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VIDEO: Fix physician burnout? You need more than yoga
NEW ORLEANS – Among a growing number of physicians, the words of a Righteous Brothers’ song ring true about their careers: They’ve lost that loving feeling.
For burned-out physicians, “they’ve lost that sense that they’re making a difference,” explained Susan Thompson Hingle, MD, of Southern Illinois University in Springfield. And the solutions aren’t simple. “You can’t yoga your way out of this,” Dr. Hingle cautioned.
At the annual meeting of the American College of Physicians, Dr. Hingle and Daisy Smith, MD, vice president of clinical programs at the ACP, talked about solutions to burnout, including how more traditional approaches can boost physician well-being, such as team-based care, physician champions, and increasing the pool of primary care providers.
But they also detailed ways that struggling physicians can find support from an unlikely source: their patients.
Dr. Smith’s video interview:
Dr. Hingle’s video interview:
NEW ORLEANS – Among a growing number of physicians, the words of a Righteous Brothers’ song ring true about their careers: They’ve lost that loving feeling.
For burned-out physicians, “they’ve lost that sense that they’re making a difference,” explained Susan Thompson Hingle, MD, of Southern Illinois University in Springfield. And the solutions aren’t simple. “You can’t yoga your way out of this,” Dr. Hingle cautioned.
At the annual meeting of the American College of Physicians, Dr. Hingle and Daisy Smith, MD, vice president of clinical programs at the ACP, talked about solutions to burnout, including how more traditional approaches can boost physician well-being, such as team-based care, physician champions, and increasing the pool of primary care providers.
But they also detailed ways that struggling physicians can find support from an unlikely source: their patients.
Dr. Smith’s video interview:
Dr. Hingle’s video interview:
NEW ORLEANS – Among a growing number of physicians, the words of a Righteous Brothers’ song ring true about their careers: They’ve lost that loving feeling.
For burned-out physicians, “they’ve lost that sense that they’re making a difference,” explained Susan Thompson Hingle, MD, of Southern Illinois University in Springfield. And the solutions aren’t simple. “You can’t yoga your way out of this,” Dr. Hingle cautioned.
At the annual meeting of the American College of Physicians, Dr. Hingle and Daisy Smith, MD, vice president of clinical programs at the ACP, talked about solutions to burnout, including how more traditional approaches can boost physician well-being, such as team-based care, physician champions, and increasing the pool of primary care providers.
But they also detailed ways that struggling physicians can find support from an unlikely source: their patients.
Dr. Smith’s video interview:
Dr. Hingle’s video interview:
REPORTING FROM ACP INTERNAL MEDICINE
VIDEO: A treatment plan for medicine’s gender inequities
NEW ORLEANS – Gender inequities may pervade the medical profession, but a new generation of younger physicians – women and men – can help reshape medicine’s mindsets and workplaces.
At the annual meeting of the American College of Physicians, Sue Bornstein, MD, former chief of staff at Baylor University Medical Center in Dallas, and Darilyn Moyer, MD, CEO of the American College of Physicians, talked about the challenges to closing medicine’s gender-equity gaps, from structural bias to backlash. And they outlined strategies for women to broaden career opportunities and achieve fair payment – from mentoring and sponsoring, to leading change from the top of organizations.
The ACP published a position paper on achieving gender equity in the Annals of Internal Medicine.
Dr. Bornstein’s interview:
Dr. Moyer’s interview:
SOURCE: Ann Intern Med. 2018 Apr 17. doi: 10.7326/M17-3438.
NEW ORLEANS – Gender inequities may pervade the medical profession, but a new generation of younger physicians – women and men – can help reshape medicine’s mindsets and workplaces.
At the annual meeting of the American College of Physicians, Sue Bornstein, MD, former chief of staff at Baylor University Medical Center in Dallas, and Darilyn Moyer, MD, CEO of the American College of Physicians, talked about the challenges to closing medicine’s gender-equity gaps, from structural bias to backlash. And they outlined strategies for women to broaden career opportunities and achieve fair payment – from mentoring and sponsoring, to leading change from the top of organizations.
The ACP published a position paper on achieving gender equity in the Annals of Internal Medicine.
Dr. Bornstein’s interview:
Dr. Moyer’s interview:
SOURCE: Ann Intern Med. 2018 Apr 17. doi: 10.7326/M17-3438.
NEW ORLEANS – Gender inequities may pervade the medical profession, but a new generation of younger physicians – women and men – can help reshape medicine’s mindsets and workplaces.
At the annual meeting of the American College of Physicians, Sue Bornstein, MD, former chief of staff at Baylor University Medical Center in Dallas, and Darilyn Moyer, MD, CEO of the American College of Physicians, talked about the challenges to closing medicine’s gender-equity gaps, from structural bias to backlash. And they outlined strategies for women to broaden career opportunities and achieve fair payment – from mentoring and sponsoring, to leading change from the top of organizations.
The ACP published a position paper on achieving gender equity in the Annals of Internal Medicine.
Dr. Bornstein’s interview:
Dr. Moyer’s interview:
SOURCE: Ann Intern Med. 2018 Apr 17. doi: 10.7326/M17-3438.
REPORTING FROM ACP Internal Medicine
VIDEO: ZIP code, not gene code – Social factors shape patients’ health
NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.
Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.
When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.
At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.
The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.
Dr. Candler's interview:
Dr. DeSalvo's interview:
Dr. Ende's interview:
SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.
NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.
Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.
When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.
At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.
The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.
Dr. Candler's interview:
Dr. DeSalvo's interview:
Dr. Ende's interview:
SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.
NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.
Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.
When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.
At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.
The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.
Dr. Candler's interview:
Dr. DeSalvo's interview:
Dr. Ende's interview:
SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.
REPORTING FROM ACP INTERNAL MEDICINE
VIDEO: Screening ECG patch boosts AF diagnoses ninefold
ORLANDO – An ECG patch worn twice for a total of about 24 days produced a nearly ninefold increase in the number of high-risk people diagnosed with atrial fibrillation, compared with those followed with usual care in a randomized trial with 2,655 people.
During 4 months of follow-up, 1,364 high-risk people assigned to ECG patch screening had a 5.1% rate of new atrial fibrillation (AF) diagnoses, compared with a 0.6% rate among 1,291 controls who wore the patch but were identified with new-onset AF using standard follow-up that did not take the patch data into account. This was a statistically significant difference for the study’s primary endpoint, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In addition to proving that the ECG patch can better identify asymptomatic people who have AF than conventional means – usually waiting until a stroke occurs or for symptoms to appear – the noninvasive and relatively low-cost patch also gives researchers a new way to try to address the more fundamental medical question created by this line of investigation: How clinically important are relatively brief, asymptomatic episodes of atrial fibrillation, and are patient outcomes improved by treatments begun in this early phase?
The study results “show we can look beyond implantable devices with a less expensive, noninvasive way” to identify patients with asymptomatic AF and determine its natural history and need for intervention, Dr. Steinhubl said in a video interview.
The mSToP (mHealth Screening to Prevent Strokes) trial ran at Scripps and began by identifying more than 359,000 U.S. residents with Aetna health insurance who met the study’s definition of having high AF risk, either by being at least 75 years old, or at least 55 years old and male or at least 65 years old and female. To qualify as high risk those younger than 75 years also had to have at least one clinical risk factor, which could include a prior cerebrovascular event, heart failure, hypertension plus diabetes, obstructive sleep apnea, or any of six other comorbidities. The researchers also excluded potential participants because of several factors, including a history of atrial fibrillation or flutter, current treatment with an anticoagulant, end-stage renal disease, and patients with an implanted pacemaker or defibrillator.
They invited more than 100,000 of these qualifying Aetna beneficiaries to participate, and 2,655 agreed and received by mail a pair of ECG measurement patches (Zio) with instructions to wear one for 2 weeks at the start of the study and to wear the second during the final 2 weeks of the 4-month study period. The participants averaged 73 years of age, and their average CHA2DS2-VASc score was 3.
All patients in the study were told to wear their patches and mail them in, but the researchers used the collected ECG data for diagnosing AF in only the 1,364 patients randomized to the active arm. The ECG findings for the 1,291 controls wasn’t provided to their physicians, and so any new-onset AF had to be found either by symptom onset or incidentally. About one-third of the people assigned to each of the study arms never wore their patches. Those who wore their patches did so for an average of nearly 12 days each. Diagnosis of new-onset AF was based on finding either at least one AF episode recorded by the patches that lasted at least 30 seconds or an AF diagnosis appearing in the patient’s record. The average AF burden – the percentage of time a person with incident AF had an abnormal sinus rhythm – was 0.9%.
Even though many patients did not use their patches, the investigators assessed the primary endpoint of new AF diagnoses during the 4-month study period on an intention-to-treat basis. Their analysis showed an 8.8-fold higher rate of new AF diagnoses among people in the intervention arm whose patch data were used for immediate diagnosis, reported Dr. Steinhubl, an interventional cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Ca.
As a secondary endpoint, the researchers merged the entire group of 1,738 participants who had sent in patches with ECG data and compared their 1-year incidence of diagnosed AF against 3,476 matched controls from the Aetna database. After 1 year, the rate of new AF diagnoses was 6.3% in those with patch information and 2.3% among the controls, a threefold difference in diagnosis rates after adjustment for potential confounders.
“The clinical significance of the short AF episodes” manifested by many patch users identified with AF “requires greater clarity, especially in terms of stroke risk,” Dr. Steinhubl said. But he added, “I like to think that, as we learn more, we can look at more than just anticoagulation” as intervention options. For example, if a morbidly obese patient has asymptomatic AF found by patch screening, it might strengthen the case for bariatric surgery if it’s eventually shown that weight loss after bariatric surgery slows AF progression. The same holds true for more aggressive sleep apnea intervention in patients with sleep apnea and asymptomatic AF, as well as for patients with asymptomatic AF and another type of associated comorbidity.
