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VIDEO: Weight cycling common following weight loss in obese individuals
BOSTON – Examination of weight-loss patterns in over 177,000 people has revealed that, regardless of the initial 6-month weight loss, after 2 years the majority of patients become “cyclers,” with periods of weight gain and loss rather than maintenance of the initial weight loss.
“One-third of American adults are obese. In 2010, the cost of obesity and obesity-related comorbidities in the United States was estimated to be $315.8 billion. Achieving and maintaining weight loss has proven to be difficult,” said Joanna Huang, PharmD, senior manager of health economics and outcomes research at Novo Nordisk, Plainsboro, N.J., and lead investigator of the study presented at the annual meeting of the Endocrine Society.
The study examined the electronic records of about 178,000 obese patients whose weight loss had been by deliberate intent and not due to illness. The subjects were allocated into four groups based on the extent of weight loss in terms of body mass index (BMI) over 6 months: Those who remained stable and lost less than 5% (n = 151,902), those who lost 5%-10% (modest loss; n = 16,637), those who lost 10%-15% (moderate loss; n = 4,035), and those who lost in excess of 15% (high loss; n = 5,945).
The subjects who were at least 18 years of age at baseline (mean age 54-58 years), had at least one BMI measurement that was indicative of obesity (greater than or equal to 30 kg/m2), with at least four BMI determinations done over at least 5 years. Subjects were mostly white (about 66% in all four groups) and mostly from the southern United States.
Regardless of the amount that the participants lost in the first 6 months, regain of 50% of more of body weight was common in the modest weight-loss group (40%) and moderate weight-loss group (36%), while only 19% of those in the high weight-loss group cycled back up in weight, reported study presenter Maral DerSarkissian, PhD, of the Analysis Group in Boston.
More than 73% and about 70% of those in the moderate and modest weight-loss group, respectively, experienced weight cycling within 2 years. In the stable and high weight-loss groups, the situation was somewhat more optimistic, with about 60% of participants cycling in weight within 2 years. Total regain of lost weight occurred in about 23%, 16%, and 7% of the modest, moderate, and high weight-loss group, respectively.
“Weight loss maintenance, even in the moderate and high weight-loss groups, is very difficult to achieve,” said Dr. Huang.
Interventions that seek to maintain the weight conventionally are directed at dietary changes. But, according to Dr. DerSarkissian, “these modifications alone might not be enough to achieve and maintain weight loss.”
Pharmacotherapy is another weight-loss option. The data indicated that only 2% of the participants were receiving weight-loss pharmacotherapy. Whether this figure is accurate is an open question, according to Dr. Huang, since a lot of the data were compiled from physicians’ notes. Since clinicians may not record weight-loss advice offered to their patients, the data base may well not reflect lifestyle interventions, including pharmacotherapy.
In addition, since the data captured only primary outpatient care, whether or not a patient ever had bariatric surgery was unknown. Other unrecorded factors that can influence weight over time included comorbidities, use of medications, diet changes, and changes in physical activity.
The data points to a multifactor approach to weight loss that includes counseling, positive reinforcement, dietary advice, pharmacotherapy where appropriate, and, in some cases, bariatric surgery.
“Successful and sustained clinically meaningful weight loss requires chronic and effective weight management strategies,” said Dr. Huang.
Dr. Huang is an employee of Novo Nordisk and Dr. DerSarkissian is a researcher for Novo Nordisk.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Examination of weight-loss patterns in over 177,000 people has revealed that, regardless of the initial 6-month weight loss, after 2 years the majority of patients become “cyclers,” with periods of weight gain and loss rather than maintenance of the initial weight loss.
“One-third of American adults are obese. In 2010, the cost of obesity and obesity-related comorbidities in the United States was estimated to be $315.8 billion. Achieving and maintaining weight loss has proven to be difficult,” said Joanna Huang, PharmD, senior manager of health economics and outcomes research at Novo Nordisk, Plainsboro, N.J., and lead investigator of the study presented at the annual meeting of the Endocrine Society.
The study examined the electronic records of about 178,000 obese patients whose weight loss had been by deliberate intent and not due to illness. The subjects were allocated into four groups based on the extent of weight loss in terms of body mass index (BMI) over 6 months: Those who remained stable and lost less than 5% (n = 151,902), those who lost 5%-10% (modest loss; n = 16,637), those who lost 10%-15% (moderate loss; n = 4,035), and those who lost in excess of 15% (high loss; n = 5,945).
The subjects who were at least 18 years of age at baseline (mean age 54-58 years), had at least one BMI measurement that was indicative of obesity (greater than or equal to 30 kg/m2), with at least four BMI determinations done over at least 5 years. Subjects were mostly white (about 66% in all four groups) and mostly from the southern United States.
Regardless of the amount that the participants lost in the first 6 months, regain of 50% of more of body weight was common in the modest weight-loss group (40%) and moderate weight-loss group (36%), while only 19% of those in the high weight-loss group cycled back up in weight, reported study presenter Maral DerSarkissian, PhD, of the Analysis Group in Boston.
More than 73% and about 70% of those in the moderate and modest weight-loss group, respectively, experienced weight cycling within 2 years. In the stable and high weight-loss groups, the situation was somewhat more optimistic, with about 60% of participants cycling in weight within 2 years. Total regain of lost weight occurred in about 23%, 16%, and 7% of the modest, moderate, and high weight-loss group, respectively.
“Weight loss maintenance, even in the moderate and high weight-loss groups, is very difficult to achieve,” said Dr. Huang.
Interventions that seek to maintain the weight conventionally are directed at dietary changes. But, according to Dr. DerSarkissian, “these modifications alone might not be enough to achieve and maintain weight loss.”
Pharmacotherapy is another weight-loss option. The data indicated that only 2% of the participants were receiving weight-loss pharmacotherapy. Whether this figure is accurate is an open question, according to Dr. Huang, since a lot of the data were compiled from physicians’ notes. Since clinicians may not record weight-loss advice offered to their patients, the data base may well not reflect lifestyle interventions, including pharmacotherapy.
In addition, since the data captured only primary outpatient care, whether or not a patient ever had bariatric surgery was unknown. Other unrecorded factors that can influence weight over time included comorbidities, use of medications, diet changes, and changes in physical activity.
