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Progress in Vascular Disease Treatments: Hype vs. Reality
Today we are witnessing unprecedented rapid development and dissemination of new scientific information regarding vascular diseases, and it is becoming increasingly difficult for busy practitioners to keep up with the avalanche of information, according to Dr. Bruce A. Perler.
To help practitioners differentiate the hype from reality, the “Progress in the Medical Treatments of Vascular Disease; Vascular Diseases and Risk Prediction” session on Friday will bring together internationally respected experts in the field. These faculty will present “the latest and most important advances in the perioperative and long-term medical management of our patients in a succinct and easily digestible fashion,” said Dr. Perler of Johns Hopkins University School of Medicine, who will co-moderate the session with Dr. Caron B. Rockman of New York University School of Medicine.
He added that the information presented in this session will afford the practitioner the latest scientifically proven perioperative and long-term therapy to optimize the patient’s circulatory health.
Further, attendees can take what they learn in this session back to their practice to properly counsel patients about their care – and to answer the questions that patients often bring to the office about these drugs and issues that they hear about in the lay press, he said.
Two critically important talks to be included in the session are: “Which Patients Should Receive Primary Prevention Lipid Lowering Statin Therapy: What Drug and Dose: How Do the HOPE 3 Trial Findings Help,” by Jeffrey S. Berger, MD, associate professor of medicine and surgery, NYU School of Medicine, and “How Do PCSK-9 Inhibitors Work: When and How Should They Currently Be Used: Advantages and Limitations,” by Dr. Natalie A. Marks of the NYU Lutheran Medical Center, he said.
“Hardly a month goes by without yet another article appearing in the lay press about statins. Patients are aware of statins, the associated controversies, and now are hearing about PCSK-9 inhibitors. These talks will inform the vascular surgeon about the key issues with respect to statin therapy and this exciting new alternative,” he said.
Among the nine other informative talks to be presented in the session cover important topics such as ACE inhibitors, angiotensin receptor blockers, the use of cilostazol, and troponin texting.
“Achieving the best results of our vascular surgical procedures requires more than doing the right procedure on the right patient at the right time,” Dr. Perler said. “It also requires managing the patient’s medical and perioperative care compulsively. Keeping abreast of the latest developments, highlighted in this session, will not only optimize your patients’ care, but provide a competitive practice advantage for the contemporary vascular surgeon.”
Today we are witnessing unprecedented rapid development and dissemination of new scientific information regarding vascular diseases, and it is becoming increasingly difficult for busy practitioners to keep up with the avalanche of information, according to Dr. Bruce A. Perler.
To help practitioners differentiate the hype from reality, the “Progress in the Medical Treatments of Vascular Disease; Vascular Diseases and Risk Prediction” session on Friday will bring together internationally respected experts in the field. These faculty will present “the latest and most important advances in the perioperative and long-term medical management of our patients in a succinct and easily digestible fashion,” said Dr. Perler of Johns Hopkins University School of Medicine, who will co-moderate the session with Dr. Caron B. Rockman of New York University School of Medicine.
He added that the information presented in this session will afford the practitioner the latest scientifically proven perioperative and long-term therapy to optimize the patient’s circulatory health.
Further, attendees can take what they learn in this session back to their practice to properly counsel patients about their care – and to answer the questions that patients often bring to the office about these drugs and issues that they hear about in the lay press, he said.
Two critically important talks to be included in the session are: “Which Patients Should Receive Primary Prevention Lipid Lowering Statin Therapy: What Drug and Dose: How Do the HOPE 3 Trial Findings Help,” by Jeffrey S. Berger, MD, associate professor of medicine and surgery, NYU School of Medicine, and “How Do PCSK-9 Inhibitors Work: When and How Should They Currently Be Used: Advantages and Limitations,” by Dr. Natalie A. Marks of the NYU Lutheran Medical Center, he said.
“Hardly a month goes by without yet another article appearing in the lay press about statins. Patients are aware of statins, the associated controversies, and now are hearing about PCSK-9 inhibitors. These talks will inform the vascular surgeon about the key issues with respect to statin therapy and this exciting new alternative,” he said.
Among the nine other informative talks to be presented in the session cover important topics such as ACE inhibitors, angiotensin receptor blockers, the use of cilostazol, and troponin texting.
“Achieving the best results of our vascular surgical procedures requires more than doing the right procedure on the right patient at the right time,” Dr. Perler said. “It also requires managing the patient’s medical and perioperative care compulsively. Keeping abreast of the latest developments, highlighted in this session, will not only optimize your patients’ care, but provide a competitive practice advantage for the contemporary vascular surgeon.”
