decision.
Oluwadamilola M. Fayanju, MD, and E. Shelley Hwang, MD, are at Duke University in Durham, N.C. Their comments are adapted from an editorial (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4750). They reported having no conflicts of interest.
Although CPM is not associated with improved survival, it reduces the risk of contralateral breast cancer, and the significance of this fact to some patients should not be minimized.
As we move toward an ever-more personalized, patient-centered approach to care, we must thoughtfully weigh the balance between respecting patients’ preferences and leaving them with the long-term consequences associated with an “unnecessary” operation. For many women who choose CPM, the peace of mind associated with a reduced – albeit not eliminated – likelihood of subsequent cancer justifies the additional surgery and the potential attendant complications, even if the avoided cancer might not have actually shortened their lives. Furthermore, concerns about postsurgical cosmesis and symmetry can significantly affect the self-esteem of young women with breast cancer and affect their quality of life as much as, if not more than, concerns surrounding mortality and risk reduction.
Patients should be supported to make their own value-based medical decisions, but the medical community must continue to do its part to educate patients on the negligible benefits of this procedure and help to overcome the fears and misperceptions that often drive this decision.
Oluwadamilola M. Fayanju, MD, and E. Shelley Hwang, MD, are at Duke University in Durham, N.C. Their comments are adapted from an editorial (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4750). They reported having no conflicts of interest.
Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.
Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).
CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.
When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.
Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.
“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.
Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.
Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.
The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.
Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.
Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).
CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.
When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.
Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.
“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.
Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.
Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.
The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.
FROM JAMA SURGERY
Key clinical point:
Major finding: Overall, about 44% of women in the survey considered CPM, but just 38% of them knew that it did not improve survival.
Data source: Survey of 2,402 women with unilateral stage 0-II breast cancer.
Disclosures: The National Institutes of Health supported the study. One investigator reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.
50 years in pediatrics: ‘You have to get involved’
A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.
It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.
Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.
To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.
Dr. Sia has been president of the Hawaii Medical Association; president of the Hawaii chapter of the American Academy of Pediatrics; chief of staff at the Kauikeolani Children’s Hospital, Honolulu (now the Kapi‘olani Medical Center for Women and Children); chair of the American Medical Association Pediatric Delegation; and founder of the AMA’s Section Council on Pediatrics.
Positions like these eventually led him to contacts with legislators willing to listen and fund child abuse prevention, immunization programs, and other initiatives to help children. It often meant lobbying politicians for money.
“It doesn’t occur overnight; it takes chance and dedication,” said Dr. Sia, whose name, as one of its earliest champions, is now nearly synonymous with the concept of the medical home – an ideal of cradling children in a physician, family, and social services safety net of coordinated care.
Dr. Sia’s career spanned all of the developments that Pediatric News has covered over its 50 years, including the increasing recognition of autism, the earlier survival of premature infants, and phenylketonuria and other screenings at birth. He remembers all of them, and took action on many at the state and federal level.
Taking a step took courage, even when he wasn’t quite sure what to do. “I recognized autism back in the 60s. Children looked normal, were born normal, but then had trouble. I didn’t know what to do with them. That’s how I got involved with learning disabilities. I didn’t know anything, but I got involved,” he said.
With the advice of Robert Cooke, MD, another mentor and an eventual founder of the Head Start program, Dr. Sia cofounded Honolulu’s Variety School for Learning Disabilities in 1967. It’s still in operation; Don Ho and other local “variety hour” entertainers helped with early fundraising.
Dr. Sia also helped launch Healthy Start, one of the nation’s first home visit programs for at-risk kids, and an amendment to the federal Education of the Handicapped Act to extend aid to children with family and developmental challenges.
He convinced Sen. Daniel Inouye, another personal friend, to introduce the Emergency Medical Services for Children Act in the 1980s, which funded states to develop emergency medical services for children. “It was really important because kids need special instruments, IVs, and medications. I had to lobby. It was under Reaganomics,” Dr. Sia said.
At 89 years of age and recovering from a recent heart attack and open heart bypass, he is still trying to help children. Dr. Sia, who was born in Beijing, has been promoting the medical home concept in Asia. Meanwhile, he said he is worried about the fragmentation of health care in the United States, and the likely cutback in federal and state spending on kids.
Even so, “I believe in the future. I see in the generation coming up much more awareness of the whole child. I think they are going to do a much better job than I did,” but they need to learn “how to work the system.” Young physicians also must be mentored to believe in themselves, and take up the torch, he said.