The data points to a multifactor approach to weight loss that includes counseling, positive reinforcement, dietary advice, pharmacotherapy where appropriate, and, in some cases, bariatric surgery.
“Successful and sustained clinically meaningful weight loss requires chronic and effective weight management strategies,” said Dr. Huang.
Dr. Huang is an employee of Novo Nordisk and Dr. DerSarkissian is a researcher for Novo Nordisk.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Examination of weight-loss patterns in over 177,000 people has revealed that, regardless of the initial 6-month weight loss, after 2 years the majority of patients become “cyclers,” with periods of weight gain and loss rather than maintenance of the initial weight loss.
“One-third of American adults are obese. In 2010, the cost of obesity and obesity-related comorbidities in the United States was estimated to be $315.8 billion. Achieving and maintaining weight loss has proven to be difficult,” said Joanna Huang, PharmD, senior manager of health economics and outcomes research at Novo Nordisk, Plainsboro, N.J., and lead investigator of the study presented at the annual meeting of the Endocrine Society.
The study examined the electronic records of about 178,000 obese patients whose weight loss had been by deliberate intent and not due to illness. The subjects were allocated into four groups based on the extent of weight loss in terms of body mass index (BMI) over 6 months: Those who remained stable and lost less than 5% (n = 151,902), those who lost 5%-10% (modest loss; n = 16,637), those who lost 10%-15% (moderate loss; n = 4,035), and those who lost in excess of 15% (high loss; n = 5,945).
The subjects who were at least 18 years of age at baseline (mean age 54-58 years), had at least one BMI measurement that was indicative of obesity (greater than or equal to 30 kg/m2), with at least four BMI determinations done over at least 5 years. Subjects were mostly white (about 66% in all four groups) and mostly from the southern United States.
Regardless of the amount that the participants lost in the first 6 months, regain of 50% of more of body weight was common in the modest weight-loss group (40%) and moderate weight-loss group (36%), while only 19% of those in the high weight-loss group cycled back up in weight, reported study presenter Maral DerSarkissian, PhD, of the Analysis Group in Boston.
More than 73% and about 70% of those in the moderate and modest weight-loss group, respectively, experienced weight cycling within 2 years. In the stable and high weight-loss groups, the situation was somewhat more optimistic, with about 60% of participants cycling in weight within 2 years. Total regain of lost weight occurred in about 23%, 16%, and 7% of the modest, moderate, and high weight-loss group, respectively.
“Weight loss maintenance, even in the moderate and high weight-loss groups, is very difficult to achieve,” said Dr. Huang.
Interventions that seek to maintain the weight conventionally are directed at dietary changes. But, according to Dr. DerSarkissian, “these modifications alone might not be enough to achieve and maintain weight loss.”
Pharmacotherapy is another weight-loss option. The data indicated that only 2% of the participants were receiving weight-loss pharmacotherapy. Whether this figure is accurate is an open question, according to Dr. Huang, since a lot of the data were compiled from physicians’ notes. Since clinicians may not record weight-loss advice offered to their patients, the data base may well not reflect lifestyle interventions, including pharmacotherapy.
In addition, since the data captured only primary outpatient care, whether or not a patient ever had bariatric surgery was unknown. Other unrecorded factors that can influence weight over time included comorbidities, use of medications, diet changes, and changes in physical activity.
The data points to a multifactor approach to weight loss that includes counseling, positive reinforcement, dietary advice, pharmacotherapy where appropriate, and, in some cases, bariatric surgery.
“Successful and sustained clinically meaningful weight loss requires chronic and effective weight management strategies,” said Dr. Huang.
Dr. Huang is an employee of Novo Nordisk and Dr. DerSarkissian is a researcher for Novo Nordisk.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ENDO 2016
Key clinical point: Most patients who lose modest or moderate amounts of weight experience periods of both gain and loss within 2 years.
Major finding: More than 73% and about 70% of those in the moderate and modest weight-loss group, respectively, experienced weight cycling within 2 years. Total regain of lost weight occurred in about 23%, 16%, and 7% of the modest, moderate, and high weight-loss group, respectively.
Data source: Electronic records of 177,743 obese patients whose weight loss had been by deliberate intent and not due to illness.
Disclosures: Dr. Huang is an employee of Novo Nordisk and Dr. DerSarkissian is a researcher for Novo Nordisk.
VIDEO: Childhood obesity predicted by infant BMI
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ENDO 2016
VIDEO: HOPE-3 bolsters primary prevention in intermediate-risk patients
CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.
In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.
In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.
Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.
In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.
In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.
Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.
In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.
In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.
Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ACC 16
Thyroid function and diabetes: Exploring the link
Stem cells show heart failure benefits in phase II trial
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
AT ACC 16
Key clinical point: Severe, ischemic heart failure patients had a significant cut in death and cardiovascular hospitalizations 1 year after endovascular myocardial injection with selectively expanded autologous bone marrow cells in a fully blinded, placebo-controlled phase II study.
Major finding: Cell-treated patients had a 37% drop in death and cardiovascular hospitalization relative to controls in 1-year follow-up.
Data source: A multicenter, fully blinded study with 109 patients for the per protocol efficacy analysis, and 114 patients for the safety analysis.
Disclosures: The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
VIDEO: More routine use of unilateral thyroidectomy advocated for papillary thyroid microcarcinoma
BOSTON – A study of over 60 years of patient data from the Mayo Clinic suggests a reconsideration of the routine use of unilateral thyroid lobectomy (UL) as the initial treatment for papillary thyroid microcarcinoma.
“Papillary thyroid microcarcinoma [PTM] patients have a normal life expectancy and typically are cured by adequate tumor resection. More than 99% of PTM patients are not at risk of either distant spread or mortality from cancer,” said Dr. Ian D. Hay of the Mayo Clinic, Rochester, Minn. Unilateral thyroid lobectomy is one treatment option for papillary thyroid microcarcinoma along with conventional bilateral nodal resection approaches of near-total thyroidectomy (NT) or total thyroidectomy (TT), or selective radioactive iodine remnant ablation (RRA).