Today we are witnessing unprecedented rapid development and dissemination of new scientific information regarding vascular diseases, and it is becoming increasingly difficult for busy practitioners to keep up with the avalanche of information, according to Dr. Bruce A. Perler.
To help practitioners differentiate the hype from reality, the “Progress in the Medical Treatments of Vascular Disease; Vascular Diseases and Risk Prediction” session on Friday will bring together internationally respected experts in the field. These faculty will present “the latest and most important advances in the perioperative and long-term medical management of our patients in a succinct and easily digestible fashion,” said Dr. Perler of Johns Hopkins University School of Medicine, who will co-moderate the session with Dr. Caron B. Rockman of New York University School of Medicine.
He added that the information presented in this session will afford the practitioner the latest scientifically proven perioperative and long-term therapy to optimize the patient’s circulatory health.
Further, attendees can take what they learn in this session back to their practice to properly counsel patients about their care – and to answer the questions that patients often bring to the office about these drugs and issues that they hear about in the lay press, he said.
Two critically important talks to be included in the session are: “Which Patients Should Receive Primary Prevention Lipid Lowering Statin Therapy: What Drug and Dose: How Do the HOPE 3 Trial Findings Help,” by Jeffrey S. Berger, MD, associate professor of medicine and surgery, NYU School of Medicine, and “How Do PCSK-9 Inhibitors Work: When and How Should They Currently Be Used: Advantages and Limitations,” by Dr. Natalie A. Marks of the NYU Lutheran Medical Center, he said.
“Hardly a month goes by without yet another article appearing in the lay press about statins. Patients are aware of statins, the associated controversies, and now are hearing about PCSK-9 inhibitors. These talks will inform the vascular surgeon about the key issues with respect to statin therapy and this exciting new alternative,” he said.
Among the nine other informative talks to be presented in the session cover important topics such as ACE inhibitors, angiotensin receptor blockers, the use of cilostazol, and troponin texting.
“Achieving the best results of our vascular surgical procedures requires more than doing the right procedure on the right patient at the right time,” Dr. Perler said. “It also requires managing the patient’s medical and perioperative care compulsively. Keeping abreast of the latest developments, highlighted in this session, will not only optimize your patients’ care, but provide a competitive practice advantage for the contemporary vascular surgeon.”
Masitinib May Provide Clinical Benefits for Patients with ALS
SAN DIEGO—Masitinib may provide meaningful clinical benefits for patients with amyotrophic lateral sclerosis (ALS), according to research presented at the 142nd Annual Meeting of the American Neurological Association. Early initiation of masitinib may be more beneficial than delayed initiation.
The worldwide prevalence of ALS is approximately 235,000. By 2040, the prevalence is expected to increase by 69%. Riluzole, the only widely available drug for the treatment of ALS, has been associated with little improvement in quality of life and modest increase in survival. IV edaravone demonstrated efficacy only in patients in good clinical condition, which is estimated to be less than 7% of patients with ALS.
Masitinib, an oral tyrosine kinase inhibitor with activity against CSF1/CSF1R signaling and mast cell function, is under investigation as a therapeutic option for patients with ALS. Masitinib provides neuroprotection in the CNS and peripheral nervous system by targeting microglia and macrophage and mast cell activity. The drug has been associated with significantly slower progression of paralysis in post paralytic rats. To test this therapy in patients with ALS, Angela Genge, MD, Director of the ALS Clinic at the Montreal Neurological Institute and Hospital, and colleagues conducted a double blind, placebo-controlled, randomized trial. 
A total of 394 people from nine countries were included in the study. Patients with ALS were randomized to riluzole (100 mg/kg) plus either 4.5 mg/kg/day of oral masitinib, 3.0 mg/kg/day of oral masitinib, or placebo over 48 weeks.
The primary end point was absolute change in ALS Functional Rating Scale-Revised (ALSFRS-R) at 48 weeks in patients with baseline ALSFRS-R progression of less than 1.1 points per month. Secondary end points included the 40-item ALS Assessment Questionnaire (ALSAQ-40), forced vital capacity, and survival to event (defined as ALSFRS-R deterioration of 9 points from baseline or death). Researchers categorized participants as normal progressors (ie, those with a rate of change in ALSFRS-R score < 1.1 points per month) or faster progressors (ie, those with a rate of change in ALSFRS-R score ≥ 1.1 points per month).
Masitinib showed significant benefit over placebo in ALSFRS-R. At week 48, the score had decreased by 12.6 points among controls, compared with 9.2 points in the masitinib groups. Masitinib was associated with 27% slowing of ALSFRS-R deterioration, 29% slowing of deterioration in quality of life, 22% slowing of deterioration in respiratory function, and 25% delay in disease progression.
