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Developing machines that detect disease
Smells – of skin, breath, or bodily fluids – can, in some cases, reveal the presence of disease. This fact has led researchers to try to build an odor sensor that could make a fast, reliable diagnosis, and now the field may be on the verge of a breakthrough, according to a recent article in the New York Times.
In addition to various efforts in Austria, Switzerland, and Japan, an English manufacturer – Owlstone Medical – has been making headway with an odor analysis technology. It will be part of a National Health Service trial that will test the sensor for diagnosing lung cancer. The company also is conducting a trial using urine samples to detect colon cancer; its program allows changing the software to change what disease you detect.
Meanwhile, an Israeli chemical engineer, Hossam Haick, is using similar technology, with molecular receptors that have an affinity for certain biomarkers of disease found in the breath. Artificial intelligence allows the sensors to improve with each use, and a paper published last year showed that this system could distinguish among 17 different diseases with up to 86% accuracy.
And in the United States, researchers from the Monell Chemical Senses Center and the University of Pennsylvania are working on an odor sensor that detects ovarian cancer in samples of blood plasma. They chose plasma because it is less likely than breath or urine to be affected by other factors such as diet or environmental chemicals.
These technologies could be available to doctors in 3-5 years, experts say.
Reference
Murphy K. One Day, a Machine Will Smell Whether You’re Sick . New York Times. May 1, 2017. Accessed May 29, 2017.
Smells – of skin, breath, or bodily fluids – can, in some cases, reveal the presence of disease. This fact has led researchers to try to build an odor sensor that could make a fast, reliable diagnosis, and now the field may be on the verge of a breakthrough, according to a recent article in the New York Times.
In addition to various efforts in Austria, Switzerland, and Japan, an English manufacturer – Owlstone Medical – has been making headway with an odor analysis technology. It will be part of a National Health Service trial that will test the sensor for diagnosing lung cancer. The company also is conducting a trial using urine samples to detect colon cancer; its program allows changing the software to change what disease you detect.
Meanwhile, an Israeli chemical engineer, Hossam Haick, is using similar technology, with molecular receptors that have an affinity for certain biomarkers of disease found in the breath. Artificial intelligence allows the sensors to improve with each use, and a paper published last year showed that this system could distinguish among 17 different diseases with up to 86% accuracy.
And in the United States, researchers from the Monell Chemical Senses Center and the University of Pennsylvania are working on an odor sensor that detects ovarian cancer in samples of blood plasma. They chose plasma because it is less likely than breath or urine to be affected by other factors such as diet or environmental chemicals.
These technologies could be available to doctors in 3-5 years, experts say.
Reference
Murphy K. One Day, a Machine Will Smell Whether You’re Sick . New York Times. May 1, 2017. Accessed May 29, 2017.
Smells – of skin, breath, or bodily fluids – can, in some cases, reveal the presence of disease. This fact has led researchers to try to build an odor sensor that could make a fast, reliable diagnosis, and now the field may be on the verge of a breakthrough, according to a recent article in the New York Times.
In addition to various efforts in Austria, Switzerland, and Japan, an English manufacturer – Owlstone Medical – has been making headway with an odor analysis technology. It will be part of a National Health Service trial that will test the sensor for diagnosing lung cancer. The company also is conducting a trial using urine samples to detect colon cancer; its program allows changing the software to change what disease you detect.
Meanwhile, an Israeli chemical engineer, Hossam Haick, is using similar technology, with molecular receptors that have an affinity for certain biomarkers of disease found in the breath. Artificial intelligence allows the sensors to improve with each use, and a paper published last year showed that this system could distinguish among 17 different diseases with up to 86% accuracy.
And in the United States, researchers from the Monell Chemical Senses Center and the University of Pennsylvania are working on an odor sensor that detects ovarian cancer in samples of blood plasma. They chose plasma because it is less likely than breath or urine to be affected by other factors such as diet or environmental chemicals.
These technologies could be available to doctors in 3-5 years, experts say.
Reference
Murphy K. One Day, a Machine Will Smell Whether You’re Sick . New York Times. May 1, 2017. Accessed May 29, 2017.
Ustekinumab may reduce risk of nonmelanoma skin cancer
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology. 
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Psoriasis patients on ustekinumab had an adjusted 65% reduction in the risk of developing nonmelanoma skin cancer compared with patients on methotrexate.
Data source: An analysis of 6,782 psoriasis patients participating in an international prospective observational registry evaluating the long-term safety and clinical outcomes of systemic therapies.