A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.
It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.
Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.
To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.
Dr. Sia has been president of the Hawaii Medical Association; president of the Hawaii chapter of the American Academy of Pediatrics; chief of staff at the Kauikeolani Children’s Hospital, Honolulu (now the Kapi‘olani Medical Center for Women and Children); chair of the American Medical Association Pediatric Delegation; and founder of the AMA’s Section Council on Pediatrics.
Positions like these eventually led him to contacts with legislators willing to listen and fund child abuse prevention, immunization programs, and other initiatives to help children. It often meant lobbying politicians for money.
“It doesn’t occur overnight; it takes chance and dedication,” said Dr. Sia, whose name, as one of its earliest champions, is now nearly synonymous with the concept of the medical home – an ideal of cradling children in a physician, family, and social services safety net of coordinated care.
Dr. Sia’s career spanned all of the developments that Pediatric News has covered over its 50 years, including the increasing recognition of autism, the earlier survival of premature infants, and phenylketonuria and other screenings at birth. He remembers all of them, and took action on many at the state and federal level.
Taking a step took courage, even when he wasn’t quite sure what to do. “I recognized autism back in the 60s. Children looked normal, were born normal, but then had trouble. I didn’t know what to do with them. That’s how I got involved with learning disabilities. I didn’t know anything, but I got involved,” he said.
With the advice of Robert Cooke, MD, another mentor and an eventual founder of the Head Start program, Dr. Sia cofounded Honolulu’s Variety School for Learning Disabilities in 1967. It’s still in operation; Don Ho and other local “variety hour” entertainers helped with early fundraising.
Dr. Sia also helped launch Healthy Start, one of the nation’s first home visit programs for at-risk kids, and an amendment to the federal Education of the Handicapped Act to extend aid to children with family and developmental challenges.
He convinced Sen. Daniel Inouye, another personal friend, to introduce the Emergency Medical Services for Children Act in the 1980s, which funded states to develop emergency medical services for children. “It was really important because kids need special instruments, IVs, and medications. I had to lobby. It was under Reaganomics,” Dr. Sia said.
At 89 years of age and recovering from a recent heart attack and open heart bypass, he is still trying to help children. Dr. Sia, who was born in Beijing, has been promoting the medical home concept in Asia. Meanwhile, he said he is worried about the fragmentation of health care in the United States, and the likely cutback in federal and state spending on kids.
Even so, “I believe in the future. I see in the generation coming up much more awareness of the whole child. I think they are going to do a much better job than I did,” but they need to learn “how to work the system.” Young physicians also must be mentored to believe in themselves, and take up the torch, he said.
A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.
It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.
Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.
To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.
Dr. Sia has been president of the Hawaii Medical Association; president of the Hawaii chapter of the American Academy of Pediatrics; chief of staff at the Kauikeolani Children’s Hospital, Honolulu (now the Kapi‘olani Medical Center for Women and Children); chair of the American Medical Association Pediatric Delegation; and founder of the AMA’s Section Council on Pediatrics.
Positions like these eventually led him to contacts with legislators willing to listen and fund child abuse prevention, immunization programs, and other initiatives to help children. It often meant lobbying politicians for money.
“It doesn’t occur overnight; it takes chance and dedication,” said Dr. Sia, whose name, as one of its earliest champions, is now nearly synonymous with the concept of the medical home – an ideal of cradling children in a physician, family, and social services safety net of coordinated care.
Dr. Sia’s career spanned all of the developments that Pediatric News has covered over its 50 years, including the increasing recognition of autism, the earlier survival of premature infants, and phenylketonuria and other screenings at birth. He remembers all of them, and took action on many at the state and federal level.
Taking a step took courage, even when he wasn’t quite sure what to do. “I recognized autism back in the 60s. Children looked normal, were born normal, but then had trouble. I didn’t know what to do with them. That’s how I got involved with learning disabilities. I didn’t know anything, but I got involved,” he said.
With the advice of Robert Cooke, MD, another mentor and an eventual founder of the Head Start program, Dr. Sia cofounded Honolulu’s Variety School for Learning Disabilities in 1967. It’s still in operation; Don Ho and other local “variety hour” entertainers helped with early fundraising.
Dr. Sia also helped launch Healthy Start, one of the nation’s first home visit programs for at-risk kids, and an amendment to the federal Education of the Handicapped Act to extend aid to children with family and developmental challenges.