Secondary analyses also indicated masitinib’s superiority to placebo. A post hoc analysis indicated that early treatment (ie, at less than 24 months duration of illness) conferred greater benefits than delayed treatment. Patients who had milder symptoms or shorter duration of illness showed enhanced masitinib treatment effect.Adverse events with greatest positive difference between masitinib and placebo treatment arms were maculopapular rash and peripheral edema. The rate of adverse events was 78.9% for placebo, 88.4% for the 4.5-mg/kg/day dose of masitinib, and 84.7% for the 3.0-mg/kg/day dose of masitinib. No deaths related to study treatment were reported in either masitinib or placebo groups.
—Erica Tricarico
SAN DIEGO—Masitinib may provide meaningful clinical benefits for patients with amyotrophic lateral sclerosis (ALS), according to research presented at the 142nd Annual Meeting of the American Neurological Association. Early initiation of masitinib may be more beneficial than delayed initiation.
The worldwide prevalence of ALS is approximately 235,000. By 2040, the prevalence is expected to increase by 69%. Riluzole, the only widely available drug for the treatment of ALS, has been associated with little improvement in quality of life and modest increase in survival. IV edaravone demonstrated efficacy only in patients in good clinical condition, which is estimated to be less than 7% of patients with ALS.
Masitinib, an oral tyrosine kinase inhibitor with activity against CSF1/CSF1R signaling and mast cell function, is under investigation as a therapeutic option for patients with ALS. Masitinib provides neuroprotection in the CNS and peripheral nervous system by targeting microglia and macrophage and mast cell activity. The drug has been associated with significantly slower progression of paralysis in post paralytic rats. To test this therapy in patients with ALS, Angela Genge, MD, Director of the ALS Clinic at the Montreal Neurological Institute and Hospital, and colleagues conducted a double blind, placebo-controlled, randomized trial.
A total of 394 people from nine countries were included in the study. Patients with ALS were randomized to riluzole (100 mg/kg) plus either 4.5 mg/kg/day of oral masitinib, 3.0 mg/kg/day of oral masitinib, or placebo over 48 weeks.
The primary end point was absolute change in ALS Functional Rating Scale-Revised (ALSFRS-R) at 48 weeks in patients with baseline ALSFRS-R progression of less than 1.1 points per month. Secondary end points included the 40-item ALS Assessment Questionnaire (ALSAQ-40), forced vital capacity, and survival to event (defined as ALSFRS-R deterioration of 9 points from baseline or death). Researchers categorized participants as normal progressors (ie, those with a rate of change in ALSFRS-R score < 1.1 points per month) or faster progressors (ie, those with a rate of change in ALSFRS-R score ≥ 1.1 points per month).
Masitinib showed significant benefit over placebo in ALSFRS-R. At week 48, the score had decreased by 12.6 points among controls, compared with 9.2 points in the masitinib groups. Masitinib was associated with 27% slowing of ALSFRS-R deterioration, 29% slowing of deterioration in quality of life, 22% slowing of deterioration in respiratory function, and 25% delay in disease progression.
Secondary analyses also indicated masitinib’s superiority to placebo. A post hoc analysis indicated that early treatment (ie, at less than 24 months duration of illness) conferred greater benefits than delayed treatment. Patients who had milder symptoms or shorter duration of illness showed enhanced masitinib treatment effect.Adverse events with greatest positive difference between masitinib and placebo treatment arms were maculopapular rash and peripheral edema. The rate of adverse events was 78.9% for placebo, 88.4% for the 4.5-mg/kg/day dose of masitinib, and 84.7% for the 3.0-mg/kg/day dose of masitinib. No deaths related to study treatment were reported in either masitinib or placebo groups.
—Erica Tricarico
SAN DIEGO—Masitinib may provide meaningful clinical benefits for patients with amyotrophic lateral sclerosis (ALS), according to research presented at the 142nd Annual Meeting of the American Neurological Association. Early initiation of masitinib may be more beneficial than delayed initiation.
The worldwide prevalence of ALS is approximately 235,000. By 2040, the prevalence is expected to increase by 69%. Riluzole, the only widely available drug for the treatment of ALS, has been associated with little improvement in quality of life and modest increase in survival. IV edaravone demonstrated efficacy only in patients in good clinical condition, which is estimated to be less than 7% of patients with ALS.