SOURCE: Steinhubl S. ACC 18, Abstract 402-19.
Results from several studies have now shown that some kind of monitoring for AF in asymptomatic, at-risk people results in an increased diagnosis of subclinical AF. Study results also suggest that, in general, people diagnosed with subclinical AF are at a lower risk of stroke than patients with symptomatic AF. As of now, no prospective study has evaluated the efficacy of anticoagulant therapy in people diagnosed with subclinical AF, although such studies are now in progress. Until we have these results, the question of how to manage patients with subclinical AF remains unanswered.
N.A. Mark Estes, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the mSToPS report.
Results from several studies have now shown that some kind of monitoring for AF in asymptomatic, at-risk people results in an increased diagnosis of subclinical AF. Study results also suggest that, in general, people diagnosed with subclinical AF are at a lower risk of stroke than patients with symptomatic AF. As of now, no prospective study has evaluated the efficacy of anticoagulant therapy in people diagnosed with subclinical AF, although such studies are now in progress. Until we have these results, the question of how to manage patients with subclinical AF remains unanswered.
N.A. Mark Estes, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the mSToPS report.
Results from several studies have now shown that some kind of monitoring for AF in asymptomatic, at-risk people results in an increased diagnosis of subclinical AF. Study results also suggest that, in general, people diagnosed with subclinical AF are at a lower risk of stroke than patients with symptomatic AF. As of now, no prospective study has evaluated the efficacy of anticoagulant therapy in people diagnosed with subclinical AF, although such studies are now in progress. Until we have these results, the question of how to manage patients with subclinical AF remains unanswered.
N.A. Mark Estes, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the mSToPS report.
ORLANDO – An ECG patch worn twice for a total of about 24 days produced a nearly ninefold increase in the number of high-risk people diagnosed with atrial fibrillation, compared with those followed with usual care in a randomized trial with 2,655 people.
During 4 months of follow-up, 1,364 high-risk people assigned to ECG patch screening had a 5.1% rate of new atrial fibrillation (AF) diagnoses, compared with a 0.6% rate among 1,291 controls who wore the patch but were identified with new-onset AF using standard follow-up that did not take the patch data into account. This was a statistically significant difference for the study’s primary endpoint, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In addition to proving that the ECG patch can better identify asymptomatic people who have AF than conventional means – usually waiting until a stroke occurs or for symptoms to appear – the noninvasive and relatively low-cost patch also gives researchers a new way to try to address the more fundamental medical question created by this line of investigation: How clinically important are relatively brief, asymptomatic episodes of atrial fibrillation, and are patient outcomes improved by treatments begun in this early phase?
The study results “show we can look beyond implantable devices with a less expensive, noninvasive way” to identify patients with asymptomatic AF and determine its natural history and need for intervention, Dr. Steinhubl said in a video interview.
The mSToP (mHealth Screening to Prevent Strokes) trial ran at Scripps and began by identifying more than 359,000 U.S. residents with Aetna health insurance who met the study’s definition of having high AF risk, either by being at least 75 years old, or at least 55 years old and male or at least 65 years old and female. To qualify as high risk those younger than 75 years also had to have at least one clinical risk factor, which could include a prior cerebrovascular event, heart failure, hypertension plus diabetes, obstructive sleep apnea, or any of six other comorbidities. The researchers also excluded potential participants because of several factors, including a history of atrial fibrillation or flutter, current treatment with an anticoagulant, end-stage renal disease, and patients with an implanted pacemaker or defibrillator.
They invited more than 100,000 of these qualifying Aetna beneficiaries to participate, and 2,655 agreed and received by mail a pair of ECG measurement patches (Zio) with instructions to wear one for 2 weeks at the start of the study and to wear the second during the final 2 weeks of the 4-month study period. The participants averaged 73 years of age, and their average CHA2DS2-VASc score was 3.
All patients in the study were told to wear their patches and mail them in, but the researchers used the collected ECG data for diagnosing AF in only the 1,364 patients randomized to the active arm. The ECG findings for the 1,291 controls wasn’t provided to their physicians, and so any new-onset AF had to be found either by symptom onset or incidentally. About one-third of the people assigned to each of the study arms never wore their patches. Those who wore their patches did so for an average of nearly 12 days each. Diagnosis of new-onset AF was based on finding either at least one AF episode recorded by the patches that lasted at least 30 seconds or an AF diagnosis appearing in the patient’s record. The average AF burden – the percentage of time a person with incident AF had an abnormal sinus rhythm – was 0.9%.
Even though many patients did not use their patches, the investigators assessed the primary endpoint of new AF diagnoses during the 4-month study period on an intention-to-treat basis. Their analysis showed an 8.8-fold higher rate of new AF diagnoses among people in the intervention arm whose patch data were used for immediate diagnosis, reported Dr. Steinhubl, an interventional cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Ca.
As a secondary endpoint, the researchers merged the entire group of 1,738 participants who had sent in patches with ECG data and compared their 1-year incidence of diagnosed AF against 3,476 matched controls from the Aetna database. After 1 year, the rate of new AF diagnoses was 6.3% in those with patch information and 2.3% among the controls, a threefold difference in diagnosis rates after adjustment for potential confounders.
“The clinical significance of the short AF episodes” manifested by many patch users identified with AF “requires greater clarity, especially in terms of stroke risk,” Dr. Steinhubl said. But he added, “I like to think that, as we learn more, we can look at more than just anticoagulation” as intervention options. For example, if a morbidly obese patient has asymptomatic AF found by patch screening, it might strengthen the case for bariatric surgery if it’s eventually shown that weight loss after bariatric surgery slows AF progression. The same holds true for more aggressive sleep apnea intervention in patients with sleep apnea and asymptomatic AF, as well as for patients with asymptomatic AF and another type of associated comorbidity.
SOURCE: Steinhubl S. ACC 18, Abstract 402-19.
ORLANDO – An ECG patch worn twice for a total of about 24 days produced a nearly ninefold increase in the number of high-risk people diagnosed with atrial fibrillation, compared with those followed with usual care in a randomized trial with 2,655 people.
During 4 months of follow-up, 1,364 high-risk people assigned to ECG patch screening had a 5.1% rate of new atrial fibrillation (AF) diagnoses, compared with a 0.6% rate among 1,291 controls who wore the patch but were identified with new-onset AF using standard follow-up that did not take the patch data into account. This was a statistically significant difference for the study’s primary endpoint, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In addition to proving that the ECG patch can better identify asymptomatic people who have AF than conventional means – usually waiting until a stroke occurs or for symptoms to appear – the noninvasive and relatively low-cost patch also gives researchers a new way to try to address the more fundamental medical question created by this line of investigation: How clinically important are relatively brief, asymptomatic episodes of atrial fibrillation, and are patient outcomes improved by treatments begun in this early phase?
The study results “show we can look beyond implantable devices with a less expensive, noninvasive way” to identify patients with asymptomatic AF and determine its natural history and need for intervention, Dr. Steinhubl said in a video interview.
The mSToP (mHealth Screening to Prevent Strokes) trial ran at Scripps and began by identifying more than 359,000 U.S. residents with Aetna health insurance who met the study’s definition of having high AF risk, either by being at least 75 years old, or at least 55 years old and male or at least 65 years old and female. To qualify as high risk those younger than 75 years also had to have at least one clinical risk factor, which could include a prior cerebrovascular event, heart failure, hypertension plus diabetes, obstructive sleep apnea, or any of six other comorbidities. The researchers also excluded potential participants because of several factors, including a history of atrial fibrillation or flutter, current treatment with an anticoagulant, end-stage renal disease, and patients with an implanted pacemaker or defibrillator.
They invited more than 100,000 of these qualifying Aetna beneficiaries to participate, and 2,655 agreed and received by mail a pair of ECG measurement patches (Zio) with instructions to wear one for 2 weeks at the start of the study and to wear the second during the final 2 weeks of the 4-month study period. The participants averaged 73 years of age, and their average CHA2DS2-VASc score was 3.
All patients in the study were told to wear their patches and mail them in, but the researchers used the collected ECG data for diagnosing AF in only the 1,364 patients randomized to the active arm. The ECG findings for the 1,291 controls wasn’t provided to their physicians, and so any new-onset AF had to be found either by symptom onset or incidentally. About one-third of the people assigned to each of the study arms never wore their patches. Those who wore their patches did so for an average of nearly 12 days each. Diagnosis of new-onset AF was based on finding either at least one AF episode recorded by the patches that lasted at least 30 seconds or an AF diagnosis appearing in the patient’s record. The average AF burden – the percentage of time a person with incident AF had an abnormal sinus rhythm – was 0.9%.
Even though many patients did not use their patches, the investigators assessed the primary endpoint of new AF diagnoses during the 4-month study period on an intention-to-treat basis. Their analysis showed an 8.8-fold higher rate of new AF diagnoses among people in the intervention arm whose patch data were used for immediate diagnosis, reported Dr. Steinhubl, an interventional cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Ca.
As a secondary endpoint, the researchers merged the entire group of 1,738 participants who had sent in patches with ECG data and compared their 1-year incidence of diagnosed AF against 3,476 matched controls from the Aetna database. After 1 year, the rate of new AF diagnoses was 6.3% in those with patch information and 2.3% among the controls, a threefold difference in diagnosis rates after adjustment for potential confounders.