Awareness of PTM is not new; examination of thyroid glands at autopsy going back decades has revealed their presence in 6%-36% of samples. A more recent development is the use of high-resolution ultrasound-guided biopsies of papillary thyroid carcinoma (PTC) lesions as small as 3 cm. For example, at the Mayo Clinic the diagnosis of PTM was about one annually from 1935 to 1944, while from 2005 to 2014 the average was close to one per day. “At Mayo, 34% of PTCs seen since 1995 are PTMs,” Dr. Hay said at the annual meeting of the Endocrine Society.
The best initial management of PTMs is disputed, with observation favored by some, TT and RRA favored by others, and ethanol ablation having been found to be effective by institutions including the Mayo Clinic. UL has been deemphasized, despite the 2015 American Thyroid Association Guidelines recommendation of UL as the usual surgical procedure for adults with PTM.
Dr. Hay and his colleagues sought to provide some clarity to the issue by taking advantage of the institute’s database of adult (18+ years) PTM patients who were consecutively treated from 1935 to 2014. The decades of data allowed a long-term look at patient outcomes. They examined data from 1,345 patients, 954 women and 391 men with a median age at surgery of 48 years. The mean follow-up was 15.4 years, representing almost 21,000 patient years. Data on tumor recurrence and cause-specific mortality were derived from a data base of over 4,300 PTC patients representing over 66,000 patient-years of observation.
Median tumor size was 7 mm (range, 0.08-1.0 cm). Extrathyroid invasion was evident in 18 (1.3%) cases and 298 tumors (26%) were multifocal. There were 399 (30%) node-positive tumors at diagnosis and 4 (0.3%) cases featuring initial distant metastases.
The mean MACIS (metastasis, age at presentation, completeness of surgical resection, invasion [extrathyroidal], size) score was 4.25 with little variation in score over time. Almost all (96%) patients had a MACIS score of under 6. Bilateral lobar resection was done in 1,132 (95%) patients, with NT or TT comprising 80% of the cases. UL was done in only 202 (15%) cases. The use of TT skyrocketed from 3% of the cases done in the first 2 decades to 40% in the last 2 decades. Regional nodes were removed at surgery in 743 (55%) cases, either by “node picking” (23%) or compartmental dissection (32%).
Overall survival following surgery in PTM patients was similar to age- and gender-matched controls (397 deaths observed, 431 deaths expected; P = .16). Only four (0.3%) patients died of PTM. The rates of locoregional recurrence were similar for the unilateral and bilateral approaches (P = .90). In 1,148 patients with potentially curable PTM, defined as the absence of metastasis at diagnosis and no gross residual disease, the rates of tumor recurrence 10, 20, and 40 years after surgery were 6%, 7%, and 10%, respectively. In these 1,148 patients, the 30-year locoregional recurrence rates after UL alone were similar to those seen after NT or TT followed by RRA (P = .99).
UL did not result in permanent unilateral vocal cord paresis or permanent hypoparathyroidism. These adversities were more likely to develop following bilateral lobectomy.
“Since [UL] produces comparable recurrence results when compared to bilateral surgery and is not associated with either cord paresis or hypoparathyroidism, then perhaps it is overdue for institutions like Mayo to individualize our treatment policies and more often employ UL when surgery, and not observation or ultrasound-guided percutaneous ethanol ablation, is chosen to treat PTM,” said Dr. Hay.
Dr. Hay was adamant on the overuse of ultrasound in the detection of small-diameter carcinomas in the decision for bilateral surgery. “It’s embarrassing how much we are wasting resources and doing too much ultrasound too often,” he said in an interview.
Dr. Hay had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – A study of over 60 years of patient data from the Mayo Clinic suggests a reconsideration of the routine use of unilateral thyroid lobectomy (UL) as the initial treatment for papillary thyroid microcarcinoma.
“Papillary thyroid microcarcinoma [PTM] patients have a normal life expectancy and typically are cured by adequate tumor resection. More than 99% of PTM patients are not at risk of either distant spread or mortality from cancer,” said Dr. Ian D. Hay of the Mayo Clinic, Rochester, Minn. Unilateral thyroid lobectomy is one treatment option for papillary thyroid microcarcinoma along with conventional bilateral nodal resection approaches of near-total thyroidectomy (NT) or total thyroidectomy (TT), or selective radioactive iodine remnant ablation (RRA).
Awareness of PTM is not new; examination of thyroid glands at autopsy going back decades has revealed their presence in 6%-36% of samples. A more recent development is the use of high-resolution ultrasound-guided biopsies of papillary thyroid carcinoma (PTC) lesions as small as 3 cm. For example, at the Mayo Clinic the diagnosis of PTM was about one annually from 1935 to 1944, while from 2005 to 2014 the average was close to one per day. “At Mayo, 34% of PTCs seen since 1995 are PTMs,” Dr. Hay said at the annual meeting of the Endocrine Society.
The best initial management of PTMs is disputed, with observation favored by some, TT and RRA favored by others, and ethanol ablation having been found to be effective by institutions including the Mayo Clinic. UL has been deemphasized, despite the 2015 American Thyroid Association Guidelines recommendation of UL as the usual surgical procedure for adults with PTM.
Dr. Hay and his colleagues sought to provide some clarity to the issue by taking advantage of the institute’s database of adult (18+ years) PTM patients who were consecutively treated from 1935 to 2014. The decades of data allowed a long-term look at patient outcomes. They examined data from 1,345 patients, 954 women and 391 men with a median age at surgery of 48 years. The mean follow-up was 15.4 years, representing almost 21,000 patient years. Data on tumor recurrence and cause-specific mortality were derived from a data base of over 4,300 PTC patients representing over 66,000 patient-years of observation.
Median tumor size was 7 mm (range, 0.08-1.0 cm). Extrathyroid invasion was evident in 18 (1.3%) cases and 298 tumors (26%) were multifocal. There were 399 (30%) node-positive tumors at diagnosis and 4 (0.3%) cases featuring initial distant metastases.