Masitinib, an oral tyrosine kinase inhibitor with activity against CSF1/CSF1R signaling and mast cell function, is under investigation as a therapeutic option for patients with ALS. Masitinib provides neuroprotection in the CNS and peripheral nervous system by targeting microglia and macrophage and mast cell activity. The drug has been associated with significantly slower progression of paralysis in post paralytic rats. To test this therapy in patients with ALS, Angela Genge, MD, Director of the ALS Clinic at the Montreal Neurological Institute and Hospital, and colleagues conducted a double blind, placebo-controlled, randomized trial.
A total of 394 people from nine countries were included in the study. Patients with ALS were randomized to riluzole (100 mg/kg) plus either 4.5 mg/kg/day of oral masitinib, 3.0 mg/kg/day of oral masitinib, or placebo over 48 weeks.
The primary end point was absolute change in ALS Functional Rating Scale-Revised (ALSFRS-R) at 48 weeks in patients with baseline ALSFRS-R progression of less than 1.1 points per month. Secondary end points included the 40-item ALS Assessment Questionnaire (ALSAQ-40), forced vital capacity, and survival to event (defined as ALSFRS-R deterioration of 9 points from baseline or death). Researchers categorized participants as normal progressors (ie, those with a rate of change in ALSFRS-R score < 1.1 points per month) or faster progressors (ie, those with a rate of change in ALSFRS-R score ≥ 1.1 points per month).
Masitinib showed significant benefit over placebo in ALSFRS-R. At week 48, the score had decreased by 12.6 points among controls, compared with 9.2 points in the masitinib groups. Masitinib was associated with 27% slowing of ALSFRS-R deterioration, 29% slowing of deterioration in quality of life, 22% slowing of deterioration in respiratory function, and 25% delay in disease progression.
Secondary analyses also indicated masitinib’s superiority to placebo. A post hoc analysis indicated that early treatment (ie, at less than 24 months duration of illness) conferred greater benefits than delayed treatment. Patients who had milder symptoms or shorter duration of illness showed enhanced masitinib treatment effect.Adverse events with greatest positive difference between masitinib and placebo treatment arms were maculopapular rash and peripheral edema. The rate of adverse events was 78.9% for placebo, 88.4% for the 4.5-mg/kg/day dose of masitinib, and 84.7% for the 3.0-mg/kg/day dose of masitinib. No deaths related to study treatment were reported in either masitinib or placebo groups.
—Erica Tricarico
Injectable agent found to improve knee function in OA patients
SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.
“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”
The study consisted of two parts. In Part A, four dose cohorts ranging from 20 mg to 200 mg per injection were enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and the 200-mg dose was selected dose for Part B of the study.
The median age of the 118 patients was 60 years and their median body mass index was 29.2 kg/m2. No drug-related serious adverse events and no dose-limiting toxicities occurred across doses ranging from 20 mg to 200 mg per injection. The incidence of common adverse events such as knee pain was similar between placebo- and TPX-100-treated knees.
Quantitative MRI showed no measurable between-knee differences in cartilage thickness or volume at 6 or 12 months. However, statistically significant and clinically meaningful differences in knee function were observed in favor of TPX-100-treated knees, compared with controls, including KOOS activities of daily living (P = .008 at 6 and 12 months), KOOS knee-related quality of life (P = .21 at 6 months and P = .03 at 12 months), and a significant reduction in pain going up or down stairs (P = .004 at 12 months). Subjects’ use of nonsteroidal anti-inflammatory medications declined by 63% during the study.
“In this study, we see some terrific, long-term results in knee-related core activities, which certainly were disease modifying from the patients’ perspective,” said Dr. McGuire, who noted that a phase 3 study is being planned. “In addition, patient’s pain going up and down stairs improved significantly, with a marked reduction in analgesic use. Any of us who are experienced in these tough areas of medicine know that early results can look extremely promising, but we have to do larger confirmatory studies.”
SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.
“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”
The study consisted of two parts. In Part A, four dose cohorts ranging from 20 mg to 200 mg per injection were enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and the 200-mg dose was selected dose for Part B of the study.
The median age of the 118 patients was 60 years and their median body mass index was 29.2 kg/m2. No drug-related serious adverse events and no dose-limiting toxicities occurred across doses ranging from 20 mg to 200 mg per injection. The incidence of common adverse events such as knee pain was similar between placebo- and TPX-100-treated knees.
Quantitative MRI showed no measurable between-knee differences in cartilage thickness or volume at 6 or 12 months. However, statistically significant and clinically meaningful differences in knee function were observed in favor of TPX-100-treated knees, compared with controls, including KOOS activities of daily living (P = .008 at 6 and 12 months), KOOS knee-related quality of life (P = .21 at 6 months and P = .03 at 12 months), and a significant reduction in pain going up or down stairs (P = .004 at 12 months). Subjects’ use of nonsteroidal anti-inflammatory medications declined by 63% during the study.