“The clinical significance of the short AF episodes” manifested by many patch users identified with AF “requires greater clarity, especially in terms of stroke risk,” Dr. Steinhubl said. But he added, “I like to think that, as we learn more, we can look at more than just anticoagulation” as intervention options. For example, if a morbidly obese patient has asymptomatic AF found by patch screening, it might strengthen the case for bariatric surgery if it’s eventually shown that weight loss after bariatric surgery slows AF progression. The same holds true for more aggressive sleep apnea intervention in patients with sleep apnea and asymptomatic AF, as well as for patients with asymptomatic AF and another type of associated comorbidity.
SOURCE: Steinhubl S. ACC 18, Abstract 402-19.
REPORTING FROM ACC 18
Key clinical point: .
Major finding: After 4 months, new AF diagnoses occurred in 5.1% of patch users and 0.6% of usual-care controls.
Study details: mSToPS, a single-center, randomized study with 2,655 people at high risk for developing AF.
Disclosures: mSToPS received support from Aetna, Janssen, and iRhythm. Dr. Steinhubl has been an advisor to Airstrip, DynoSense, EasyG, FocusMotion, LifeWatch, MyoKardia, Novartis, and Spry Health, he serves on the board of Celes Health, and he has received research support from Janssen and Novartis.
Source: Steinhubl S. ACC 18, Abstract 402-19.
VIDEO: Triple-antihypertensive pill nails early therapy
ORLANDO – Hypertensive adults started on a triple-drug, single daily pill regimen as either initial or early treatment had a sharply better rate of reaching their goal blood pressure after 6 months, compared with usual-care controls, in a multicenter, randomized trial with 700 patients.
“Early use of a low-dose, three-in-one blood pressure lowering pill is safe and provides faster and better control of blood pressure compared with usual care,” Ruth Webster, PhD, said at the annual meeting of the American College of Cardiology.
The tested polypill contained half the standard doses of the angiotensin receptor blocker telmisartan (20 mg), the calcium channel blocker amlodipine (2.5 mg), and the diuretic chlorthalidone (12.5 mg). After 6 months on this regimen, 70% of patients were at their goal blood pressure, compared with 55% of the control patients, and patients on the polypill had on average a 10/5 mm Hg greater reduction in their blood pressure than did patients on usual care, reported Dr. Webster, head of research programs at the George Institute for Global Health in Sydney. Rates of total and serious adverse events and withdrawals because of adverse events were similar in the two study arms, and both arms also had nearly identical levels of treatment adherence, about 95%.
“No prior trial has evaluated a triple, low-dose pill for initial or early treatment,” she noted.
“This is a home run,” said Karol E. Watson, MD, professor of medicine and director of the Women’s Cardiovascular Health Center at the University of California, Los Angeles. “In the past, clinicians were told to pick one drug and push it as hard as you could and then maybe think about adding a second drug. Experience has shown that this does not increase efficacy, but it does increase adverse events, so current guidelines say start with two drugs. Now they are showing for the first time that you should start with three drugs. That goes with what we know.”
“Triple-drug therapy for the masses makes complete sense,” especially now that the blood pressure goal for most patients is less than 130/80 mm Hg, said William B. White, MD, professor of medicine and chief of hypertension and clinical pharmacology at the University of Connecticut in Farmington. Plus, “compliance is vastly improved when you use a combination-drug pill,” he noted.
The blood pressure targets that Dr. Webster and her associates used were less than 140/90 mm Hg except in patients with diabetes or chronic kidney disease, who had a target of less than 130/80 mm Hg. At the time researchers designed the trial the generally accepted blood pressure target for antihypertensive treatment was less than 140/90 mm Hg, Dr. Webster noted.
She also stressed that she did not believe the three specific drugs selected for the polypill made a difference. “The specific drugs we used was not that important. We would probably get the same result with different drugs. It’s about the strategy of using triple, low-dose therapy,” Dr. Webster suggested. Dr. Watson agreed.
The TRIUMPH (Triple Pill vs. Usual Care Management for Patients with Mild to Moderate Hypertension) study enrolled patients at 11 hospital outpatient clinics in Sri Lanka. The average age of the patients was 56 years. The average blood pressure was 154/90 mm Hg. About 59% of patients were not on any antihypertensive drug at baseline, with the rest on a single drug. The study protocol excluded patients on two or more drugs at entry. Roughly 30% of enrolled patients had diabetes, and 1%-2% had chronic kidney disease. Their target blood pressure on treatment during the study was less than 130/80 mm Hg.
The study’s primary endpoint was the percentage of patients at their goal blood pressure after 6 months. Patients in the triple-drug polypill group achieved their goal blood pressure 23% more often relative to the control, usual care patients, a statistically significant difference. The between group difference in achievement of goal blood pressure was apparent by the end of the first 6 weeks in the study. Patients in the control arm generally received either one or two drugs during the study, but often at full dose rather than the half doses used in the triple-drug patients. The study’s design specified that patients in the triple-drug arm who were not at their target blood pressure after 6 weeks could, at the discretion of their treating physician, switch to a second formulation that doubled the dosage of each of the three drugs. Patients in the usual care arm could have their treatment adjusted after 6 or 12 weeks as long as they continued to receive either one or two drugs. After 6 weeks, 68% of patients in the triple-drug arm and 44% receiving usual care were at their blood pressure goal. After 12 weeks, the percentages at goal were 73% of patients on the triple-drug pill and 47% on usual care.
Dr. Webster hypothesized that the triple-drug, low-dose strategy for initial or early treatment would surpass usual care not only in low- and middle-income countries, like Sri Lanka, but also in high-income, industrialized countries such as the United States.
TRIUMPH received no commercial funding. Dr. Webster had no disclosures. Dr. Watson has been a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and GlaxoSmithKline. Dr. White has been a consultant to Novartis.
SOURCE: Webster R. ACC 2018. Webster R et al. ACC 18 late breaker.
The TRIUMPH results showed the feasibility and efficacy of achieving good blood pressure control with a single pill containing low doses of three different antihypertensive drugs that are well tolerated and have different mechanisms of action. This strategy avoids the adverse effects from drugs used at their maximum dose.
An attraction of this strategy is how seamless it is for patients. They take a single pill with three drugs, which can enhance compliance and in routine practice can reduce their copay. It’s much easier for patients to take a single pill.
Eileen M. Handberg, PhD , is a research professor of medicine and director of the Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
The TRIUMPH results showed the feasibility and efficacy of achieving good blood pressure control with a single pill containing low doses of three different antihypertensive drugs that are well tolerated and have different mechanisms of action. This strategy avoids the adverse effects from drugs used at their maximum dose.
An attraction of this strategy is how seamless it is for patients. They take a single pill with three drugs, which can enhance compliance and in routine practice can reduce their copay. It’s much easier for patients to take a single pill.
Eileen M. Handberg, PhD , is a research professor of medicine and director of the Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
The TRIUMPH results showed the feasibility and efficacy of achieving good blood pressure control with a single pill containing low doses of three different antihypertensive drugs that are well tolerated and have different mechanisms of action. This strategy avoids the adverse effects from drugs used at their maximum dose.
An attraction of this strategy is how seamless it is for patients. They take a single pill with three drugs, which can enhance compliance and in routine practice can reduce their copay. It’s much easier for patients to take a single pill.
Eileen M. Handberg, PhD , is a research professor of medicine and director of the Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
ORLANDO – Hypertensive adults started on a triple-drug, single daily pill regimen as either initial or early treatment had a sharply better rate of reaching their goal blood pressure after 6 months, compared with usual-care controls, in a multicenter, randomized trial with 700 patients.
“Early use of a low-dose, three-in-one blood pressure lowering pill is safe and provides faster and better control of blood pressure compared with usual care,” Ruth Webster, PhD, said at the annual meeting of the American College of Cardiology.
The tested polypill contained half the standard doses of the angiotensin receptor blocker telmisartan (20 mg), the calcium channel blocker amlodipine (2.5 mg), and the diuretic chlorthalidone (12.5 mg). After 6 months on this regimen, 70% of patients were at their goal blood pressure, compared with 55% of the control patients, and patients on the polypill had on average a 10/5 mm Hg greater reduction in their blood pressure than did patients on usual care, reported Dr. Webster, head of research programs at the George Institute for Global Health in Sydney. Rates of total and serious adverse events and withdrawals because of adverse events were similar in the two study arms, and both arms also had nearly identical levels of treatment adherence, about 95%.
“No prior trial has evaluated a triple, low-dose pill for initial or early treatment,” she noted.
“This is a home run,” said Karol E. Watson, MD, professor of medicine and director of the Women’s Cardiovascular Health Center at the University of California, Los Angeles. “In the past, clinicians were told to pick one drug and push it as hard as you could and then maybe think about adding a second drug. Experience has shown that this does not increase efficacy, but it does increase adverse events, so current guidelines say start with two drugs. Now they are showing for the first time that you should start with three drugs. That goes with what we know.”
“Triple-drug therapy for the masses makes complete sense,” especially now that the blood pressure goal for most patients is less than 130/80 mm Hg, said William B. White, MD, professor of medicine and chief of hypertension and clinical pharmacology at the University of Connecticut in Farmington. Plus, “compliance is vastly improved when you use a combination-drug pill,” he noted.
The blood pressure targets that Dr. Webster and her associates used were less than 140/90 mm Hg except in patients with diabetes or chronic kidney disease, who had a target of less than 130/80 mm Hg. At the time researchers designed the trial the generally accepted blood pressure target for antihypertensive treatment was less than 140/90 mm Hg, Dr. Webster noted.