Disclosures: The PSOLAR registry is funded by ustekinumab manufacturer Janssen; the study presenter is a company employee.
Understanding the Causes of Venous Pressure
Developing an effective treatment plan for patients with venous disease hinges on an thorough clinical evaluation and a keen understanding of venous anatomy and physiology, both of which will be the focus of the Thursday morning session, “Venous Clinical Examination and Hemodynamics.”
“Less invasive treatments are now available because of the advent of new technologies,” said co-moderator Dr. Jose I. Almeida, director of the Miami Vein Center and voluntary professor of surgery at the University of Miami School of Medicine. “However, the proper treatment of patients with advanced venous disease has little to do with the new toys available on the shelf. Rather, it depends on a proper understanding of the fundamental problem: What causes increased venous pressure?”
Presentations will focus on answering that question. “Without an accurate physician assessment, one cannot apply an effective treatment plan for a patient with venous disease,” said Dr. Almeida. Session co-moderators include Dr. Lowell S. Kabnick, director of the New York University Vein Center, and Dr. Thomas W. Wakefield, vascular surgery section head at the University of Michigan Cardiovascular Center.
“The session begins with identifying symptoms and signs of venous disease, scoring the disease severity with a validated tool, and classifying the severity on a scale of one to six,” said Dr. Almeida, who starts off the session with his own review of the CEAP classification for venous disease – Clinical, Etiologic, Anatomic and Pathophysiologic – and the Venous Clinical Severity Score system. “Patient reported outcomes are now increasingly important to all stakeholders in venous disease space, and these principles will be summarized,” he said.
The session then moves into the anatomy and physiology of venous disorders. “Proper treatment hinges on the understanding of superficial reflux pathways and how to identify them with the ultrasound imaging,” said Dr. Almeida “Venous hypertension can also be caused by obstruction. The hemodynamics from the perspective of our European colleagues will be presented – and the controversial treatments used based on these hemodynamic principles will be reviewed.”
Dr. Bo G. Eklof of the University of Lund will provide the European perspective with an update on the Venous Symposium Consensus (SYMVein), a collaboration of the European Venous Forum and International Working Group to develop a consensus on venous symptoms.
Dr. Kabnick will then explore outcome assessment of central venous disease, and Dr. Wakefield will review the evidence on the pathophysiology of varicose veins. Dr. Seshadri Raju, vascular surgeon at St. Dominic Hospital will explore emerging concepts in venous flow and pressure.
“This will be the talk that ties in the concepts of flow and pressure and how each contributes to the final common pathway of venous disease—namely, venous hypertension,” Dr. Almeida said of Dr. Raju’s presentation.
In keeping with a deeper dive into venous anatomy, Dr. Neil M. Khilnani, associate professor of radiology at Weill Medical College of Cornell University, will discuss the role of duplex ultrasound in identifying reflux pathways, and Dr. Brajesh K. Lal, professor at University of Maryland School of Medicine, will present the latest evidence on venous return pathology. Then Dr. Byung-Boong Lee, professor of surgery at George Washington School of Medicine, will provide an update on the International Union of Phlebology consensus on chronic venous disease
Two presenters from the Riviera Vein Institute in the Principality of Monaco will close out the session. Research chair Dr. Sylvain Chastanet will present 10-year results of the ASVAL – the French acronym for selective ablation of varicose veins under local anesthesia – method for treating varicose veins. And Dr. Paul Pittaluga will wrap things up by analyzing the role of the saphenofemoral junction in planning treatment for varicose veins.
Developing an effective treatment plan for patients with venous disease hinges on an thorough clinical evaluation and a keen understanding of venous anatomy and physiology, both of which will be the focus of the Thursday morning session, “Venous Clinical Examination and Hemodynamics.”
“Less invasive treatments are now available because of the advent of new technologies,” said co-moderator Dr. Jose I. Almeida, director of the Miami Vein Center and voluntary professor of surgery at the University of Miami School of Medicine. “However, the proper treatment of patients with advanced venous disease has little to do with the new toys available on the shelf. Rather, it depends on a proper understanding of the fundamental problem: What causes increased venous pressure?”
Presentations will focus on answering that question. “Without an accurate physician assessment, one cannot apply an effective treatment plan for a patient with venous disease,” said Dr. Almeida. Session co-moderators include Dr. Lowell S. Kabnick, director of the New York University Vein Center, and Dr. Thomas W. Wakefield, vascular surgery section head at the University of Michigan Cardiovascular Center.