He convinced Sen. Daniel Inouye, another personal friend, to introduce the Emergency Medical Services for Children Act in the 1980s, which funded states to develop emergency medical services for children. “It was really important because kids need special instruments, IVs, and medications. I had to lobby. It was under Reaganomics,” Dr. Sia said.
At 89 years of age and recovering from a recent heart attack and open heart bypass, he is still trying to help children. Dr. Sia, who was born in Beijing, has been promoting the medical home concept in Asia. Meanwhile, he said he is worried about the fragmentation of health care in the United States, and the likely cutback in federal and state spending on kids.
Even so, “I believe in the future. I see in the generation coming up much more awareness of the whole child. I think they are going to do a much better job than I did,” but they need to learn “how to work the system.” Young physicians also must be mentored to believe in themselves, and take up the torch, he said.
FDA warning: General anesthetics may damage young brains
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
Gene therapy to boost levodopa conversion enzyme shows benefit in Parkinson’s
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Key clinical point:
Major finding: Cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months.
Data source: Phase Ib testing in 10 advanced Parkinson’s disease patients.
Disclosures: The study was funded and conducted by Voyager Therapeutics. The company announced the results; they have not been published in a peer-reviewed journal.
Risk models for hernia recurrence don’t hold up to external validation
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
FROM THE JOURNAL OF SURGICAL RESEARCH
Key clinical point:
Major finding: Risk models developed from the five strategies weren’t much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Data source: Analysis of two datasets containing a total of 2,015 ventral hernia repair patients.
Disclosures: The National Institutes of Health funded the work. Author disclosures were not reported.
Echocardiogram, exercise testing improve PAH prognostic accuracy
Adding echocardiography and cardiopulmonary exercise testing to baseline right heart catheterization improves prognostic accuracy in idiopathic pulmonary arterial hypertension, according to a prospective Italian study of 102 newly diagnosed patients.
A combination of low right ventricular fractional area change (RVFAC) on echocardiography and low oxygen pulse on cardiopulmonary exercise testing (CPET) “identifies patients at a particularly high risk of clinical deterioration.” Both are markers of right ventricular (RV) function, which is a major determinant of outcome in idiopathic pulmonary arterial hypertension [iPAH], said investigators led by Roberto Badagliacca, MD, of the Sapienza University of Rome (Chest. 2016 Aug 20. pii: S0012-3692(16)56052-8. doi: 10.1016/j.chest.2016.07.036).
PAH diagnosis requires right heart catheterization, and findings have long been known to predict PAH outcome. However, catheterization allows only “an indirect description of RV function,” the investigators said. Recent studies have shown that RV echocardiography and CPET improve the accuracy of heart failure prognosis, so the investigators wanted to see if they’d do the same for PAH.
Their results “strongly suggest that noninvasive measurements related to RV function obtained by combining resting echocardiography and CPET are of added value to right heart catheterization in the assessment of severity and prognostication of PAH,” they said.
During a mean follow-up of 528 days, 54 patients (53%) had clinical worsening, defined as a 15% reduction in 6-minute walk distance from baseline plus a worsening of functional class, nonelective PAH hospitalization, or death.
Baseline functional class and cardiac index proved to be independent predictors of clinical worsening. Adding echocardiographic and CPET variables independently improved prognostic power (area under the curve, 0.81 vs. 0.66; P = .005).
Compared with patients with high RVFAC and high oxygen pulse at baseline, patients with low RVFAC and low oxygen pulse had a 99.8 increase in the hazard ratio for clinical worsening, and those with high RVFAC and low oxygen had a 29.4 increase (P = .0001).
Several echocardiographic variables for RV function have previously been reported as independent predictors of PAH outcome. “The new finding here is that RVFAC outperformed other echocardiographic indices of systolic function,” the investigators wrote.
“As for peak oxygen pulse, this variable is thought to assess maximum [stroke volume],” assumed to be determined by RV function; MRI-determined stroke volume has been previously shown to be an important predictor of survival in PAH,” they said.
The mean age in the study was 52 years, mean functional class was 2.7, and mean 6-minute walk distance was 430 m; 62 subjects were women. The most relevant comorbidities were diabetes in 5 patients, hypercholesterolemia in 10, thyroid diseases in 6, and clinical depression in 7. Patients with severe tricuspid regurgitation or exercise-induced opening of the foramen ovale were excluded. However, a reanalysis including patients with exercise-induced right to left shunting showed the same independent predictors of PAH outcome.
After diagnosis, patients were treated with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids.