She also stressed that she did not believe the three specific drugs selected for the polypill made a difference. “The specific drugs we used was not that important. We would probably get the same result with different drugs. It’s about the strategy of using triple, low-dose therapy,” Dr. Webster suggested. Dr. Watson agreed.
The TRIUMPH (Triple Pill vs. Usual Care Management for Patients with Mild to Moderate Hypertension) study enrolled patients at 11 hospital outpatient clinics in Sri Lanka. The average age of the patients was 56 years. The average blood pressure was 154/90 mm Hg. About 59% of patients were not on any antihypertensive drug at baseline, with the rest on a single drug. The study protocol excluded patients on two or more drugs at entry. Roughly 30% of enrolled patients had diabetes, and 1%-2% had chronic kidney disease. Their target blood pressure on treatment during the study was less than 130/80 mm Hg.
The study’s primary endpoint was the percentage of patients at their goal blood pressure after 6 months. Patients in the triple-drug polypill group achieved their goal blood pressure 23% more often relative to the control, usual care patients, a statistically significant difference. The between group difference in achievement of goal blood pressure was apparent by the end of the first 6 weeks in the study. Patients in the control arm generally received either one or two drugs during the study, but often at full dose rather than the half doses used in the triple-drug patients. The study’s design specified that patients in the triple-drug arm who were not at their target blood pressure after 6 weeks could, at the discretion of their treating physician, switch to a second formulation that doubled the dosage of each of the three drugs. Patients in the usual care arm could have their treatment adjusted after 6 or 12 weeks as long as they continued to receive either one or two drugs. After 6 weeks, 68% of patients in the triple-drug arm and 44% receiving usual care were at their blood pressure goal. After 12 weeks, the percentages at goal were 73% of patients on the triple-drug pill and 47% on usual care.
Dr. Webster hypothesized that the triple-drug, low-dose strategy for initial or early treatment would surpass usual care not only in low- and middle-income countries, like Sri Lanka, but also in high-income, industrialized countries such as the United States.
TRIUMPH received no commercial funding. Dr. Webster had no disclosures. Dr. Watson has been a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and GlaxoSmithKline. Dr. White has been a consultant to Novartis.
SOURCE: Webster R. ACC 2018. Webster R et al. ACC 18 late breaker.
ORLANDO – Hypertensive adults started on a triple-drug, single daily pill regimen as either initial or early treatment had a sharply better rate of reaching their goal blood pressure after 6 months, compared with usual-care controls, in a multicenter, randomized trial with 700 patients.
“Early use of a low-dose, three-in-one blood pressure lowering pill is safe and provides faster and better control of blood pressure compared with usual care,” Ruth Webster, PhD, said at the annual meeting of the American College of Cardiology.
The tested polypill contained half the standard doses of the angiotensin receptor blocker telmisartan (20 mg), the calcium channel blocker amlodipine (2.5 mg), and the diuretic chlorthalidone (12.5 mg). After 6 months on this regimen, 70% of patients were at their goal blood pressure, compared with 55% of the control patients, and patients on the polypill had on average a 10/5 mm Hg greater reduction in their blood pressure than did patients on usual care, reported Dr. Webster, head of research programs at the George Institute for Global Health in Sydney. Rates of total and serious adverse events and withdrawals because of adverse events were similar in the two study arms, and both arms also had nearly identical levels of treatment adherence, about 95%.
“No prior trial has evaluated a triple, low-dose pill for initial or early treatment,” she noted.
“This is a home run,” said Karol E. Watson, MD, professor of medicine and director of the Women’s Cardiovascular Health Center at the University of California, Los Angeles. “In the past, clinicians were told to pick one drug and push it as hard as you could and then maybe think about adding a second drug. Experience has shown that this does not increase efficacy, but it does increase adverse events, so current guidelines say start with two drugs. Now they are showing for the first time that you should start with three drugs. That goes with what we know.”
“Triple-drug therapy for the masses makes complete sense,” especially now that the blood pressure goal for most patients is less than 130/80 mm Hg, said William B. White, MD, professor of medicine and chief of hypertension and clinical pharmacology at the University of Connecticut in Farmington. Plus, “compliance is vastly improved when you use a combination-drug pill,” he noted.
The blood pressure targets that Dr. Webster and her associates used were less than 140/90 mm Hg except in patients with diabetes or chronic kidney disease, who had a target of less than 130/80 mm Hg. At the time researchers designed the trial the generally accepted blood pressure target for antihypertensive treatment was less than 140/90 mm Hg, Dr. Webster noted.
She also stressed that she did not believe the three specific drugs selected for the polypill made a difference. “The specific drugs we used was not that important. We would probably get the same result with different drugs. It’s about the strategy of using triple, low-dose therapy,” Dr. Webster suggested. Dr. Watson agreed.
The TRIUMPH (Triple Pill vs. Usual Care Management for Patients with Mild to Moderate Hypertension) study enrolled patients at 11 hospital outpatient clinics in Sri Lanka. The average age of the patients was 56 years. The average blood pressure was 154/90 mm Hg. About 59% of patients were not on any antihypertensive drug at baseline, with the rest on a single drug. The study protocol excluded patients on two or more drugs at entry. Roughly 30% of enrolled patients had diabetes, and 1%-2% had chronic kidney disease. Their target blood pressure on treatment during the study was less than 130/80 mm Hg.
The study’s primary endpoint was the percentage of patients at their goal blood pressure after 6 months. Patients in the triple-drug polypill group achieved their goal blood pressure 23% more often relative to the control, usual care patients, a statistically significant difference. The between group difference in achievement of goal blood pressure was apparent by the end of the first 6 weeks in the study. Patients in the control arm generally received either one or two drugs during the study, but often at full dose rather than the half doses used in the triple-drug patients. The study’s design specified that patients in the triple-drug arm who were not at their target blood pressure after 6 weeks could, at the discretion of their treating physician, switch to a second formulation that doubled the dosage of each of the three drugs. Patients in the usual care arm could have their treatment adjusted after 6 or 12 weeks as long as they continued to receive either one or two drugs. After 6 weeks, 68% of patients in the triple-drug arm and 44% receiving usual care were at their blood pressure goal. After 12 weeks, the percentages at goal were 73% of patients on the triple-drug pill and 47% on usual care.
Dr. Webster hypothesized that the triple-drug, low-dose strategy for initial or early treatment would surpass usual care not only in low- and middle-income countries, like Sri Lanka, but also in high-income, industrialized countries such as the United States.
TRIUMPH received no commercial funding. Dr. Webster had no disclosures. Dr. Watson has been a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and GlaxoSmithKline. Dr. White has been a consultant to Novartis.
SOURCE: Webster R. ACC 2018. Webster R et al. ACC 18 late breaker.
REPORTING FROM ACC 18
Key clinical point: Starting hypertensive patients on a single, triple-drug pill produced excellent control.
Major finding: After 6 months, 70% of patients on the triple-drug pill reached target blood pressure, compared with 55% of control patients.
Study details: TRIUMPH, a multicenter, randomized trial with 700 hypertensive adults.
Disclosures: TRIUMPH received no commercial funding. Dr. Webster had no disclosures. Dr. Watson has been a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and GlaxoSmithKline. Dr. White has been a consultant to Novartis.
Source: Webster R et al. ACC 18 late breaker.
VIDEO: Cervical cancer laparotomy outperforms minimally invasive surgery
NEW ORLEANS – Use of minimally invasive radical hysterectomy to treat early-stage cervical cancer has grown over the past decade, and in current U.S. practice, roughly half of these cases are done with a minimally-invasive approach, with the rest done by conventional laparotomy. But the first data ever reported from a large, prospective trial that compared the efficacy of both methods for cervical cancer had the unexpected finding that disease-free survival following minimally invasive procedures significantly lagged behind radical hysterectomies done by open laparotomy, Pedro T. Ramirez, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Just after this report came results from a second study that used propensity score–adjusted observational data from the National Cancer Database and found significantly worse overall survival following minimally invasive radical hysterectomy for early-stage cervical cancer, compared with laparotomy, said J. Alejandro Rauh-Hain, MD, a gynecologic oncologist at the University of Texas MD Anderson Cancer Center in Houston.
Both findings were “very surprising,” said Dr. Rauh-Hain in a video interview. “I was pretty sure we’d see no difference” in outcomes between minimally invasive radical hysterectomies and the same surgery either done by laparoscope or robotically assisted.
Prior prospective comparisons of minimally invasive and open surgical methods for other cancer types, including endometrial, gastric, and ovarian, showed no differences in cancer recurrences and survival, which led to widening use of minimally invasive surgery (MIS) for cervical cancer despite no direct evidence supporting equivalence, Dr. Rauh-Hain noted. “We adopted it with no data. It made sense that cervical cancer would be the same as endometrial cancer,” he explained.
The Laparoscopic Approach to Cervical Cancer (LACC) trial ran at 33 centers in 12 countries, including six U.S. centers. The study randomized women during 2008-2017 who had stage 1A1, 1A2, or 1B1 cervical cancer to either MIS or open surgery for a radical hysterectomy. Each participating center had to submit to a trial review committee full case records for 10 patients and unedited surgical videos of two patients who had previously undergone a minimally invasive radical hysterectomy at the center to document local prowess with MIS.
Dr. Ramirez and his colleagues designed LACC to prove the noninferiority of MIS and calculated an expected enrollment of 740 patients based on statistical expectations, but the study stopped early after enrolling 631 patients because of the adverse outcomes identified in the MIS patients, with a median follow-up of 2.5 years instead of the planned follow-up of 4.5 years. The study reached the 4.5-year follow-up in about 39% of patients. Of the 312 patients randomized to undergo laparotomy, 88% actually underwent the surgery; of the 319 patients randomized to MIS, 91% received this surgery, with 16% of the MIS procedures done using robotic assistance.