“The session begins with identifying symptoms and signs of venous disease, scoring the disease severity with a validated tool, and classifying the severity on a scale of one to six,” said Dr. Almeida, who starts off the session with his own review of the CEAP classification for venous disease – Clinical, Etiologic, Anatomic and Pathophysiologic – and the Venous Clinical Severity Score system. “Patient reported outcomes are now increasingly important to all stakeholders in venous disease space, and these principles will be summarized,” he said.
The session then moves into the anatomy and physiology of venous disorders. “Proper treatment hinges on the understanding of superficial reflux pathways and how to identify them with the ultrasound imaging,” said Dr. Almeida “Venous hypertension can also be caused by obstruction. The hemodynamics from the perspective of our European colleagues will be presented – and the controversial treatments used based on these hemodynamic principles will be reviewed.”
Dr. Bo G. Eklof of the University of Lund will provide the European perspective with an update on the Venous Symposium Consensus (SYMVein), a collaboration of the European Venous Forum and International Working Group to develop a consensus on venous symptoms.
Dr. Kabnick will then explore outcome assessment of central venous disease, and Dr. Wakefield will review the evidence on the pathophysiology of varicose veins. Dr. Seshadri Raju, vascular surgeon at St. Dominic Hospital will explore emerging concepts in venous flow and pressure.
“This will be the talk that ties in the concepts of flow and pressure and how each contributes to the final common pathway of venous disease—namely, venous hypertension,” Dr. Almeida said of Dr. Raju’s presentation.
In keeping with a deeper dive into venous anatomy, Dr. Neil M. Khilnani, associate professor of radiology at Weill Medical College of Cornell University, will discuss the role of duplex ultrasound in identifying reflux pathways, and Dr. Brajesh K. Lal, professor at University of Maryland School of Medicine, will present the latest evidence on venous return pathology. Then Dr. Byung-Boong Lee, professor of surgery at George Washington School of Medicine, will provide an update on the International Union of Phlebology consensus on chronic venous disease
Two presenters from the Riviera Vein Institute in the Principality of Monaco will close out the session. Research chair Dr. Sylvain Chastanet will present 10-year results of the ASVAL – the French acronym for selective ablation of varicose veins under local anesthesia – method for treating varicose veins. And Dr. Paul Pittaluga will wrap things up by analyzing the role of the saphenofemoral junction in planning treatment for varicose veins.
Developing an effective treatment plan for patients with venous disease hinges on an thorough clinical evaluation and a keen understanding of venous anatomy and physiology, both of which will be the focus of the Thursday morning session, “Venous Clinical Examination and Hemodynamics.”
“Less invasive treatments are now available because of the advent of new technologies,” said co-moderator Dr. Jose I. Almeida, director of the Miami Vein Center and voluntary professor of surgery at the University of Miami School of Medicine. “However, the proper treatment of patients with advanced venous disease has little to do with the new toys available on the shelf. Rather, it depends on a proper understanding of the fundamental problem: What causes increased venous pressure?”
Presentations will focus on answering that question. “Without an accurate physician assessment, one cannot apply an effective treatment plan for a patient with venous disease,” said Dr. Almeida. Session co-moderators include Dr. Lowell S. Kabnick, director of the New York University Vein Center, and Dr. Thomas W. Wakefield, vascular surgery section head at the University of Michigan Cardiovascular Center.
“The session begins with identifying symptoms and signs of venous disease, scoring the disease severity with a validated tool, and classifying the severity on a scale of one to six,” said Dr. Almeida, who starts off the session with his own review of the CEAP classification for venous disease – Clinical, Etiologic, Anatomic and Pathophysiologic – and the Venous Clinical Severity Score system. “Patient reported outcomes are now increasingly important to all stakeholders in venous disease space, and these principles will be summarized,” he said.
The session then moves into the anatomy and physiology of venous disorders. “Proper treatment hinges on the understanding of superficial reflux pathways and how to identify them with the ultrasound imaging,” said Dr. Almeida “Venous hypertension can also be caused by obstruction. The hemodynamics from the perspective of our European colleagues will be presented – and the controversial treatments used based on these hemodynamic principles will be reviewed.”
Dr. Bo G. Eklof of the University of Lund will provide the European perspective with an update on the Venous Symposium Consensus (SYMVein), a collaboration of the European Venous Forum and International Working Group to develop a consensus on venous symptoms.