Dr. Badagliacca reported speaker and adviser fees from United Therapeutics, Dompe, GSK, and Bayer. His colleagues reported no conflicts of interest.
Adding echocardiography and cardiopulmonary exercise testing to baseline right heart catheterization improves prognostic accuracy in idiopathic pulmonary arterial hypertension, according to a prospective Italian study of 102 newly diagnosed patients.
A combination of low right ventricular fractional area change (RVFAC) on echocardiography and low oxygen pulse on cardiopulmonary exercise testing (CPET) “identifies patients at a particularly high risk of clinical deterioration.” Both are markers of right ventricular (RV) function, which is a major determinant of outcome in idiopathic pulmonary arterial hypertension [iPAH], said investigators led by Roberto Badagliacca, MD, of the Sapienza University of Rome (Chest. 2016 Aug 20. pii: S0012-3692(16)56052-8. doi: 10.1016/j.chest.2016.07.036).
PAH diagnosis requires right heart catheterization, and findings have long been known to predict PAH outcome. However, catheterization allows only “an indirect description of RV function,” the investigators said. Recent studies have shown that RV echocardiography and CPET improve the accuracy of heart failure prognosis, so the investigators wanted to see if they’d do the same for PAH.
Their results “strongly suggest that noninvasive measurements related to RV function obtained by combining resting echocardiography and CPET are of added value to right heart catheterization in the assessment of severity and prognostication of PAH,” they said.
During a mean follow-up of 528 days, 54 patients (53%) had clinical worsening, defined as a 15% reduction in 6-minute walk distance from baseline plus a worsening of functional class, nonelective PAH hospitalization, or death.
Baseline functional class and cardiac index proved to be independent predictors of clinical worsening. Adding echocardiographic and CPET variables independently improved prognostic power (area under the curve, 0.81 vs. 0.66; P = .005).
Compared with patients with high RVFAC and high oxygen pulse at baseline, patients with low RVFAC and low oxygen pulse had a 99.8 increase in the hazard ratio for clinical worsening, and those with high RVFAC and low oxygen had a 29.4 increase (P = .0001).
Several echocardiographic variables for RV function have previously been reported as independent predictors of PAH outcome. “The new finding here is that RVFAC outperformed other echocardiographic indices of systolic function,” the investigators wrote.
“As for peak oxygen pulse, this variable is thought to assess maximum [stroke volume],” assumed to be determined by RV function; MRI-determined stroke volume has been previously shown to be an important predictor of survival in PAH,” they said.
The mean age in the study was 52 years, mean functional class was 2.7, and mean 6-minute walk distance was 430 m; 62 subjects were women. The most relevant comorbidities were diabetes in 5 patients, hypercholesterolemia in 10, thyroid diseases in 6, and clinical depression in 7. Patients with severe tricuspid regurgitation or exercise-induced opening of the foramen ovale were excluded. However, a reanalysis including patients with exercise-induced right to left shunting showed the same independent predictors of PAH outcome.
After diagnosis, patients were treated with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids.
Dr. Badagliacca reported speaker and adviser fees from United Therapeutics, Dompe, GSK, and Bayer. His colleagues reported no conflicts of interest.
Adding echocardiography and cardiopulmonary exercise testing to baseline right heart catheterization improves prognostic accuracy in idiopathic pulmonary arterial hypertension, according to a prospective Italian study of 102 newly diagnosed patients.
A combination of low right ventricular fractional area change (RVFAC) on echocardiography and low oxygen pulse on cardiopulmonary exercise testing (CPET) “identifies patients at a particularly high risk of clinical deterioration.” Both are markers of right ventricular (RV) function, which is a major determinant of outcome in idiopathic pulmonary arterial hypertension [iPAH], said investigators led by Roberto Badagliacca, MD, of the Sapienza University of Rome (Chest. 2016 Aug 20. pii: S0012-3692(16)56052-8. doi: 10.1016/j.chest.2016.07.036).
PAH diagnosis requires right heart catheterization, and findings have long been known to predict PAH outcome. However, catheterization allows only “an indirect description of RV function,” the investigators said. Recent studies have shown that RV echocardiography and CPET improve the accuracy of heart failure prognosis, so the investigators wanted to see if they’d do the same for PAH.
Their results “strongly suggest that noninvasive measurements related to RV function obtained by combining resting echocardiography and CPET are of added value to right heart catheterization in the assessment of severity and prognostication of PAH,” they said.