The study’s primary endpoint was disease-free survival at 4.5 years, which occurred in 86% of the MIS patients and in 96.5% of the laparotomy patients, a difference that failed to meet the study’s prespecified definition of noninferiority for MIS, reported Dr. Ramirez, a professor of gynecologic oncology and director of Minimally Invasive Surgery Research and Education at the MD Anderson Cancer Center. In addition, several secondary analyses of the data all showed starkly superior outcomes in the laparotomy subgroup.
Disease-free survival among all patients regardless of follow-up duration occurred in 98% of laparotomy patients and 92% of MIS patients, which translated into a 3.74 hazard ratio (P = .002) for disease recurrence or death among the MIS patients when compared with laparotomy patients. The all-cause mortality rates were 1% in the laparotomy patients and 6% among the MIS patients, a hazard ratio of 6.00 (P = .004). The risk of local or regional recurrences was more than fourfold higher in the MIS patients. A blinded, central panel adjudicated all recurrences identified during the study.
The LACC results “should be discussed with patients scheduled to undergo radical hysterectomy” for cervical cancer, Dr. Ramirez concluded.
The observational data from the National Cancer Database used in the analysis led by Dr. Rauh-Hain came from 2,221 patients hospitalized and treated with radical hysterectomy and pelvic lymph node dissection at a U.S. center during 2010-2012 for either stage 1A2 or 1B1 cervical cancer. Among these patients, 47.5% underwent MIS, with 79% of those procedures done with robotic assistance, while the other 52.5% underwent open laparotomy, Dr. Rauh-Hain reported. Additional analysis of data from this database by the researchers showed that, although the first report of MIS for radical hysterectomy appeared in 1992, the approach remained largely unused in U.S. practice until 2007, when use of MIS began to sharply rise. By 2010, about a third of radical hysterectomies for cervical cancer involved MIS, and usage increased still further during 2011 and 2012 to produce a nearly 48% rate during the 3-year study period.
The primary endpoint of Dr. Rauh-Hain’s analysis was overall survival following propensity-score matching of the MIS and laparotomy patients using 13 demographic and clinical criteria. The analysis showed 4-year mortality rates of 5.8% among the laparotomy patients and 8.4% among the MIS patients, which calculated to a relatively increased mortality hazard from MIS of 48% (P = .02).
Dr. Rauh-Hain also reported results from an interrupted time series analysis using data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. This analysis compared annual 4-year relative survival rates among women undergoing radical hysterectomy for cervical cancer and found that, after survival rates showed a gradual, steady rise during the years culminating in 2006, once MIS began being more widely used in 2007 survival rates began to drop, with a statistically significant annualized decline of 1% through 2010.
Based on the results from both studies, “at MD Anderson we discuss the results with patients,” with the consequence that the percentage of patients treated with laparotomy is now increasing, Dr. Rauh-Hain said. The results from both studies “are concerning,” he explained.
SOURCE: Ramirez PT and Rauh-Hain JA. SGO 2018, Late-Breaking Abstracts 1 and 2.
The findings from these studies appear valid and should be discussed with patients.
The findings raise a major question: Why has minimally invasive surgery (MIS) led to worse survival rates than laparotomy? Several possible explanations can be hypothesized: The uterine manipulator used in MIS led to local spread of cancer cells; MIS involves a learning curve and initial attempts at MIS did not remove enough of the tumor; and MIS led to increased exposure of the peritoneal cavity to the cancer. The findings also raise another question: Why has MIS for cervical cancer performed less well than MIS for cancers from other organs, such as endometrial and prostate?
The overall survival results from the LACC trial calculate out to 4.75 added deaths per year for every 1,000 patients treated with MIS, compared with laparoscopy. But the National Inpatient Sample data suggest that MIS cuts mortality by about two deaths per year per 1,000 patients, compared with laparotomy, and mortality data from a different analysis (Gynecol Oncol. 2012 Oct;127[1]:11-7) suggest that MIS might prevent six deaths annually for every 1,000 patients, compared with laparotomy. Overall, these three sets of findings suggest roughly comparable mortality outcomes from MIS and laparotomy, but with MIS having the bonus of fewer complications and less need for transfusions.
The cautions and concerns raised by the LACC trial and Dr. Rauh-Hain’s analysis of observational data cannot be easily dismissed. We need to figure out why the results from both studies show worse survival and recurrence rates with MIS, and we need to identify whether subgroups of patients exist who might clearly benefit from either the MIS or open-surgery approach.
Shitanshu Uppal, MD , is a gynecologic oncologist at the University of Michigan in Ann Arbor. He made these comments as designated discussant for the two studies. He had no disclosures.
The findings from these studies appear valid and should be discussed with patients.
The findings raise a major question: Why has minimally invasive surgery (MIS) led to worse survival rates than laparotomy? Several possible explanations can be hypothesized: The uterine manipulator used in MIS led to local spread of cancer cells; MIS involves a learning curve and initial attempts at MIS did not remove enough of the tumor; and MIS led to increased exposure of the peritoneal cavity to the cancer. The findings also raise another question: Why has MIS for cervical cancer performed less well than MIS for cancers from other organs, such as endometrial and prostate?
The overall survival results from the LACC trial calculate out to 4.75 added deaths per year for every 1,000 patients treated with MIS, compared with laparoscopy. But the National Inpatient Sample data suggest that MIS cuts mortality by about two deaths per year per 1,000 patients, compared with laparotomy, and mortality data from a different analysis (Gynecol Oncol. 2012 Oct;127[1]:11-7) suggest that MIS might prevent six deaths annually for every 1,000 patients, compared with laparotomy. Overall, these three sets of findings suggest roughly comparable mortality outcomes from MIS and laparotomy, but with MIS having the bonus of fewer complications and less need for transfusions.
The cautions and concerns raised by the LACC trial and Dr. Rauh-Hain’s analysis of observational data cannot be easily dismissed. We need to figure out why the results from both studies show worse survival and recurrence rates with MIS, and we need to identify whether subgroups of patients exist who might clearly benefit from either the MIS or open-surgery approach.
Shitanshu Uppal, MD , is a gynecologic oncologist at the University of Michigan in Ann Arbor. He made these comments as designated discussant for the two studies. He had no disclosures.
The findings from these studies appear valid and should be discussed with patients.
The findings raise a major question: Why has minimally invasive surgery (MIS) led to worse survival rates than laparotomy? Several possible explanations can be hypothesized: The uterine manipulator used in MIS led to local spread of cancer cells; MIS involves a learning curve and initial attempts at MIS did not remove enough of the tumor; and MIS led to increased exposure of the peritoneal cavity to the cancer. The findings also raise another question: Why has MIS for cervical cancer performed less well than MIS for cancers from other organs, such as endometrial and prostate?
The overall survival results from the LACC trial calculate out to 4.75 added deaths per year for every 1,000 patients treated with MIS, compared with laparoscopy. But the National Inpatient Sample data suggest that MIS cuts mortality by about two deaths per year per 1,000 patients, compared with laparotomy, and mortality data from a different analysis (Gynecol Oncol. 2012 Oct;127[1]:11-7) suggest that MIS might prevent six deaths annually for every 1,000 patients, compared with laparotomy. Overall, these three sets of findings suggest roughly comparable mortality outcomes from MIS and laparotomy, but with MIS having the bonus of fewer complications and less need for transfusions.
The cautions and concerns raised by the LACC trial and Dr. Rauh-Hain’s analysis of observational data cannot be easily dismissed. We need to figure out why the results from both studies show worse survival and recurrence rates with MIS, and we need to identify whether subgroups of patients exist who might clearly benefit from either the MIS or open-surgery approach.
Shitanshu Uppal, MD , is a gynecologic oncologist at the University of Michigan in Ann Arbor. He made these comments as designated discussant for the two studies. He had no disclosures.
NEW ORLEANS – Use of minimally invasive radical hysterectomy to treat early-stage cervical cancer has grown over the past decade, and in current U.S. practice, roughly half of these cases are done with a minimally-invasive approach, with the rest done by conventional laparotomy. But the first data ever reported from a large, prospective trial that compared the efficacy of both methods for cervical cancer had the unexpected finding that disease-free survival following minimally invasive procedures significantly lagged behind radical hysterectomies done by open laparotomy, Pedro T. Ramirez, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Just after this report came results from a second study that used propensity score–adjusted observational data from the National Cancer Database and found significantly worse overall survival following minimally invasive radical hysterectomy for early-stage cervical cancer, compared with laparotomy, said J. Alejandro Rauh-Hain, MD, a gynecologic oncologist at the University of Texas MD Anderson Cancer Center in Houston.
Both findings were “very surprising,” said Dr. Rauh-Hain in a video interview. “I was pretty sure we’d see no difference” in outcomes between minimally invasive radical hysterectomies and the same surgery either done by laparoscope or robotically assisted.
Prior prospective comparisons of minimally invasive and open surgical methods for other cancer types, including endometrial, gastric, and ovarian, showed no differences in cancer recurrences and survival, which led to widening use of minimally invasive surgery (MIS) for cervical cancer despite no direct evidence supporting equivalence, Dr. Rauh-Hain noted. “We adopted it with no data. It made sense that cervical cancer would be the same as endometrial cancer,” he explained.