“In this study, we see some terrific, long-term results in knee-related core activities, which certainly were disease modifying from the patients’ perspective,” said Dr. McGuire, who noted that a phase 3 study is being planned. “In addition, patient’s pain going up and down stairs improved significantly, with a marked reduction in analgesic use. Any of us who are experienced in these tough areas of medicine know that early results can look extremely promising, but we have to do larger confirmatory studies.”
SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.
“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”
The study consisted of two parts. In Part A, four dose cohorts ranging from 20 mg to 200 mg per injection were enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and the 200-mg dose was selected dose for Part B of the study.
The median age of the 118 patients was 60 years and their median body mass index was 29.2 kg/m2. No drug-related serious adverse events and no dose-limiting toxicities occurred across doses ranging from 20 mg to 200 mg per injection. The incidence of common adverse events such as knee pain was similar between placebo- and TPX-100-treated knees.
Quantitative MRI showed no measurable between-knee differences in cartilage thickness or volume at 6 or 12 months. However, statistically significant and clinically meaningful differences in knee function were observed in favor of TPX-100-treated knees, compared with controls, including KOOS activities of daily living (P = .008 at 6 and 12 months), KOOS knee-related quality of life (P = .21 at 6 months and P = .03 at 12 months), and a significant reduction in pain going up or down stairs (P = .004 at 12 months). Subjects’ use of nonsteroidal anti-inflammatory medications declined by 63% during the study.
“In this study, we see some terrific, long-term results in knee-related core activities, which certainly were disease modifying from the patients’ perspective,” said Dr. McGuire, who noted that a phase 3 study is being planned. “In addition, patient’s pain going up and down stairs improved significantly, with a marked reduction in analgesic use. Any of us who are experienced in these tough areas of medicine know that early results can look extremely promising, but we have to do larger confirmatory studies.”
AT ACR 2017
Key clinical point:
Major finding: Statistically significant differences in knee function were observed in favor of TPX-100-treated knees, compared with controls, using Knee Injury and Osteoarthritis Outcome Score activities of daily living (P = .008 at 6 and 12 months) and a significant reduction in pain going up or down stairs (P = .004 at 12 months).
Study details: A randomized, proof-of-concept study involving 118 patients with patellofemoral knee OA.
Disclosures: OrthoTrophix sponsored the study. Dr. McGuire is chief medical officer and a cofounder of the company.
Evolution in Management and Treatment of Carotid Artery Disease
“There is a ‘one size fits all’ strategy by a lot of people who simply read a paper or a guideline and say that’s how patients must be treated,” said co-moderator Dr. Ross Naylor, professor of vascular surgery at the University of Leicester and a consultant vascular surgeon at the Leicester Royal Infirmary. “This session will question how you actually treat your patients, so I think it will open people’s eyes toward the benefits of modern medical therapy. It also questions the role of carotid stenting in asymptomatic patients and how to reduce the risks; unless we reduce the risks, it’s going to be less likely to be adopted.”
The session has several themes, he explained. One is the benefit of optimizing best medical therapy: “There are a couple of papers on the role of starting statins before carotid surgery or carotid stenting. There’s now good evidence that if you do this, you will reduce the perioperative risk of stroke, and this needs to be emphasized more in guidelines.”
In addition, Dr. Naylor said, there is increasing evidence that patients who have asymptomatic carotid stenosis, and who are started on good quality medical therapy, have much lower annual risks of stroke than they would 15 to 20 years ago. Presentations by Dr. J. David Spence of Western University and University Hospital in London, Canada, and by Dr. Henrik Sillesen of the University of Copenhagen and Rigshospitalet, will question current attitudes toward intervening in asymptomatic patients. “Their big plea is that the majority can be treated medically,” Dr. Naylor said. “Only a small proportion actually will benefit from stenting and surgery.” Dr. Spence will address the value of Mediterranean and Nordic diets in patients with carotid stenosis, while Dr. Sillesen will examine if stenosis or plaque progression are reasons to treat asymptomatic patients with carotid artery stenting (CAS) versus carotid artery endarterectomy (CEA).
Another theme is looking at efforts to reduce perioperative stroke rates after carotid stenting, Dr. Naylor said: “One of the repeated findings is that the death and stroke rates are lower following carotid surgery rather than carotid stenting. Registries suggest that in a large number of series, stroke rates actually exceed the accepted risks for treating patients with asymptomatic disease, which is 3%, or for symptomatic disease, which is 6%.”