During a mean follow-up of 528 days, 54 patients (53%) had clinical worsening, defined as a 15% reduction in 6-minute walk distance from baseline plus a worsening of functional class, nonelective PAH hospitalization, or death.
Baseline functional class and cardiac index proved to be independent predictors of clinical worsening. Adding echocardiographic and CPET variables independently improved prognostic power (area under the curve, 0.81 vs. 0.66; P = .005).
Compared with patients with high RVFAC and high oxygen pulse at baseline, patients with low RVFAC and low oxygen pulse had a 99.8 increase in the hazard ratio for clinical worsening, and those with high RVFAC and low oxygen had a 29.4 increase (P = .0001).
Several echocardiographic variables for RV function have previously been reported as independent predictors of PAH outcome. “The new finding here is that RVFAC outperformed other echocardiographic indices of systolic function,” the investigators wrote.
“As for peak oxygen pulse, this variable is thought to assess maximum [stroke volume],” assumed to be determined by RV function; MRI-determined stroke volume has been previously shown to be an important predictor of survival in PAH,” they said.
The mean age in the study was 52 years, mean functional class was 2.7, and mean 6-minute walk distance was 430 m; 62 subjects were women. The most relevant comorbidities were diabetes in 5 patients, hypercholesterolemia in 10, thyroid diseases in 6, and clinical depression in 7. Patients with severe tricuspid regurgitation or exercise-induced opening of the foramen ovale were excluded. However, a reanalysis including patients with exercise-induced right to left shunting showed the same independent predictors of PAH outcome.
After diagnosis, patients were treated with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids.
Dr. Badagliacca reported speaker and adviser fees from United Therapeutics, Dompe, GSK, and Bayer. His colleagues reported no conflicts of interest.
FROM CHEST
Key clinical point:
Major finding: Baseline functional class and cardiac index proved to be independent predictors of clinical worsening. Adding echocardiographic and CPET variables independently improved prognostic power (area under the curve, 0.81 vs. 0.66; P = .005).
Data source: A prospective Italian study of 102 newly diagnosed patients.
Disclosures: The lead investigator reported speaker and adviser fees from United Therapeutics, Dompe, GSK, and Bayer.
Genetics dictate interferon-alfa diarrhea risk
Genetics are probably to blame for why some patients have significant intestinal side effects from Roferon-A (interferon alfa-2a, recombinant – Roche) while others do not, according to a new French investigation reported in issue of Cellular and Molecular Gastroenterology and Hepatology.
They cultured intestinal wall samples taken from 20 colon cancer patients when they had surgery; none of them had been exposed to chemotherapy, radiation, or immunosuppressives. The team bathed the cells in IFN-alfa 2a and other biochemicals to see how they reacted. It was bench work, but the findings could eventually be useful if the team identifies the genetic risk factors for Roferon intestinal side effects and finds better options for patients at risk. Roferon is widely used for blood cancer, melanoma, viral hepatitis, and renal and hepatocellular carcinomas.
“IFN-alfa 2a elicited a rapid (24 hours) disruption of surface and crypt colonic epithelial cells via apoptosis that was variable in intensity among the 20 individuals studied. This apoptotic effect was dependent on the initiation of an IFN-gamma response … expressed in T cell–positive lamina propria cells,” the investigators said.
“IFN-alfa impairs human intestinal mucosa homeostasis by eliciting epithelial barrier disruption via apoptosis … The IFN-alfa–elicited impairment of intestinal mucosa homeostasis is heterogeneous among individuals,” Dr. Jarry and her associates wrote.
“This ex vivo finding parallels clinical observations of the interpatient variability of Roferon therapy side effects. … It has been reported that approximately 60% of patients with chronic hepatitis or cancer treated with Roferon have intestinal disorders, especially diarrhea,” they said.
The authors had no conflicts of interest. The work was funded by the University of Nantes.
Many studies have implicated cytokines in various human GI-tract disorders, but there is still limited information in the literature about their exact role in the maintenance and disturbance of tissue homeostasis and the molecular mechanisms involved.
Interestingly, IFN-alfa did not induce apoptosis in all human colonic fragments analyzed, showing that their culture model accounts for variability among individuals, recapitulating the heterogeneous response of cancer patients to IFN-alfa-based treatment who present with intestinal dysfunction as a side effect. The use of such models of human primary cell culture helps us develop a better understanding of how cytokines affect the GI mucosa, potentially leading to alternative targets for treatments. They also could be used to determine the individual patient differences underlying diverse responses to cytokines and drugs, which is particularly important to the advance of precision/personalized medicine.