The Laparoscopic Approach to Cervical Cancer (LACC) trial ran at 33 centers in 12 countries, including six U.S. centers. The study randomized women during 2008-2017 who had stage 1A1, 1A2, or 1B1 cervical cancer to either MIS or open surgery for a radical hysterectomy. Each participating center had to submit to a trial review committee full case records for 10 patients and unedited surgical videos of two patients who had previously undergone a minimally invasive radical hysterectomy at the center to document local prowess with MIS.
Dr. Ramirez and his colleagues designed LACC to prove the noninferiority of MIS and calculated an expected enrollment of 740 patients based on statistical expectations, but the study stopped early after enrolling 631 patients because of the adverse outcomes identified in the MIS patients, with a median follow-up of 2.5 years instead of the planned follow-up of 4.5 years. The study reached the 4.5-year follow-up in about 39% of patients. Of the 312 patients randomized to undergo laparotomy, 88% actually underwent the surgery; of the 319 patients randomized to MIS, 91% received this surgery, with 16% of the MIS procedures done using robotic assistance.
The study’s primary endpoint was disease-free survival at 4.5 years, which occurred in 86% of the MIS patients and in 96.5% of the laparotomy patients, a difference that failed to meet the study’s prespecified definition of noninferiority for MIS, reported Dr. Ramirez, a professor of gynecologic oncology and director of Minimally Invasive Surgery Research and Education at the MD Anderson Cancer Center. In addition, several secondary analyses of the data all showed starkly superior outcomes in the laparotomy subgroup.
Disease-free survival among all patients regardless of follow-up duration occurred in 98% of laparotomy patients and 92% of MIS patients, which translated into a 3.74 hazard ratio (P = .002) for disease recurrence or death among the MIS patients when compared with laparotomy patients. The all-cause mortality rates were 1% in the laparotomy patients and 6% among the MIS patients, a hazard ratio of 6.00 (P = .004). The risk of local or regional recurrences was more than fourfold higher in the MIS patients. A blinded, central panel adjudicated all recurrences identified during the study.
The LACC results “should be discussed with patients scheduled to undergo radical hysterectomy” for cervical cancer, Dr. Ramirez concluded.
The observational data from the National Cancer Database used in the analysis led by Dr. Rauh-Hain came from 2,221 patients hospitalized and treated with radical hysterectomy and pelvic lymph node dissection at a U.S. center during 2010-2012 for either stage 1A2 or 1B1 cervical cancer. Among these patients, 47.5% underwent MIS, with 79% of those procedures done with robotic assistance, while the other 52.5% underwent open laparotomy, Dr. Rauh-Hain reported. Additional analysis of data from this database by the researchers showed that, although the first report of MIS for radical hysterectomy appeared in 1992, the approach remained largely unused in U.S. practice until 2007, when use of MIS began to sharply rise. By 2010, about a third of radical hysterectomies for cervical cancer involved MIS, and usage increased still further during 2011 and 2012 to produce a nearly 48% rate during the 3-year study period.
The primary endpoint of Dr. Rauh-Hain’s analysis was overall survival following propensity-score matching of the MIS and laparotomy patients using 13 demographic and clinical criteria. The analysis showed 4-year mortality rates of 5.8% among the laparotomy patients and 8.4% among the MIS patients, which calculated to a relatively increased mortality hazard from MIS of 48% (P = .02).
Dr. Rauh-Hain also reported results from an interrupted time series analysis using data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. This analysis compared annual 4-year relative survival rates among women undergoing radical hysterectomy for cervical cancer and found that, after survival rates showed a gradual, steady rise during the years culminating in 2006, once MIS began being more widely used in 2007 survival rates began to drop, with a statistically significant annualized decline of 1% through 2010.
Based on the results from both studies, “at MD Anderson we discuss the results with patients,” with the consequence that the percentage of patients treated with laparotomy is now increasing, Dr. Rauh-Hain said. The results from both studies “are concerning,” he explained.
SOURCE: Ramirez PT and Rauh-Hain JA. SGO 2018, Late-Breaking Abstracts 1 and 2.
NEW ORLEANS – Use of minimally invasive radical hysterectomy to treat early-stage cervical cancer has grown over the past decade, and in current U.S. practice, roughly half of these cases are done with a minimally-invasive approach, with the rest done by conventional laparotomy. But the first data ever reported from a large, prospective trial that compared the efficacy of both methods for cervical cancer had the unexpected finding that disease-free survival following minimally invasive procedures significantly lagged behind radical hysterectomies done by open laparotomy, Pedro T. Ramirez, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Just after this report came results from a second study that used propensity score–adjusted observational data from the National Cancer Database and found significantly worse overall survival following minimally invasive radical hysterectomy for early-stage cervical cancer, compared with laparotomy, said J. Alejandro Rauh-Hain, MD, a gynecologic oncologist at the University of Texas MD Anderson Cancer Center in Houston.
Both findings were “very surprising,” said Dr. Rauh-Hain in a video interview. “I was pretty sure we’d see no difference” in outcomes between minimally invasive radical hysterectomies and the same surgery either done by laparoscope or robotically assisted.
Prior prospective comparisons of minimally invasive and open surgical methods for other cancer types, including endometrial, gastric, and ovarian, showed no differences in cancer recurrences and survival, which led to widening use of minimally invasive surgery (MIS) for cervical cancer despite no direct evidence supporting equivalence, Dr. Rauh-Hain noted. “We adopted it with no data. It made sense that cervical cancer would be the same as endometrial cancer,” he explained.
The Laparoscopic Approach to Cervical Cancer (LACC) trial ran at 33 centers in 12 countries, including six U.S. centers. The study randomized women during 2008-2017 who had stage 1A1, 1A2, or 1B1 cervical cancer to either MIS or open surgery for a radical hysterectomy. Each participating center had to submit to a trial review committee full case records for 10 patients and unedited surgical videos of two patients who had previously undergone a minimally invasive radical hysterectomy at the center to document local prowess with MIS.
Dr. Ramirez and his colleagues designed LACC to prove the noninferiority of MIS and calculated an expected enrollment of 740 patients based on statistical expectations, but the study stopped early after enrolling 631 patients because of the adverse outcomes identified in the MIS patients, with a median follow-up of 2.5 years instead of the planned follow-up of 4.5 years. The study reached the 4.5-year follow-up in about 39% of patients. Of the 312 patients randomized to undergo laparotomy, 88% actually underwent the surgery; of the 319 patients randomized to MIS, 91% received this surgery, with 16% of the MIS procedures done using robotic assistance.
The study’s primary endpoint was disease-free survival at 4.5 years, which occurred in 86% of the MIS patients and in 96.5% of the laparotomy patients, a difference that failed to meet the study’s prespecified definition of noninferiority for MIS, reported Dr. Ramirez, a professor of gynecologic oncology and director of Minimally Invasive Surgery Research and Education at the MD Anderson Cancer Center. In addition, several secondary analyses of the data all showed starkly superior outcomes in the laparotomy subgroup.
Disease-free survival among all patients regardless of follow-up duration occurred in 98% of laparotomy patients and 92% of MIS patients, which translated into a 3.74 hazard ratio (P = .002) for disease recurrence or death among the MIS patients when compared with laparotomy patients. The all-cause mortality rates were 1% in the laparotomy patients and 6% among the MIS patients, a hazard ratio of 6.00 (P = .004). The risk of local or regional recurrences was more than fourfold higher in the MIS patients. A blinded, central panel adjudicated all recurrences identified during the study.
The LACC results “should be discussed with patients scheduled to undergo radical hysterectomy” for cervical cancer, Dr. Ramirez concluded.
The observational data from the National Cancer Database used in the analysis led by Dr. Rauh-Hain came from 2,221 patients hospitalized and treated with radical hysterectomy and pelvic lymph node dissection at a U.S. center during 2010-2012 for either stage 1A2 or 1B1 cervical cancer. Among these patients, 47.5% underwent MIS, with 79% of those procedures done with robotic assistance, while the other 52.5% underwent open laparotomy, Dr. Rauh-Hain reported. Additional analysis of data from this database by the researchers showed that, although the first report of MIS for radical hysterectomy appeared in 1992, the approach remained largely unused in U.S. practice until 2007, when use of MIS began to sharply rise. By 2010, about a third of radical hysterectomies for cervical cancer involved MIS, and usage increased still further during 2011 and 2012 to produce a nearly 48% rate during the 3-year study period.
The primary endpoint of Dr. Rauh-Hain’s analysis was overall survival following propensity-score matching of the MIS and laparotomy patients using 13 demographic and clinical criteria. The analysis showed 4-year mortality rates of 5.8% among the laparotomy patients and 8.4% among the MIS patients, which calculated to a relatively increased mortality hazard from MIS of 48% (P = .02).
Dr. Rauh-Hain also reported results from an interrupted time series analysis using data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. This analysis compared annual 4-year relative survival rates among women undergoing radical hysterectomy for cervical cancer and found that, after survival rates showed a gradual, steady rise during the years culminating in 2006, once MIS began being more widely used in 2007 survival rates began to drop, with a statistically significant annualized decline of 1% through 2010.
Based on the results from both studies, “at MD Anderson we discuss the results with patients,” with the consequence that the percentage of patients treated with laparotomy is now increasing, Dr. Rauh-Hain said. The results from both studies “are concerning,” he explained.
SOURCE: Ramirez PT and Rauh-Hain JA. SGO 2018, Late-Breaking Abstracts 1 and 2.
REPORTING FROM SGO 2018
Key clinical point: Laparotomy produced better survival than did minimally invasive surgery for cervical cancer.
Major finding: Disease-free survival after 4.5 years was 96.5% with laparotomy and 86.0% with minimally invasive surgery.
Study details: LACC was a multicenter, randomized trial with 631 patients. The observational study included 2,221 patients from the National Cancer Database during 2010-2012.