Dr. William A. Gray of Jefferson Medical College and Main Line Health will discuss technical strategies that might be used to reduce perioperative stroke rates, including new techniques and devices such as the double-filter Paladin device. Dr. L. Nelson Hopkins, SUNY Distinguished Professor of Neurosurgery and Radiology, University at Buffalo, will discuss how strokes after CAS and other interventional procedures have greater cognitive deficits than previously thought, even with full neurological recovery.
The discussions will conclude with a presentation by Dr. Mark H. Wholey of the University of Pittsburgh Medical Center, Shady Side, on the etiology, diagnosis and treatment of vertebral artery dissections. “It is so vanishingly rare that we are asked to treat this that almost nobody has any experience,” Dr. Naylor said. “I suspect this will be quite an interesting talk for the audience.”
Co-moderators for the session will be Dr. James May, Emeritus Bosch Professor of Surgery and associated dean of surgical sciences at the University of Sydney, and a vascular surgeon at Royal Prince Alfred Hospital; Dr. Wesley S. Moore, professor and chief emeritus of vascular surgery at UCLA Medical Center; and Dr. Enrico Ascher, chief of vascular surgery at NYU Hospitals, and professor of surgery at New York University.
“There is a ‘one size fits all’ strategy by a lot of people who simply read a paper or a guideline and say that’s how patients must be treated,” said co-moderator Dr. Ross Naylor, professor of vascular surgery at the University of Leicester and a consultant vascular surgeon at the Leicester Royal Infirmary. “This session will question how you actually treat your patients, so I think it will open people’s eyes toward the benefits of modern medical therapy. It also questions the role of carotid stenting in asymptomatic patients and how to reduce the risks; unless we reduce the risks, it’s going to be less likely to be adopted.”
The session has several themes, he explained. One is the benefit of optimizing best medical therapy: “There are a couple of papers on the role of starting statins before carotid surgery or carotid stenting. There’s now good evidence that if you do this, you will reduce the perioperative risk of stroke, and this needs to be emphasized more in guidelines.”
In addition, Dr. Naylor said, there is increasing evidence that patients who have asymptomatic carotid stenosis, and who are started on good quality medical therapy, have much lower annual risks of stroke than they would 15 to 20 years ago. Presentations by Dr. J. David Spence of Western University and University Hospital in London, Canada, and by Dr. Henrik Sillesen of the University of Copenhagen and Rigshospitalet, will question current attitudes toward intervening in asymptomatic patients. “Their big plea is that the majority can be treated medically,” Dr. Naylor said. “Only a small proportion actually will benefit from stenting and surgery.” Dr. Spence will address the value of Mediterranean and Nordic diets in patients with carotid stenosis, while Dr. Sillesen will examine if stenosis or plaque progression are reasons to treat asymptomatic patients with carotid artery stenting (CAS) versus carotid artery endarterectomy (CEA).
Another theme is looking at efforts to reduce perioperative stroke rates after carotid stenting, Dr. Naylor said: “One of the repeated findings is that the death and stroke rates are lower following carotid surgery rather than carotid stenting. Registries suggest that in a large number of series, stroke rates actually exceed the accepted risks for treating patients with asymptomatic disease, which is 3%, or for symptomatic disease, which is 6%.”
Dr. William A. Gray of Jefferson Medical College and Main Line Health will discuss technical strategies that might be used to reduce perioperative stroke rates, including new techniques and devices such as the double-filter Paladin device. Dr. L. Nelson Hopkins, SUNY Distinguished Professor of Neurosurgery and Radiology, University at Buffalo, will discuss how strokes after CAS and other interventional procedures have greater cognitive deficits than previously thought, even with full neurological recovery.
The discussions will conclude with a presentation by Dr. Mark H. Wholey of the University of Pittsburgh Medical Center, Shady Side, on the etiology, diagnosis and treatment of vertebral artery dissections. “It is so vanishingly rare that we are asked to treat this that almost nobody has any experience,” Dr. Naylor said. “I suspect this will be quite an interesting talk for the audience.”
Co-moderators for the session will be Dr. James May, Emeritus Bosch Professor of Surgery and associated dean of surgical sciences at the University of Sydney, and a vascular surgeon at Royal Prince Alfred Hospital; Dr. Wesley S. Moore, professor and chief emeritus of vascular surgery at UCLA Medical Center; and Dr. Enrico Ascher, chief of vascular surgery at NYU Hospitals, and professor of surgery at New York University.