The mean MACIS (metastasis, age at presentation, completeness of surgical resection, invasion [extrathyroidal], size) score was 4.25 with little variation in score over time. Almost all (96%) patients had a MACIS score of under 6. Bilateral lobar resection was done in 1,132 (95%) patients, with NT or TT comprising 80% of the cases. UL was done in only 202 (15%) cases. The use of TT skyrocketed from 3% of the cases done in the first 2 decades to 40% in the last 2 decades. Regional nodes were removed at surgery in 743 (55%) cases, either by “node picking” (23%) or compartmental dissection (32%).
Overall survival following surgery in PTM patients was similar to age- and gender-matched controls (397 deaths observed, 431 deaths expected; P = .16). Only four (0.3%) patients died of PTM. The rates of locoregional recurrence were similar for the unilateral and bilateral approaches (P = .90). In 1,148 patients with potentially curable PTM, defined as the absence of metastasis at diagnosis and no gross residual disease, the rates of tumor recurrence 10, 20, and 40 years after surgery were 6%, 7%, and 10%, respectively. In these 1,148 patients, the 30-year locoregional recurrence rates after UL alone were similar to those seen after NT or TT followed by RRA (P = .99).
UL did not result in permanent unilateral vocal cord paresis or permanent hypoparathyroidism. These adversities were more likely to develop following bilateral lobectomy.
“Since [UL] produces comparable recurrence results when compared to bilateral surgery and is not associated with either cord paresis or hypoparathyroidism, then perhaps it is overdue for institutions like Mayo to individualize our treatment policies and more often employ UL when surgery, and not observation or ultrasound-guided percutaneous ethanol ablation, is chosen to treat PTM,” said Dr. Hay.
Dr. Hay was adamant on the overuse of ultrasound in the detection of small-diameter carcinomas in the decision for bilateral surgery. “It’s embarrassing how much we are wasting resources and doing too much ultrasound too often,” he said in an interview.
Dr. Hay had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – A study of over 60 years of patient data from the Mayo Clinic suggests a reconsideration of the routine use of unilateral thyroid lobectomy (UL) as the initial treatment for papillary thyroid microcarcinoma.
“Papillary thyroid microcarcinoma [PTM] patients have a normal life expectancy and typically are cured by adequate tumor resection. More than 99% of PTM patients are not at risk of either distant spread or mortality from cancer,” said Dr. Ian D. Hay of the Mayo Clinic, Rochester, Minn. Unilateral thyroid lobectomy is one treatment option for papillary thyroid microcarcinoma along with conventional bilateral nodal resection approaches of near-total thyroidectomy (NT) or total thyroidectomy (TT), or selective radioactive iodine remnant ablation (RRA).
Awareness of PTM is not new; examination of thyroid glands at autopsy going back decades has revealed their presence in 6%-36% of samples. A more recent development is the use of high-resolution ultrasound-guided biopsies of papillary thyroid carcinoma (PTC) lesions as small as 3 cm. For example, at the Mayo Clinic the diagnosis of PTM was about one annually from 1935 to 1944, while from 2005 to 2014 the average was close to one per day. “At Mayo, 34% of PTCs seen since 1995 are PTMs,” Dr. Hay said at the annual meeting of the Endocrine Society.
The best initial management of PTMs is disputed, with observation favored by some, TT and RRA favored by others, and ethanol ablation having been found to be effective by institutions including the Mayo Clinic. UL has been deemphasized, despite the 2015 American Thyroid Association Guidelines recommendation of UL as the usual surgical procedure for adults with PTM.
Dr. Hay and his colleagues sought to provide some clarity to the issue by taking advantage of the institute’s database of adult (18+ years) PTM patients who were consecutively treated from 1935 to 2014. The decades of data allowed a long-term look at patient outcomes. They examined data from 1,345 patients, 954 women and 391 men with a median age at surgery of 48 years. The mean follow-up was 15.4 years, representing almost 21,000 patient years. Data on tumor recurrence and cause-specific mortality were derived from a data base of over 4,300 PTC patients representing over 66,000 patient-years of observation.
Median tumor size was 7 mm (range, 0.08-1.0 cm). Extrathyroid invasion was evident in 18 (1.3%) cases and 298 tumors (26%) were multifocal. There were 399 (30%) node-positive tumors at diagnosis and 4 (0.3%) cases featuring initial distant metastases.
The mean MACIS (metastasis, age at presentation, completeness of surgical resection, invasion [extrathyroidal], size) score was 4.25 with little variation in score over time. Almost all (96%) patients had a MACIS score of under 6. Bilateral lobar resection was done in 1,132 (95%) patients, with NT or TT comprising 80% of the cases. UL was done in only 202 (15%) cases. The use of TT skyrocketed from 3% of the cases done in the first 2 decades to 40% in the last 2 decades. Regional nodes were removed at surgery in 743 (55%) cases, either by “node picking” (23%) or compartmental dissection (32%).
Overall survival following surgery in PTM patients was similar to age- and gender-matched controls (397 deaths observed, 431 deaths expected; P = .16). Only four (0.3%) patients died of PTM. The rates of locoregional recurrence were similar for the unilateral and bilateral approaches (P = .90). In 1,148 patients with potentially curable PTM, defined as the absence of metastasis at diagnosis and no gross residual disease, the rates of tumor recurrence 10, 20, and 40 years after surgery were 6%, 7%, and 10%, respectively. In these 1,148 patients, the 30-year locoregional recurrence rates after UL alone were similar to those seen after NT or TT followed by RRA (P = .99).
UL did not result in permanent unilateral vocal cord paresis or permanent hypoparathyroidism. These adversities were more likely to develop following bilateral lobectomy.
“Since [UL] produces comparable recurrence results when compared to bilateral surgery and is not associated with either cord paresis or hypoparathyroidism, then perhaps it is overdue for institutions like Mayo to individualize our treatment policies and more often employ UL when surgery, and not observation or ultrasound-guided percutaneous ethanol ablation, is chosen to treat PTM,” said Dr. Hay.
Dr. Hay was adamant on the overuse of ultrasound in the detection of small-diameter carcinomas in the decision for bilateral surgery. “It’s embarrassing how much we are wasting resources and doing too much ultrasound too often,” he said in an interview.
Dr. Hay had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ENDO 2016
Key clinical point: Unilateral thryoidectomy should be reconsidered as a routine strategy in treatment of papillary thyroid microcarcinoma.