Disclosures: Dr. Ramirez and Dr. Rauh-Hain had no disclosures.
Source: Ramirez PT and Rauh-Hain JA. SGO 2018, Late-Breaking Abstracts 1 and 2.
Ari Green, MD
VIDEO: Poorer cardiometabolic health seen in men with low sperm count
CHICAGO – Low testosterone levels alone didn’t account for the finding, said Alberto Ferlin, MD, PhD, professor of reproductive endocrinology at the University of Brescia, Italy.
“So at the end, we showed that, independent of testosterone, low sperm count could be a marker of general male health, in particular for cardiovascular risk factors or metabolic derangement,” said Dr. Ferlin in an interview following a press conference at the annual meeting of the Endocrine Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The Italian study, which Dr. Ferlin said was the largest of its kind to date, studied 5,177 males who were part of an infertile couple, comparing men with low sperm count (less than 39 million sperm per ejaculate) with those with normal sperm count (at least 39 million sperm per ejaculate). In all, 2,583 of the participants had low sperm counts.
“Our main aim was to understand if semen analysis and, in general, the reproductive function of a man, could be a marker of his general cardiovascular and metabolic health,” said Dr. Ferlin.
Only men with a comprehensive work-up were included, so all participants had a medical history and physical exam, and semen analysis and culture. Additional components of the evaluation included blood lipid and glucose metabolism testing, reproductive hormone levels, ultrasound of the testes and, for men diagnosed with hypogonadism, bone densitometry.
The study, said Dr. Ferlin, found that among men with a low total sperm count, there was a high prevalence of hypogonadism, defined as both low testosterone and elevated levels of luteinizing hormone. Additionally, these men had a high prevalence of elevated luteinizing hormones with normal testosterone – “so-called subclinical hypogonadism,” said Dr. Ferlin.
In men with a low sperm count – defined as fewer than 39 million sperm per ejaculate – the prevalence of biochemical hypogonadism was about 45%, compared with just 6% in men with normal sperm counts, said Dr. Ferlin. Men with infertility had an odds ratio for hypogonadism of 12.2, said Dr. Ferlin (95% confidence interval, 10.2-14.6).
Additionally, Dr. Ferlin reported that 35% of men with hypogonadism had osteopenia, and 17% met criteria for osteoporosis. The numbers surprised the investigators. “These are very young men – about 30 years old,” said Dr. Ferlin.
Dr. Ferlin and his collaborators also looked at the subset of eugonadal men in the study, comparing those with normal sperm counts (n = 2,431) to those who had low sperm counts, (n = 1,423). They found that men with low sperm counts had significantly higher body mass index, waist circumference, systolic blood pressure, hemoglobin A1c, and homeostatic model assessment of insulin resistance (HOMA-IR) levels (P less than .001 for all).
High density lipoprotein (HDL) cholesterol, testosterone, and follicle stimulating hormone levels were also significantly lower for men with low sperm count. “Men with oligozoospermia … have an increased risk of metabolic derangement – so, altered lipid profile with higher LDL cholesterol and lower HDL [cholesterol], higher triglycerides, higher insulin resistance,” said Dr. Ferlin.
The findings have implications for reproductive endocrinologists caring for couples with infertility, said Dr. Ferlin. “Infertile men should be studied comprehensively, and the diagnosis cannot be limited to just one semen analysis,” given the study’s findings, he said. “All these men should be counseled, should be treated … for worsening of these cardiovascular and metabolic risk factors that are present in such frequency in oligozoospermic men.”
Dr. Ferlin reported no conflicts of interest.
CHICAGO – Low testosterone levels alone didn’t account for the finding, said Alberto Ferlin, MD, PhD, professor of reproductive endocrinology at the University of Brescia, Italy.
“So at the end, we showed that, independent of testosterone, low sperm count could be a marker of general male health, in particular for cardiovascular risk factors or metabolic derangement,” said Dr. Ferlin in an interview following a press conference at the annual meeting of the Endocrine Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The Italian study, which Dr. Ferlin said was the largest of its kind to date, studied 5,177 males who were part of an infertile couple, comparing men with low sperm count (less than 39 million sperm per ejaculate) with those with normal sperm count (at least 39 million sperm per ejaculate). In all, 2,583 of the participants had low sperm counts.
“Our main aim was to understand if semen analysis and, in general, the reproductive function of a man, could be a marker of his general cardiovascular and metabolic health,” said Dr. Ferlin.
Only men with a comprehensive work-up were included, so all participants had a medical history and physical exam, and semen analysis and culture. Additional components of the evaluation included blood lipid and glucose metabolism testing, reproductive hormone levels, ultrasound of the testes and, for men diagnosed with hypogonadism, bone densitometry.
The study, said Dr. Ferlin, found that among men with a low total sperm count, there was a high prevalence of hypogonadism, defined as both low testosterone and elevated levels of luteinizing hormone. Additionally, these men had a high prevalence of elevated luteinizing hormones with normal testosterone – “so-called subclinical hypogonadism,” said Dr. Ferlin.
In men with a low sperm count – defined as fewer than 39 million sperm per ejaculate – the prevalence of biochemical hypogonadism was about 45%, compared with just 6% in men with normal sperm counts, said Dr. Ferlin. Men with infertility had an odds ratio for hypogonadism of 12.2, said Dr. Ferlin (95% confidence interval, 10.2-14.6).
Additionally, Dr. Ferlin reported that 35% of men with hypogonadism had osteopenia, and 17% met criteria for osteoporosis. The numbers surprised the investigators. “These are very young men – about 30 years old,” said Dr. Ferlin.
Dr. Ferlin and his collaborators also looked at the subset of eugonadal men in the study, comparing those with normal sperm counts (n = 2,431) to those who had low sperm counts, (n = 1,423). They found that men with low sperm counts had significantly higher body mass index, waist circumference, systolic blood pressure, hemoglobin A1c, and homeostatic model assessment of insulin resistance (HOMA-IR) levels (P less than .001 for all).
High density lipoprotein (HDL) cholesterol, testosterone, and follicle stimulating hormone levels were also significantly lower for men with low sperm count. “Men with oligozoospermia … have an increased risk of metabolic derangement – so, altered lipid profile with higher LDL cholesterol and lower HDL [cholesterol], higher triglycerides, higher insulin resistance,” said Dr. Ferlin.
The findings have implications for reproductive endocrinologists caring for couples with infertility, said Dr. Ferlin. “Infertile men should be studied comprehensively, and the diagnosis cannot be limited to just one semen analysis,” given the study’s findings, he said. “All these men should be counseled, should be treated … for worsening of these cardiovascular and metabolic risk factors that are present in such frequency in oligozoospermic men.”
Dr. Ferlin reported no conflicts of interest.
CHICAGO – Low testosterone levels alone didn’t account for the finding, said Alberto Ferlin, MD, PhD, professor of reproductive endocrinology at the University of Brescia, Italy.
“So at the end, we showed that, independent of testosterone, low sperm count could be a marker of general male health, in particular for cardiovascular risk factors or metabolic derangement,” said Dr. Ferlin in an interview following a press conference at the annual meeting of the Endocrine Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The Italian study, which Dr. Ferlin said was the largest of its kind to date, studied 5,177 males who were part of an infertile couple, comparing men with low sperm count (less than 39 million sperm per ejaculate) with those with normal sperm count (at least 39 million sperm per ejaculate). In all, 2,583 of the participants had low sperm counts.
“Our main aim was to understand if semen analysis and, in general, the reproductive function of a man, could be a marker of his general cardiovascular and metabolic health,” said Dr. Ferlin.
Only men with a comprehensive work-up were included, so all participants had a medical history and physical exam, and semen analysis and culture. Additional components of the evaluation included blood lipid and glucose metabolism testing, reproductive hormone levels, ultrasound of the testes and, for men diagnosed with hypogonadism, bone densitometry.
The study, said Dr. Ferlin, found that among men with a low total sperm count, there was a high prevalence of hypogonadism, defined as both low testosterone and elevated levels of luteinizing hormone. Additionally, these men had a high prevalence of elevated luteinizing hormones with normal testosterone – “so-called subclinical hypogonadism,” said Dr. Ferlin.
In men with a low sperm count – defined as fewer than 39 million sperm per ejaculate – the prevalence of biochemical hypogonadism was about 45%, compared with just 6% in men with normal sperm counts, said Dr. Ferlin. Men with infertility had an odds ratio for hypogonadism of 12.2, said Dr. Ferlin (95% confidence interval, 10.2-14.6).
Additionally, Dr. Ferlin reported that 35% of men with hypogonadism had osteopenia, and 17% met criteria for osteoporosis. The numbers surprised the investigators. “These are very young men – about 30 years old,” said Dr. Ferlin.
Dr. Ferlin and his collaborators also looked at the subset of eugonadal men in the study, comparing those with normal sperm counts (n = 2,431) to those who had low sperm counts, (n = 1,423). They found that men with low sperm counts had significantly higher body mass index, waist circumference, systolic blood pressure, hemoglobin A1c, and homeostatic model assessment of insulin resistance (HOMA-IR) levels (P less than .001 for all).
High density lipoprotein (HDL) cholesterol, testosterone, and follicle stimulating hormone levels were also significantly lower for men with low sperm count. “Men with oligozoospermia … have an increased risk of metabolic derangement – so, altered lipid profile with higher LDL cholesterol and lower HDL [cholesterol], higher triglycerides, higher insulin resistance,” said Dr. Ferlin.