“There is a ‘one size fits all’ strategy by a lot of people who simply read a paper or a guideline and say that’s how patients must be treated,” said co-moderator Dr. Ross Naylor, professor of vascular surgery at the University of Leicester and a consultant vascular surgeon at the Leicester Royal Infirmary. “This session will question how you actually treat your patients, so I think it will open people’s eyes toward the benefits of modern medical therapy. It also questions the role of carotid stenting in asymptomatic patients and how to reduce the risks; unless we reduce the risks, it’s going to be less likely to be adopted.”
The session has several themes, he explained. One is the benefit of optimizing best medical therapy: “There are a couple of papers on the role of starting statins before carotid surgery or carotid stenting. There’s now good evidence that if you do this, you will reduce the perioperative risk of stroke, and this needs to be emphasized more in guidelines.”
In addition, Dr. Naylor said, there is increasing evidence that patients who have asymptomatic carotid stenosis, and who are started on good quality medical therapy, have much lower annual risks of stroke than they would 15 to 20 years ago. Presentations by Dr. J. David Spence of Western University and University Hospital in London, Canada, and by Dr. Henrik Sillesen of the University of Copenhagen and Rigshospitalet, will question current attitudes toward intervening in asymptomatic patients. “Their big plea is that the majority can be treated medically,” Dr. Naylor said. “Only a small proportion actually will benefit from stenting and surgery.” Dr. Spence will address the value of Mediterranean and Nordic diets in patients with carotid stenosis, while Dr. Sillesen will examine if stenosis or plaque progression are reasons to treat asymptomatic patients with carotid artery stenting (CAS) versus carotid artery endarterectomy (CEA).
Another theme is looking at efforts to reduce perioperative stroke rates after carotid stenting, Dr. Naylor said: “One of the repeated findings is that the death and stroke rates are lower following carotid surgery rather than carotid stenting. Registries suggest that in a large number of series, stroke rates actually exceed the accepted risks for treating patients with asymptomatic disease, which is 3%, or for symptomatic disease, which is 6%.”
Dr. William A. Gray of Jefferson Medical College and Main Line Health will discuss technical strategies that might be used to reduce perioperative stroke rates, including new techniques and devices such as the double-filter Paladin device. Dr. L. Nelson Hopkins, SUNY Distinguished Professor of Neurosurgery and Radiology, University at Buffalo, will discuss how strokes after CAS and other interventional procedures have greater cognitive deficits than previously thought, even with full neurological recovery.
The discussions will conclude with a presentation by Dr. Mark H. Wholey of the University of Pittsburgh Medical Center, Shady Side, on the etiology, diagnosis and treatment of vertebral artery dissections. “It is so vanishingly rare that we are asked to treat this that almost nobody has any experience,” Dr. Naylor said. “I suspect this will be quite an interesting talk for the audience.”
Co-moderators for the session will be Dr. James May, Emeritus Bosch Professor of Surgery and associated dean of surgical sciences at the University of Sydney, and a vascular surgeon at Royal Prince Alfred Hospital; Dr. Wesley S. Moore, professor and chief emeritus of vascular surgery at UCLA Medical Center; and Dr. Enrico Ascher, chief of vascular surgery at NYU Hospitals, and professor of surgery at New York University.
ACA repeal could mean financial ruin for many MI, stroke patients
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: The median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects.
Data source: Modeling study using the National Impatient Sample, U.S. Census data, and U.S. Bureau of Labor Statistics data.
Disclosures: The work was funded by the National Institutes of Health. The lead investigator didn’t have any disclosures.
Gut bacteria influenced response to checkpoint inhibitors
The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.
In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.
“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.
When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).
They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.
To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.
The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.
The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.
“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.
“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
Bacteria also affect epithelial cancers
In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).
Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.
As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,
“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.
They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,
“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.
The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.
The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.
In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.
“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.
When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).
They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.
To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.
The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.
The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.
“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.
“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
Bacteria also affect epithelial cancers
In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).
Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.
As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,
“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.
They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,
“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.
The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.
The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.
In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.
“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.
When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).
They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.
To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.
The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.
The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.
“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.
“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
Bacteria also affect epithelial cancers
In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).
Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.
As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,
“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.
They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,
“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.
The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.
FROM SCIENCE
Key clinical point: Modulating the gut microbome may improve responses to immune checkpoint inhibitors in patients with advanced melanoma, non–small cell lung cancer, and urothelial carcinoma.
Major finding: Responders to a checkpoint inhibitor had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01).
Data source: A series of studies using microbiome samples from cancer patients receiving immune checkpoint inhibitors.
Disclosures: The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots Program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his colleagues was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.