Major finding: Data compiled from over 80 years at a single institution indicates the value of unilateral thyroidectomy in terms of recurrence and morbidity.
Data source: Retrospective analysis of data from 1,153 adult patients.
Disclosures: Dr. Hay had no disclosures.
WATCH: Why Teaching Hospital Medicine Can Be a Rewarding Career
Two academic hospitalists talk about why they teach, what they're learning from their students, and what they see as the future of hospital medicine. Since academic HM is the new-hospitalist pipeline, hearing what they're seeing in their student and resident trainee corps is a snapshot of HM's sustainability.
Two academic hospitalists talk about why they teach, what they're learning from their students, and what they see as the future of hospital medicine. Since academic HM is the new-hospitalist pipeline, hearing what they're seeing in their student and resident trainee corps is a snapshot of HM's sustainability.
Two academic hospitalists talk about why they teach, what they're learning from their students, and what they see as the future of hospital medicine. Since academic HM is the new-hospitalist pipeline, hearing what they're seeing in their student and resident trainee corps is a snapshot of HM's sustainability.
Robot-assisted laparoscopic myomectomy
The management of symptomatic uterine fibroids in the patient desiring conservative surgical therapy can be challenging at times. The advent of robot-assisted laparoscopy has provided surgeons with an enabling tool and patients with the option for a minimally invasive approach to myomectomy.
This month’s video was produced in order to demonstrate a systematic approach to the robot-assisted laparoscopic myomectomy in patients who are candidates. The example case is removal of a 5-cm, intrauterine posterior myoma in a 39-year-old woman (G3P1021) with heavy menstrual bleeding who desires future fertility.
Key objectives of the video include:
- understanding the role of radiologic imaging as part of preoperative surgical planning
- recognizing the key robotic instruments and suture selected to perform the procedure
- discussing robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair.
Also integrated into this video is the application of the ExCITE technique—a manual cold knife tissue extraction technique utilizing an extracorporeal semi-circle “C-incision” approach—for tissue extraction. This technique was featured in an earlier installment of the video channel.1
I hope that you find this month’s video helpful to your surgical practice.
Share your thoughts on this video! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Truong M, Advincula A. Minimally invasive tissue extraction made simple: the Extracorporeal C-Incision Tissue Extraction (ExCITE) technique. OBG Manag. 2014;26(11):56.
The management of symptomatic uterine fibroids in the patient desiring conservative surgical therapy can be challenging at times. The advent of robot-assisted laparoscopy has provided surgeons with an enabling tool and patients with the option for a minimally invasive approach to myomectomy.
This month’s video was produced in order to demonstrate a systematic approach to the robot-assisted laparoscopic myomectomy in patients who are candidates. The example case is removal of a 5-cm, intrauterine posterior myoma in a 39-year-old woman (G3P1021) with heavy menstrual bleeding who desires future fertility.
Key objectives of the video include:
- understanding the role of radiologic imaging as part of preoperative surgical planning
- recognizing the key robotic instruments and suture selected to perform the procedure
- discussing robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair.
Also integrated into this video is the application of the ExCITE technique—a manual cold knife tissue extraction technique utilizing an extracorporeal semi-circle “C-incision” approach—for tissue extraction. This technique was featured in an earlier installment of the video channel.1
I hope that you find this month’s video helpful to your surgical practice.
Share your thoughts on this video! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
The management of symptomatic uterine fibroids in the patient desiring conservative surgical therapy can be challenging at times. The advent of robot-assisted laparoscopy has provided surgeons with an enabling tool and patients with the option for a minimally invasive approach to myomectomy.
This month’s video was produced in order to demonstrate a systematic approach to the robot-assisted laparoscopic myomectomy in patients who are candidates. The example case is removal of a 5-cm, intrauterine posterior myoma in a 39-year-old woman (G3P1021) with heavy menstrual bleeding who desires future fertility.
Key objectives of the video include:
- understanding the role of radiologic imaging as part of preoperative surgical planning
- recognizing the key robotic instruments and suture selected to perform the procedure
- discussing robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair.
Also integrated into this video is the application of the ExCITE technique—a manual cold knife tissue extraction technique utilizing an extracorporeal semi-circle “C-incision” approach—for tissue extraction. This technique was featured in an earlier installment of the video channel.1
I hope that you find this month’s video helpful to your surgical practice.
Share your thoughts on this video! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Truong M, Advincula A. Minimally invasive tissue extraction made simple: the Extracorporeal C-Incision Tissue Extraction (ExCITE) technique. OBG Manag. 2014;26(11):56.
- Truong M, Advincula A. Minimally invasive tissue extraction made simple: the Extracorporeal C-Incision Tissue Extraction (ExCITE) technique. OBG Manag. 2014;26(11):56.
FIRE AND ICE trial called a win for cryoablation of AF
CHICAGO – The largest-ever randomized trial of catheter ablation of atrial fibrillation has ended in a draw between radiofrequency and cryoballoon ablation in safety and efficacy – and that actually represents a win for cryoablation, a simpler and far more easily mastered procedure, Dr. Karl-Heinz Kuck said at the annual meeting of the American College of Cardiology.
“We can teach physicians how to do cryoablation much more easily. That will allow more patients with atrial fibrillation to get access to catheter ablation, which is what we really need,” according to Dr. Kuck, principal investigator in the poetically named FIRE AND ICE trial and head of cardiology at St. Georg Hospital in Hamburg (Germany).
FIRE AND ICE included 769 patients in eight European countries. The participants, all of whom had antiarrhythmic drug–refractory paroxysmal atrial fibrillation (AF), were randomized to radiofrequency ablation – the long-time standard – or to cryoablation, a newer technology. Radiofrequency ablation was guided by three-dimensional electroanatomic mapping, while cryoablation utilized fluoroscopic guidance.
The primary efficacy endpoint was the 1-year rate of clinical failure, defined as an occurrence of AF, atrial flutter, or atrial tachycardia lasting for at least 30 seconds, or repeat ablation or the use of antiarrhythmic drugs following a 90-day postprocedural blanking period. The clinical failure rate was 34.6% in the cryoballoon group and similar at 35.9% in the radiofrequency group.