Jason C. Mills, MD, PhD, and Luciana H. Osaki, PhD, are with the division of gastroenterology, departments of medicine, pathology and immunology, and developmental biology, Washington University, St. Louis. They have no conflicts of interest.
Many studies have implicated cytokines in various human GI-tract disorders, but there is still limited information in the literature about their exact role in the maintenance and disturbance of tissue homeostasis and the molecular mechanisms involved.
Interestingly, IFN-alfa did not induce apoptosis in all human colonic fragments analyzed, showing that their culture model accounts for variability among individuals, recapitulating the heterogeneous response of cancer patients to IFN-alfa-based treatment who present with intestinal dysfunction as a side effect. The use of such models of human primary cell culture helps us develop a better understanding of how cytokines affect the GI mucosa, potentially leading to alternative targets for treatments. They also could be used to determine the individual patient differences underlying diverse responses to cytokines and drugs, which is particularly important to the advance of precision/personalized medicine.
Jason C. Mills, MD, PhD, and Luciana H. Osaki, PhD, are with the division of gastroenterology, departments of medicine, pathology and immunology, and developmental biology, Washington University, St. Louis. They have no conflicts of interest.
Many studies have implicated cytokines in various human GI-tract disorders, but there is still limited information in the literature about their exact role in the maintenance and disturbance of tissue homeostasis and the molecular mechanisms involved.
Interestingly, IFN-alfa did not induce apoptosis in all human colonic fragments analyzed, showing that their culture model accounts for variability among individuals, recapitulating the heterogeneous response of cancer patients to IFN-alfa-based treatment who present with intestinal dysfunction as a side effect. The use of such models of human primary cell culture helps us develop a better understanding of how cytokines affect the GI mucosa, potentially leading to alternative targets for treatments. They also could be used to determine the individual patient differences underlying diverse responses to cytokines and drugs, which is particularly important to the advance of precision/personalized medicine.
Jason C. Mills, MD, PhD, and Luciana H. Osaki, PhD, are with the division of gastroenterology, departments of medicine, pathology and immunology, and developmental biology, Washington University, St. Louis. They have no conflicts of interest.
Genetics are probably to blame for why some patients have significant intestinal side effects from Roferon-A (interferon alfa-2a, recombinant – Roche) while others do not, according to a new French investigation reported in issue of Cellular and Molecular Gastroenterology and Hepatology.
They cultured intestinal wall samples taken from 20 colon cancer patients when they had surgery; none of them had been exposed to chemotherapy, radiation, or immunosuppressives. The team bathed the cells in IFN-alfa 2a and other biochemicals to see how they reacted. It was bench work, but the findings could eventually be useful if the team identifies the genetic risk factors for Roferon intestinal side effects and finds better options for patients at risk. Roferon is widely used for blood cancer, melanoma, viral hepatitis, and renal and hepatocellular carcinomas.
“IFN-alfa 2a elicited a rapid (24 hours) disruption of surface and crypt colonic epithelial cells via apoptosis that was variable in intensity among the 20 individuals studied. This apoptotic effect was dependent on the initiation of an IFN-gamma response … expressed in T cell–positive lamina propria cells,” the investigators said.
“IFN-alfa impairs human intestinal mucosa homeostasis by eliciting epithelial barrier disruption via apoptosis … The IFN-alfa–elicited impairment of intestinal mucosa homeostasis is heterogeneous among individuals,” Dr. Jarry and her associates wrote.
“This ex vivo finding parallels clinical observations of the interpatient variability of Roferon therapy side effects. … It has been reported that approximately 60% of patients with chronic hepatitis or cancer treated with Roferon have intestinal disorders, especially diarrhea,” they said.
The authors had no conflicts of interest. The work was funded by the University of Nantes.
Genetics are probably to blame for why some patients have significant intestinal side effects from Roferon-A (interferon alfa-2a, recombinant – Roche) while others do not, according to a new French investigation reported in issue of Cellular and Molecular Gastroenterology and Hepatology.
They cultured intestinal wall samples taken from 20 colon cancer patients when they had surgery; none of them had been exposed to chemotherapy, radiation, or immunosuppressives. The team bathed the cells in IFN-alfa 2a and other biochemicals to see how they reacted. It was bench work, but the findings could eventually be useful if the team identifies the genetic risk factors for Roferon intestinal side effects and finds better options for patients at risk. Roferon is widely used for blood cancer, melanoma, viral hepatitis, and renal and hepatocellular carcinomas.