VIDEO: New vaccines target global infections
LAS VEGAS – There are now vaccines for two infectious diseases that “are not purely dermatologic, but have a great impact on many patients around the world,” Kenneth J. Tomecki, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
The recent development of a vaccine to protect against malaria, with an efficacy around 40%, “is something we should all be proud of,” said Dr. Tomecki of the Cleveland Clinic. Another advance is that there is now also a vaccine for Ebola that is so effective, it is being stockpiled in African countries in preparation for future Ebola outbreaks, he added.
Dr. Tomecki had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – There are now vaccines for two infectious diseases that “are not purely dermatologic, but have a great impact on many patients around the world,” Kenneth J. Tomecki, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
The recent development of a vaccine to protect against malaria, with an efficacy around 40%, “is something we should all be proud of,” said Dr. Tomecki of the Cleveland Clinic. Another advance is that there is now also a vaccine for Ebola that is so effective, it is being stockpiled in African countries in preparation for future Ebola outbreaks, he added.
Dr. Tomecki had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – There are now vaccines for two infectious diseases that “are not purely dermatologic, but have a great impact on many patients around the world,” Kenneth J. Tomecki, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
The recent development of a vaccine to protect against malaria, with an efficacy around 40%, “is something we should all be proud of,” said Dr. Tomecki of the Cleveland Clinic. Another advance is that there is now also a vaccine for Ebola that is so effective, it is being stockpiled in African countries in preparation for future Ebola outbreaks, he added.
Dr. Tomecki had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF LAS VEGAS DERMATOLOGY SEMINAR
Stem cells spark successful skin regeneration
Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.
Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.
The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.
“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.
For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.
The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.
“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.
The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.
Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.
Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.
The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.
“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.
For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.
The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.
“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.
The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.
Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.
Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.
The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.
“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.
For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.
The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.
“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.
The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.
FROM NATURE
VIDEO: Consider combining treatments when body sculpting
LAS VEGAS – Currently, there are available treatments that are effective in contouring the body, Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Some devices can help patients looking for reductions of trouble spots, such as around the abdomen, and are safe and effective, said Dr. Zachary of the University of California, Irvine. However, they are not a realistic option for obese or overweight patients, he added.
In addition, other treatments can be combined with body sculpting devices to optimize results, particularly when removing fat in the submental area, he noted.
Dr. Zachary disclosed relationships with Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – Currently, there are available treatments that are effective in contouring the body, Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Some devices can help patients looking for reductions of trouble spots, such as around the abdomen, and are safe and effective, said Dr. Zachary of the University of California, Irvine. However, they are not a realistic option for obese or overweight patients, he added.
In addition, other treatments can be combined with body sculpting devices to optimize results, particularly when removing fat in the submental area, he noted.
Dr. Zachary disclosed relationships with Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – Currently, there are available treatments that are effective in contouring the body, Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Some devices can help patients looking for reductions of trouble spots, such as around the abdomen, and are safe and effective, said Dr. Zachary of the University of California, Irvine. However, they are not a realistic option for obese or overweight patients, he added.
In addition, other treatments can be combined with body sculpting devices to optimize results, particularly when removing fat in the submental area, he noted.
Dr. Zachary disclosed relationships with Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
AT SDEF LAS VEGAS DERMATOLOGY SEMINAR
VIDEO: Hone aesthetic technique with upper face first
LAS VEGAS – For those starting to use toxins and fillers, “my first advice is to get a good education,” Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“Know … how to evaluate your patient, know where the problems are, know what the danger zones are, understand your anatomy,” advised Dr. Zachary of the University of California, Irvine.
, he noted. Procedures on the upper face, such as the treatment for crow’s feet or a brow lift, can be “a home run,” while the lower face is much more complicated, he said in the video interview.
Dr. Zachary disclosed relationships with companies including Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – For those starting to use toxins and fillers, “my first advice is to get a good education,” Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“Know … how to evaluate your patient, know where the problems are, know what the danger zones are, understand your anatomy,” advised Dr. Zachary of the University of California, Irvine.
, he noted. Procedures on the upper face, such as the treatment for crow’s feet or a brow lift, can be “a home run,” while the lower face is much more complicated, he said in the video interview.
Dr. Zachary disclosed relationships with companies including Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – For those starting to use toxins and fillers, “my first advice is to get a good education,” Christopher B. Zachary, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“Know … how to evaluate your patient, know where the problems are, know what the danger zones are, understand your anatomy,” advised Dr. Zachary of the University of California, Irvine.
, he noted. Procedures on the upper face, such as the treatment for crow’s feet or a brow lift, can be “a home run,” while the lower face is much more complicated, he said in the video interview.
Dr. Zachary disclosed relationships with companies including Solta, Zeltiq, Sciton, DUSA, Zimmer, Cutera, Alma, and Amway.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF LAS VEGAS DERMATOLOGY SEMINAR