Serious treatment-related adverse events occurred in 10.2% of the cryoballoon group and 12.8% of the radiofrequency group, a nonsignificant difference. No procedural deaths occurred in the study.
There were, however, several significant procedural differences. Procedure time averaged 124 minutes in the cryoablation group, nearly 20 minutes less than the 142 minutes for radiofrequency ablation. However, the 17-minute fluoroscopy time in the radiofrequency group was 5 minutes shorter than for cryoablation.
Dr. Kuck said the study underestimates the true procedural differences because FIRE AND ICE was carried out by extremely experienced operators. In routine clinical practice involving non-elite operators, it’s not unusual for radiofrequency ablation fluoroscopy times to be two or even three times longer than the 17 minutes seen in the study. Plus, FIRE AND ICE was conducted when the procedure entailed two applications of the cryoballoon. Now only one application is recommended, cutting an additional 12 minutes off the total procedure time, he added.
Radiofrequency ablation takes longer because it entails creating a series of point-to-point lesions in a circle to isolate the pulmonary veins. With cryoablation, the balloon is moved into position, inflated, and a 3-minute-freeze is administered to create a circle of necrotic tissue in a single-step procedure.
Discussant Dr. Hugh G. Calkins praised the FIRE AND ICE investigators’ use of a rigorous definition of recurrence that required as little as a 30-second episode of atrial arrhythmia.
“That’s a very high bar, so I think the results are very impressive,” said Dr. Calkins, professor of medicine and of pediatrics and director of the cardiac arrhythmia service at Johns Hopkins University, Baltimore.
He commented that “this study is a clear reminder that 90% success rates just don’t happen in this field,” despite what some practitioners have claimed.
Asked how he predicts the study results will influence the field of AF ablation, Dr. Kuck replied that he foresees much wider adoption of cryoablation and a stronger endorsement of the technology in updated guideline recommendations.
“I personally believe this will be the most important development in our field in the next several years,” he added.
The electrophysiologist noted that even though current guidelines give a class Ia recommendation to catheter ablation of paroxysmal AF that’s refractory to at least one antiarrhythmic drug, at present only 4% of such patients actually undergo the procedure.
“Having just 4% of patients with AF undergo catheter ablation cannot be what we are looking for as physicians,” Dr. Kuck said. “I believe if we want to roll out catheter ablation for AF, we need simple and safe tools. This trial elegantly shows that with a simpler device that allows single-shot isolation of the pulmonary veins, we can get the same safety and efficacy as with radiofrequency ablation. I often tell people that radiofrequency ablation of atrial fibrillation is the most challenging procedure in all cardiology. We do this procedure from the groin in a moving heart. It’s a very complex technology.”
His dream, he continued, is that cryoablation will eventually enable patients with atrial fibrillation to be managed the same way electrophysiologists treat patients with Wolff-Parkinson-White syndrome; with the first episode, the patient goes to the electrophysiology catheterization lab for an ablation procedure.
“I think there’s a great message here: The cryoballoon will move catheter ablation from a niche procedure performed in specialized centers by the few guys in the world who can do it really well out into the broader world. To do that you need a tool that is safe, simple, and can be handled by the average doctor,” Dr. Kuck said.
Discussant Dr. Anthony DeMaria commented that it would be premature at this point to start thinking about cryoablation as a first approach to new-onset AF, given the roughly 35% clinical failure rate at 1 year seen in FIRE AND ICE. That rate doubtless would have been even higher had patients been equipped with implantable loop recorders, added Dr. DeMaria, professor of medicine at the University of California, San Diego.
Dr. Kuck conceded that the high recurrence rate is one of the great unsolved limitations of catheter ablation of AF.
“We don’t know how to get the pulmonary veins permanently isolated,” he said. “We can create acute lesions, but over time what we’ve seen is recovery of tissue and then reconduction by the pulmonary veins. I believe that 20% of the 40% recurrence rate is due to reconduction from the pulmonary veins, and the rest is probably due to triggers coming from other sites.”
The FIRE AND ICE trial was funded in part by Medtronic, which markets the Arctic Front Advance cryoablation catheter used in the study. Dr. Kuck reported serving on a speakers’ bureau for Medtronic and acting as a consultant to Biosense Webster, Edwards, and St. Jude.
Simultaneous with Dr. Kuck’s presentation at ACC 16, the results of FIRE AND ICE were published online (N Engl J Med. 2016 Apr 4. doi: 10.1056/NEJMoa1602014).
CHICAGO – The largest-ever randomized trial of catheter ablation of atrial fibrillation has ended in a draw between radiofrequency and cryoballoon ablation in safety and efficacy – and that actually represents a win for cryoablation, a simpler and far more easily mastered procedure, Dr. Karl-Heinz Kuck said at the annual meeting of the American College of Cardiology.
“We can teach physicians how to do cryoablation much more easily. That will allow more patients with atrial fibrillation to get access to catheter ablation, which is what we really need,” according to Dr. Kuck, principal investigator in the poetically named FIRE AND ICE trial and head of cardiology at St. Georg Hospital in Hamburg (Germany).
FIRE AND ICE included 769 patients in eight European countries. The participants, all of whom had antiarrhythmic drug–refractory paroxysmal atrial fibrillation (AF), were randomized to radiofrequency ablation – the long-time standard – or to cryoablation, a newer technology. Radiofrequency ablation was guided by three-dimensional electroanatomic mapping, while cryoablation utilized fluoroscopic guidance.
The primary efficacy endpoint was the 1-year rate of clinical failure, defined as an occurrence of AF, atrial flutter, or atrial tachycardia lasting for at least 30 seconds, or repeat ablation or the use of antiarrhythmic drugs following a 90-day postprocedural blanking period. The clinical failure rate was 34.6% in the cryoballoon group and similar at 35.9% in the radiofrequency group.
Serious treatment-related adverse events occurred in 10.2% of the cryoballoon group and 12.8% of the radiofrequency group, a nonsignificant difference. No procedural deaths occurred in the study.
There were, however, several significant procedural differences. Procedure time averaged 124 minutes in the cryoablation group, nearly 20 minutes less than the 142 minutes for radiofrequency ablation. However, the 17-minute fluoroscopy time in the radiofrequency group was 5 minutes shorter than for cryoablation.