“IFN-alfa 2a elicited a rapid (24 hours) disruption of surface and crypt colonic epithelial cells via apoptosis that was variable in intensity among the 20 individuals studied. This apoptotic effect was dependent on the initiation of an IFN-gamma response … expressed in T cell–positive lamina propria cells,” the investigators said.
“IFN-alfa impairs human intestinal mucosa homeostasis by eliciting epithelial barrier disruption via apoptosis … The IFN-alfa–elicited impairment of intestinal mucosa homeostasis is heterogeneous among individuals,” Dr. Jarry and her associates wrote.
“This ex vivo finding parallels clinical observations of the interpatient variability of Roferon therapy side effects. … It has been reported that approximately 60% of patients with chronic hepatitis or cancer treated with Roferon have intestinal disorders, especially diarrhea,” they said.
The authors had no conflicts of interest. The work was funded by the University of Nantes.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Fecal calprotectin tops CRP as Crohn’s marker
Stool calprotectin correlates with severity of small-bowel Crohn’s disease, as measured against balloon-assisted enteroscopy and computed tomography enterography, according to a review reported in the January issue of Clinical Gastroenterology and Hepatology of 89 patients at Toho University in Chiba, Japan.
Although the correlation was moderate, the findings suggest that fecal calprotectin (FC), with additional work, might turn out to be a good biomarker for tracking small-bowel Crohn’s disease (CD) and its response to tumor necrosis factor blockers. “Currently, it is not widely accepted that FC relates to disease activity in patients with small-intestinal CD,” said investigators led by Tsunetaka Arai of Toho University’s division of gastroenterology and hepatology (Clin Gastroenterol Hepatol. 2016 Aug 23. doi: 10.1016/j.cgh.2016.08.015).
Gastroenterologists need a decent biomarker for small-bowel Crohn’s because old-school endoscopy falls short. Adhesions and strictures block endoscopes, and sometimes scopes simply can’t reach the disease site.
Balloon-assisted enteroscopy (BAE) and computed tomography enterography (CTE) have emerged in recent years as alternatives, but, even so, the need persists for a noninvasive and inexpensive biomarker that’s better than the current standard of C-reactive protein (CRP), which can be thrown off by systemic inflammation, among other problems. The Toho investigators “believe that FC could be a relevant surrogate marker of disease activity in small-bowel CD.” Stool calprotectin paralleled disease activity in their study, while “neither the CDAI [CD activity index] score nor serum CRP showed similar correlation,” they said.
However, elevations in FC – a calcium- and zinc-binding protein released when neutrophils, monocytes, and macrophages inflame the intestinal mucosa – was independent of CD location, which signals the need for further investigation.
Meanwhile, the decent correlation between FC and CTE in the study “should [also] mean that” they could be used together to reliably define mucosal healing. CTE on its own “showed good correlation” with BAE; a CTE score/segment less than 2 [was] associated with endoscopic mucosal healing” on BAE, the investigators said.
The study subjects were an average of 32 years old, and had CD for 9 years; most were men. They had highly active disease at their first endoscopy (average CDAI of 120 points), and an average CRP of 1.09 mg/dL. Twenty-seven patients (30.3%) had small-bowel CD, 50 (56.2%) had ileocolonic CD, and 12 (13.5%) had colonic CD.
They all had endoscopic exams, BAE, and FC stool testing; those with strictures (17) went on to CTE; CTE detected every lesion despite the strictures.
The authors had no conflicts of interest.
Stool calprotectin correlates with severity of small-bowel Crohn’s disease, as measured against balloon-assisted enteroscopy and computed tomography enterography, according to a review reported in the January issue of Clinical Gastroenterology and Hepatology of 89 patients at Toho University in Chiba, Japan.
Although the correlation was moderate, the findings suggest that fecal calprotectin (FC), with additional work, might turn out to be a good biomarker for tracking small-bowel Crohn’s disease (CD) and its response to tumor necrosis factor blockers. “Currently, it is not widely accepted that FC relates to disease activity in patients with small-intestinal CD,” said investigators led by Tsunetaka Arai of Toho University’s division of gastroenterology and hepatology (Clin Gastroenterol Hepatol. 2016 Aug 23. doi: 10.1016/j.cgh.2016.08.015).