The findings have implications for reproductive endocrinologists caring for couples with infertility, said Dr. Ferlin. “Infertile men should be studied comprehensively, and the diagnosis cannot be limited to just one semen analysis,” given the study’s findings, he said. “All these men should be counseled, should be treated … for worsening of these cardiovascular and metabolic risk factors that are present in such frequency in oligozoospermic men.”
Dr. Ferlin reported no conflicts of interest.
REPORTING FROM ENDO 2018
Depression and substance abuse
VIDEO: Biomarker accurately predicted primary nonfunction after liver transplant
, researchers reported in Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Glycomic alterations of immunoglobulin G “represent inflammatory disturbances in the liver that [mean it] will fail after transplantation,” wrote Xavier Verhelst, MD, of Ghent (Belgium) University Hospital, and his associates. The new glycomarker “could be a tool to safely select high-risk organs for liver transplantation that otherwise would be discarded from the donor pool based on a conventional clinical assessment,” and also could help prevent engraftment failures. “To our knowledge, not a single biomarker has demonstrated the same accuracy today,” they wrote in the April issue of Gastroenterology.
Chronic shortages of donor livers contribute to morbidity and death worldwide. However, relaxing donor criteria is controversial because of the increased risk of primary nonfunction, which affects some 2%-10% of liver transplantation patients, and early allograft dysfunction, which is even more common. Although no reliable scoring systems or biomarkers have been able to predict these outcomes prior to transplantation, clinical glycomics of serum has proven useful for diagnosing hepatic fibrosis, cirrhosis, and hepatocellular carcinoma, and for distinguishing hepatic steatosis from nonalcoholic steatohepatitis. “Perfusate biomarkers are an attractive alternative [to] liver biopsy or serum markers, because perfusate is believed to represent the condition of the entire liver parenchyma and is easy to collect in large volumes,” the researchers wrote.
Accordingly, they studied 66 patients who underwent liver transplantation at a single center in Belgium and a separate validation cohort of 56 transplantation recipients from two centers. The most common reason for liver transplantation was decompensated cirrhosis secondary to alcoholism, followed by chronic hepatitis C or B virus infection, acute liver failure, and polycystic liver disease. Donor grafts were transported using cold static storage (21° C), and hepatic veins were flushed to collect perfusate before transplantation. Protein-linked N-glycans was isolated from these perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer.
The four patients in the primary study cohort who developed primary nonfunction resembled the others in terms of all clinical and demographic parameters except that they had a markedly increased concentration (P less than .0001) of a single-glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan, dubbed NGA2F. The single patient in the validation cohort who developed primary nonfunction also had a significantly increased concentration of NGA2F (P = .037). There were no false positives in either cohort, and a 13% cutoff for perfusate NGA2F level identified primary nonfunction with 100% accuracy, the researchers said. In a multivariable model of donor risk index and perfusate markers, only NGA2F was prognostic for developing primary nonfunction (P less than .0001).
The researchers found no specific glycomic signature for early allograft dysfunction, perhaps because it is more complex and multifactorial, they wrote. Although electrophoresis testing took 48 hours, work is underway to shorten this to a “clinically acceptable time frame,” they added. They recommended multicenter studies to validate their findings.
Funders included the Research Fund – Flanders and Ghent University. The researchers reported having no conflicts of interest.
SOURCE: Verhelst X et al. Gastroenterology 2018 Jan 6. doi: 10.1053/j.gastro.2017.12.027.
, researchers reported in Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Glycomic alterations of immunoglobulin G “represent inflammatory disturbances in the liver that [mean it] will fail after transplantation,” wrote Xavier Verhelst, MD, of Ghent (Belgium) University Hospital, and his associates. The new glycomarker “could be a tool to safely select high-risk organs for liver transplantation that otherwise would be discarded from the donor pool based on a conventional clinical assessment,” and also could help prevent engraftment failures. “To our knowledge, not a single biomarker has demonstrated the same accuracy today,” they wrote in the April issue of Gastroenterology.
Chronic shortages of donor livers contribute to morbidity and death worldwide. However, relaxing donor criteria is controversial because of the increased risk of primary nonfunction, which affects some 2%-10% of liver transplantation patients, and early allograft dysfunction, which is even more common. Although no reliable scoring systems or biomarkers have been able to predict these outcomes prior to transplantation, clinical glycomics of serum has proven useful for diagnosing hepatic fibrosis, cirrhosis, and hepatocellular carcinoma, and for distinguishing hepatic steatosis from nonalcoholic steatohepatitis. “Perfusate biomarkers are an attractive alternative [to] liver biopsy or serum markers, because perfusate is believed to represent the condition of the entire liver parenchyma and is easy to collect in large volumes,” the researchers wrote.
Accordingly, they studied 66 patients who underwent liver transplantation at a single center in Belgium and a separate validation cohort of 56 transplantation recipients from two centers. The most common reason for liver transplantation was decompensated cirrhosis secondary to alcoholism, followed by chronic hepatitis C or B virus infection, acute liver failure, and polycystic liver disease. Donor grafts were transported using cold static storage (21° C), and hepatic veins were flushed to collect perfusate before transplantation. Protein-linked N-glycans was isolated from these perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer.
The four patients in the primary study cohort who developed primary nonfunction resembled the others in terms of all clinical and demographic parameters except that they had a markedly increased concentration (P less than .0001) of a single-glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan, dubbed NGA2F. The single patient in the validation cohort who developed primary nonfunction also had a significantly increased concentration of NGA2F (P = .037). There were no false positives in either cohort, and a 13% cutoff for perfusate NGA2F level identified primary nonfunction with 100% accuracy, the researchers said. In a multivariable model of donor risk index and perfusate markers, only NGA2F was prognostic for developing primary nonfunction (P less than .0001).
The researchers found no specific glycomic signature for early allograft dysfunction, perhaps because it is more complex and multifactorial, they wrote. Although electrophoresis testing took 48 hours, work is underway to shorten this to a “clinically acceptable time frame,” they added. They recommended multicenter studies to validate their findings.
Funders included the Research Fund – Flanders and Ghent University. The researchers reported having no conflicts of interest.
SOURCE: Verhelst X et al. Gastroenterology 2018 Jan 6. doi: 10.1053/j.gastro.2017.12.027.
, researchers reported in Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Glycomic alterations of immunoglobulin G “represent inflammatory disturbances in the liver that [mean it] will fail after transplantation,” wrote Xavier Verhelst, MD, of Ghent (Belgium) University Hospital, and his associates. The new glycomarker “could be a tool to safely select high-risk organs for liver transplantation that otherwise would be discarded from the donor pool based on a conventional clinical assessment,” and also could help prevent engraftment failures. “To our knowledge, not a single biomarker has demonstrated the same accuracy today,” they wrote in the April issue of Gastroenterology.
Chronic shortages of donor livers contribute to morbidity and death worldwide. However, relaxing donor criteria is controversial because of the increased risk of primary nonfunction, which affects some 2%-10% of liver transplantation patients, and early allograft dysfunction, which is even more common. Although no reliable scoring systems or biomarkers have been able to predict these outcomes prior to transplantation, clinical glycomics of serum has proven useful for diagnosing hepatic fibrosis, cirrhosis, and hepatocellular carcinoma, and for distinguishing hepatic steatosis from nonalcoholic steatohepatitis. “Perfusate biomarkers are an attractive alternative [to] liver biopsy or serum markers, because perfusate is believed to represent the condition of the entire liver parenchyma and is easy to collect in large volumes,” the researchers wrote.
Accordingly, they studied 66 patients who underwent liver transplantation at a single center in Belgium and a separate validation cohort of 56 transplantation recipients from two centers. The most common reason for liver transplantation was decompensated cirrhosis secondary to alcoholism, followed by chronic hepatitis C or B virus infection, acute liver failure, and polycystic liver disease. Donor grafts were transported using cold static storage (21° C), and hepatic veins were flushed to collect perfusate before transplantation. Protein-linked N-glycans was isolated from these perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer.
The four patients in the primary study cohort who developed primary nonfunction resembled the others in terms of all clinical and demographic parameters except that they had a markedly increased concentration (P less than .0001) of a single-glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan, dubbed NGA2F. The single patient in the validation cohort who developed primary nonfunction also had a significantly increased concentration of NGA2F (P = .037). There were no false positives in either cohort, and a 13% cutoff for perfusate NGA2F level identified primary nonfunction with 100% accuracy, the researchers said. In a multivariable model of donor risk index and perfusate markers, only NGA2F was prognostic for developing primary nonfunction (P less than .0001).
The researchers found no specific glycomic signature for early allograft dysfunction, perhaps because it is more complex and multifactorial, they wrote. Although electrophoresis testing took 48 hours, work is underway to shorten this to a “clinically acceptable time frame,” they added. They recommended multicenter studies to validate their findings.
Funders included the Research Fund – Flanders and Ghent University. The researchers reported having no conflicts of interest.
SOURCE: Verhelst X et al. Gastroenterology 2018 Jan 6. doi: 10.1053/j.gastro.2017.12.027.
FROM GASTROENTEROLOGY
Key clinical point: A glycomarker in donor liver perfusate was 100% accurate at predicting primary nonfunction after liver transplantation.
Major finding: In a multivariable model of donor risk index and perfusate markers, only the single-glycan, NGA2F was a significant predictor of primary nonfunction (P less than .0001).
Data source: A dual-center, prospective study of 66 liver transplant patients and a 55-member validation cohort.
Disclosures: Funders included the Research Fund – Flanders and Ghent University. The researchers reported having no conflicts of interest.
Source: Verhelst X et al. Gastroenterology 2018 Jan 6. doi: 10.1053/j.gastro.2017.12.027.