Dr. Kuck said the study underestimates the true procedural differences because FIRE AND ICE was carried out by extremely experienced operators. In routine clinical practice involving non-elite operators, it’s not unusual for radiofrequency ablation fluoroscopy times to be two or even three times longer than the 17 minutes seen in the study. Plus, FIRE AND ICE was conducted when the procedure entailed two applications of the cryoballoon. Now only one application is recommended, cutting an additional 12 minutes off the total procedure time, he added.
Radiofrequency ablation takes longer because it entails creating a series of point-to-point lesions in a circle to isolate the pulmonary veins. With cryoablation, the balloon is moved into position, inflated, and a 3-minute-freeze is administered to create a circle of necrotic tissue in a single-step procedure.
Discussant Dr. Hugh G. Calkins praised the FIRE AND ICE investigators’ use of a rigorous definition of recurrence that required as little as a 30-second episode of atrial arrhythmia.
“That’s a very high bar, so I think the results are very impressive,” said Dr. Calkins, professor of medicine and of pediatrics and director of the cardiac arrhythmia service at Johns Hopkins University, Baltimore.
He commented that “this study is a clear reminder that 90% success rates just don’t happen in this field,” despite what some practitioners have claimed.
Asked how he predicts the study results will influence the field of AF ablation, Dr. Kuck replied that he foresees much wider adoption of cryoablation and a stronger endorsement of the technology in updated guideline recommendations.
“I personally believe this will be the most important development in our field in the next several years,” he added.
The electrophysiologist noted that even though current guidelines give a class Ia recommendation to catheter ablation of paroxysmal AF that’s refractory to at least one antiarrhythmic drug, at present only 4% of such patients actually undergo the procedure.
“Having just 4% of patients with AF undergo catheter ablation cannot be what we are looking for as physicians,” Dr. Kuck said. “I believe if we want to roll out catheter ablation for AF, we need simple and safe tools. This trial elegantly shows that with a simpler device that allows single-shot isolation of the pulmonary veins, we can get the same safety and efficacy as with radiofrequency ablation. I often tell people that radiofrequency ablation of atrial fibrillation is the most challenging procedure in all cardiology. We do this procedure from the groin in a moving heart. It’s a very complex technology.”
His dream, he continued, is that cryoablation will eventually enable patients with atrial fibrillation to be managed the same way electrophysiologists treat patients with Wolff-Parkinson-White syndrome; with the first episode, the patient goes to the electrophysiology catheterization lab for an ablation procedure.
“I think there’s a great message here: The cryoballoon will move catheter ablation from a niche procedure performed in specialized centers by the few guys in the world who can do it really well out into the broader world. To do that you need a tool that is safe, simple, and can be handled by the average doctor,” Dr. Kuck said.
Discussant Dr. Anthony DeMaria commented that it would be premature at this point to start thinking about cryoablation as a first approach to new-onset AF, given the roughly 35% clinical failure rate at 1 year seen in FIRE AND ICE. That rate doubtless would have been even higher had patients been equipped with implantable loop recorders, added Dr. DeMaria, professor of medicine at the University of California, San Diego.
Dr. Kuck conceded that the high recurrence rate is one of the great unsolved limitations of catheter ablation of AF.
“We don’t know how to get the pulmonary veins permanently isolated,” he said. “We can create acute lesions, but over time what we’ve seen is recovery of tissue and then reconduction by the pulmonary veins. I believe that 20% of the 40% recurrence rate is due to reconduction from the pulmonary veins, and the rest is probably due to triggers coming from other sites.”
The FIRE AND ICE trial was funded in part by Medtronic, which markets the Arctic Front Advance cryoablation catheter used in the study. Dr. Kuck reported serving on a speakers’ bureau for Medtronic and acting as a consultant to Biosense Webster, Edwards, and St. Jude.
Simultaneous with Dr. Kuck’s presentation at ACC 16, the results of FIRE AND ICE were published online (N Engl J Med. 2016 Apr 4. doi: 10.1056/NEJMoa1602014).
CHICAGO – The largest-ever randomized trial of catheter ablation of atrial fibrillation has ended in a draw between radiofrequency and cryoballoon ablation in safety and efficacy – and that actually represents a win for cryoablation, a simpler and far more easily mastered procedure, Dr. Karl-Heinz Kuck said at the annual meeting of the American College of Cardiology.
“We can teach physicians how to do cryoablation much more easily. That will allow more patients with atrial fibrillation to get access to catheter ablation, which is what we really need,” according to Dr. Kuck, principal investigator in the poetically named FIRE AND ICE trial and head of cardiology at St. Georg Hospital in Hamburg (Germany).
FIRE AND ICE included 769 patients in eight European countries. The participants, all of whom had antiarrhythmic drug–refractory paroxysmal atrial fibrillation (AF), were randomized to radiofrequency ablation – the long-time standard – or to cryoablation, a newer technology. Radiofrequency ablation was guided by three-dimensional electroanatomic mapping, while cryoablation utilized fluoroscopic guidance.
The primary efficacy endpoint was the 1-year rate of clinical failure, defined as an occurrence of AF, atrial flutter, or atrial tachycardia lasting for at least 30 seconds, or repeat ablation or the use of antiarrhythmic drugs following a 90-day postprocedural blanking period. The clinical failure rate was 34.6% in the cryoballoon group and similar at 35.9% in the radiofrequency group.
Serious treatment-related adverse events occurred in 10.2% of the cryoballoon group and 12.8% of the radiofrequency group, a nonsignificant difference. No procedural deaths occurred in the study.
There were, however, several significant procedural differences. Procedure time averaged 124 minutes in the cryoablation group, nearly 20 minutes less than the 142 minutes for radiofrequency ablation. However, the 17-minute fluoroscopy time in the radiofrequency group was 5 minutes shorter than for cryoablation.
Dr. Kuck said the study underestimates the true procedural differences because FIRE AND ICE was carried out by extremely experienced operators. In routine clinical practice involving non-elite operators, it’s not unusual for radiofrequency ablation fluoroscopy times to be two or even three times longer than the 17 minutes seen in the study. Plus, FIRE AND ICE was conducted when the procedure entailed two applications of the cryoballoon. Now only one application is recommended, cutting an additional 12 minutes off the total procedure time, he added.