Gastroenterologists need a decent biomarker for small-bowel Crohn’s because old-school endoscopy falls short. Adhesions and strictures block endoscopes, and sometimes scopes simply can’t reach the disease site.
Balloon-assisted enteroscopy (BAE) and computed tomography enterography (CTE) have emerged in recent years as alternatives, but, even so, the need persists for a noninvasive and inexpensive biomarker that’s better than the current standard of C-reactive protein (CRP), which can be thrown off by systemic inflammation, among other problems. The Toho investigators “believe that FC could be a relevant surrogate marker of disease activity in small-bowel CD.” Stool calprotectin paralleled disease activity in their study, while “neither the CDAI [CD activity index] score nor serum CRP showed similar correlation,” they said.
However, elevations in FC – a calcium- and zinc-binding protein released when neutrophils, monocytes, and macrophages inflame the intestinal mucosa – was independent of CD location, which signals the need for further investigation.
Meanwhile, the decent correlation between FC and CTE in the study “should [also] mean that” they could be used together to reliably define mucosal healing. CTE on its own “showed good correlation” with BAE; a CTE score/segment less than 2 [was] associated with endoscopic mucosal healing” on BAE, the investigators said.
The study subjects were an average of 32 years old, and had CD for 9 years; most were men. They had highly active disease at their first endoscopy (average CDAI of 120 points), and an average CRP of 1.09 mg/dL. Twenty-seven patients (30.3%) had small-bowel CD, 50 (56.2%) had ileocolonic CD, and 12 (13.5%) had colonic CD.
They all had endoscopic exams, BAE, and FC stool testing; those with strictures (17) went on to CTE; CTE detected every lesion despite the strictures.
The authors had no conflicts of interest.
Stool calprotectin correlates with severity of small-bowel Crohn’s disease, as measured against balloon-assisted enteroscopy and computed tomography enterography, according to a review reported in the January issue of Clinical Gastroenterology and Hepatology of 89 patients at Toho University in Chiba, Japan.
Although the correlation was moderate, the findings suggest that fecal calprotectin (FC), with additional work, might turn out to be a good biomarker for tracking small-bowel Crohn’s disease (CD) and its response to tumor necrosis factor blockers. “Currently, it is not widely accepted that FC relates to disease activity in patients with small-intestinal CD,” said investigators led by Tsunetaka Arai of Toho University’s division of gastroenterology and hepatology (Clin Gastroenterol Hepatol. 2016 Aug 23. doi: 10.1016/j.cgh.2016.08.015).
Gastroenterologists need a decent biomarker for small-bowel Crohn’s because old-school endoscopy falls short. Adhesions and strictures block endoscopes, and sometimes scopes simply can’t reach the disease site.
Balloon-assisted enteroscopy (BAE) and computed tomography enterography (CTE) have emerged in recent years as alternatives, but, even so, the need persists for a noninvasive and inexpensive biomarker that’s better than the current standard of C-reactive protein (CRP), which can be thrown off by systemic inflammation, among other problems. The Toho investigators “believe that FC could be a relevant surrogate marker of disease activity in small-bowel CD.” Stool calprotectin paralleled disease activity in their study, while “neither the CDAI [CD activity index] score nor serum CRP showed similar correlation,” they said.
However, elevations in FC – a calcium- and zinc-binding protein released when neutrophils, monocytes, and macrophages inflame the intestinal mucosa – was independent of CD location, which signals the need for further investigation.
Meanwhile, the decent correlation between FC and CTE in the study “should [also] mean that” they could be used together to reliably define mucosal healing. CTE on its own “showed good correlation” with BAE; a CTE score/segment less than 2 [was] associated with endoscopic mucosal healing” on BAE, the investigators said.
The study subjects were an average of 32 years old, and had CD for 9 years; most were men. They had highly active disease at their first endoscopy (average CDAI of 120 points), and an average CRP of 1.09 mg/dL. Twenty-seven patients (30.3%) had small-bowel CD, 50 (56.2%) had ileocolonic CD, and 12 (13.5%) had colonic CD.
They all had endoscopic exams, BAE, and FC stool testing; those with strictures (17) went on to CTE; CTE detected every lesion despite the strictures.
The authors had no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point:
Major finding: A fecal calprotectin cutoff of 215 mcg/g identified mucosal healing with 82.8% sensitivity, 71.4% specificity, and an AUC of 0.81.
Data source: Review of 89 Crohn’s patients
Disclosures: The investigators had no conflicts of interest.