Radiofrequency ablation takes longer because it entails creating a series of point-to-point lesions in a circle to isolate the pulmonary veins. With cryoablation, the balloon is moved into position, inflated, and a 3-minute-freeze is administered to create a circle of necrotic tissue in a single-step procedure.
Discussant Dr. Hugh G. Calkins praised the FIRE AND ICE investigators’ use of a rigorous definition of recurrence that required as little as a 30-second episode of atrial arrhythmia.
“That’s a very high bar, so I think the results are very impressive,” said Dr. Calkins, professor of medicine and of pediatrics and director of the cardiac arrhythmia service at Johns Hopkins University, Baltimore.
He commented that “this study is a clear reminder that 90% success rates just don’t happen in this field,” despite what some practitioners have claimed.
Asked how he predicts the study results will influence the field of AF ablation, Dr. Kuck replied that he foresees much wider adoption of cryoablation and a stronger endorsement of the technology in updated guideline recommendations.
“I personally believe this will be the most important development in our field in the next several years,” he added.
The electrophysiologist noted that even though current guidelines give a class Ia recommendation to catheter ablation of paroxysmal AF that’s refractory to at least one antiarrhythmic drug, at present only 4% of such patients actually undergo the procedure.
“Having just 4% of patients with AF undergo catheter ablation cannot be what we are looking for as physicians,” Dr. Kuck said. “I believe if we want to roll out catheter ablation for AF, we need simple and safe tools. This trial elegantly shows that with a simpler device that allows single-shot isolation of the pulmonary veins, we can get the same safety and efficacy as with radiofrequency ablation. I often tell people that radiofrequency ablation of atrial fibrillation is the most challenging procedure in all cardiology. We do this procedure from the groin in a moving heart. It’s a very complex technology.”
His dream, he continued, is that cryoablation will eventually enable patients with atrial fibrillation to be managed the same way electrophysiologists treat patients with Wolff-Parkinson-White syndrome; with the first episode, the patient goes to the electrophysiology catheterization lab for an ablation procedure.
“I think there’s a great message here: The cryoballoon will move catheter ablation from a niche procedure performed in specialized centers by the few guys in the world who can do it really well out into the broader world. To do that you need a tool that is safe, simple, and can be handled by the average doctor,” Dr. Kuck said.
Discussant Dr. Anthony DeMaria commented that it would be premature at this point to start thinking about cryoablation as a first approach to new-onset AF, given the roughly 35% clinical failure rate at 1 year seen in FIRE AND ICE. That rate doubtless would have been even higher had patients been equipped with implantable loop recorders, added Dr. DeMaria, professor of medicine at the University of California, San Diego.
Dr. Kuck conceded that the high recurrence rate is one of the great unsolved limitations of catheter ablation of AF.
“We don’t know how to get the pulmonary veins permanently isolated,” he said. “We can create acute lesions, but over time what we’ve seen is recovery of tissue and then reconduction by the pulmonary veins. I believe that 20% of the 40% recurrence rate is due to reconduction from the pulmonary veins, and the rest is probably due to triggers coming from other sites.”
The FIRE AND ICE trial was funded in part by Medtronic, which markets the Arctic Front Advance cryoablation catheter used in the study. Dr. Kuck reported serving on a speakers’ bureau for Medtronic and acting as a consultant to Biosense Webster, Edwards, and St. Jude.
Simultaneous with Dr. Kuck’s presentation at ACC 16, the results of FIRE AND ICE were published online (N Engl J Med. 2016 Apr 4. doi: 10.1056/NEJMoa1602014).
AT ACC 16
Key clinical point: Cryoablation of atrial fibrillation offers significant advantages over radiofrequency ablation.
Major finding: In a rigorous randomized trial, cryoablation of atrial fibrillation had a 34.6% clinical failure rate at 1 year, similar to the 35.9% rate for radiofrequency ablation.
Data source: The FIRE AND ICE trial, which randomized 769 patients with paroxysmal atrial fibrillation in eight European countries.
Disclosures: FIRE AND ICE was funded in part by Medtronic. The presenter reported serving on a speakers’ bureau for the company.
VIDEO: How to recognize and treat nonalcoholic fatty liver disease
PHILADELPHIA – Nonalcoholic fatty liver disease is on the rise worldwide, but many clinicians are unaware of how to recognize this potentially fatal condition, in part because it can be difficult to separate from common comorbidities such as obesity and diabetes.
In an interview at the Digestive Diseases: New Advances 2016 meeting, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey, Dr. Zobair M. Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, discussed what clinicians should know in order to screen for and treat this disease.
Dr. Younossi said he is a consultant to Conatus Pharmaceuticals, Enterome Bioscience, and Gilead, and on the advisory boards of Janssen, Salix Pharmaceuticals, and Vertex Pharmaceuticals.
Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
PHILADELPHIA – Nonalcoholic fatty liver disease is on the rise worldwide, but many clinicians are unaware of how to recognize this potentially fatal condition, in part because it can be difficult to separate from common comorbidities such as obesity and diabetes.
In an interview at the Digestive Diseases: New Advances 2016 meeting, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey, Dr. Zobair M. Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, discussed what clinicians should know in order to screen for and treat this disease.
Dr. Younossi said he is a consultant to Conatus Pharmaceuticals, Enterome Bioscience, and Gilead, and on the advisory boards of Janssen, Salix Pharmaceuticals, and Vertex Pharmaceuticals.
Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
PHILADELPHIA – Nonalcoholic fatty liver disease is on the rise worldwide, but many clinicians are unaware of how to recognize this potentially fatal condition, in part because it can be difficult to separate from common comorbidities such as obesity and diabetes.
In an interview at the Digestive Diseases: New Advances 2016 meeting, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey, Dr. Zobair M. Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, discussed what clinicians should know in order to screen for and treat this disease.
Dr. Younossi said he is a consultant to Conatus Pharmaceuticals, Enterome Bioscience, and Gilead, and on the advisory boards of Janssen, Salix Pharmaceuticals, and Vertex Pharmaceuticals.
Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
AT DIGESTIVE DISEASES: NEW ADVANCES 2016