Dr. Kabnick will then explore outcome assessment of central venous disease, and Dr. Wakefield will review the evidence on the pathophysiology of varicose veins. Dr. Seshadri Raju, vascular surgeon at St. Dominic Hospital will explore emerging concepts in venous flow and pressure.
“This will be the talk that ties in the concepts of flow and pressure and how each contributes to the final common pathway of venous disease—namely, venous hypertension,” Dr. Almeida said of Dr. Raju’s presentation.
In keeping with a deeper dive into venous anatomy, Dr. Neil M. Khilnani, associate professor of radiology at Weill Medical College of Cornell University, will discuss the role of duplex ultrasound in identifying reflux pathways, and Dr. Brajesh K. Lal, professor at University of Maryland School of Medicine, will present the latest evidence on venous return pathology. Then Dr. Byung-Boong Lee, professor of surgery at George Washington School of Medicine, will provide an update on the International Union of Phlebology consensus on chronic venous disease
Two presenters from the Riviera Vein Institute in the Principality of Monaco will close out the session. Research chair Dr. Sylvain Chastanet will present 10-year results of the ASVAL – the French acronym for selective ablation of varicose veins under local anesthesia – method for treating varicose veins. And Dr. Paul Pittaluga will wrap things up by analyzing the role of the saphenofemoral junction in planning treatment for varicose veins.
Nivolumab may extend survival in HCC patients
WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.
“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”
The dose-escalation cohort received 0.1 to 10 mg/kg of nivolumab (Opdivo) while the dose-expansion group received a steady dose of 3 mg/kg. In all, 262 patients participated in the trial, 80 of whom had never been on sorafenib (Nexavar) therapy. The survival outcome in these subgroups, Dr. Sangro said, “really speaks for the consistency and the robustness of the results.”
Trial participants had inoperable, usually metastatic HCC, with Child-Pugh scores up to and including 7 in the escalation group or up to and including 6 in the expansion group. Most of them were progressing to treatment with one or more prior systemic therapies, including sorafenib. Their aspartate aminotransferase and alanine aminotransferase scores were in the upper limits of normal, and bilirubin was less than or equal to 3 mg/dL. If they had hepatitis B (HBV), their viral load had to be less than 100 IU/mL and they had to be on effective antiviral therapy. Any history of hepatic encephalopathy or clinically significant ascites and an active HBV and hepatitis C (HCV) coinfection were grounds for exclusion.
“Most patients had to discontinue nivolumab because of disease progression,” Dr. Sangro noted, so that only 36 patients, or 14%, were continuing treatment at the time of this analysis. Thirteen patients in the total population that discontinued nivolumab did so because of toxicity, he said.
“Around 20% of patients achieved an objective remission that included complete responses in all subgroups of patients; 15% of progressors and 23% of sorafenib-intolerant patients had an objective response,” Dr. Sangro said. In terms of overall response, about half of all patients in the sorafenib-experienced subgroups had a complete or partial response or stable disease: 51% in the dose-escalation subgroup and 54% in the dose-expansion subgroup.
Although tumor responses were associated with declines in alpha-fetoprotein levels, “it’s unlikely that these biomarkers will be useful either for monitoring or selecting patients for treatment,” he added. “Indeed, baseline alpha-fetoprotein levels were comparable between responders and nonresponders to nivolumab” Dr. Sangro said.
“We also showed there was some impact on HCV viral kinetics in infected individuals,” Dr. Sangro noted. “The overall safety profile for the HCC population is consistent with other tumor types in which nivolumab is approved; these include patients who are infected with hepatitis B or C viruses.”
The study showed that 36% (19/53) of HCV infected patients had a greater than 1 log decrease in viral load. No signs of additional antiviral activity were detected among HBV-infected patients already on effective antiviral treatment: only 5% (3/59) posted a up to 1 log decrease in HB surface antigen levels, and 11% (7/64) of patients had increases in viral load. “These increases occurred in the setting of low-level viremia.” Dr. Sangro said. “They were asymptomatic and [nivolumab] did not result in changes in hepatic parameters or other serious adverse events.”
With regard to adverse events (AEs), 77% of all patients had some treatment-related AEs, ranging from fatigue to rash to dry mouth to increased lab levels, but only 20% were grade 3 or 4, and 88% of those resolved in an average of 8 weeks, Dr. Sangro said.
More research into nivolumab for HCC is needed, Dr. Sangro said. “Ongoing and future studies in patients with advanced tumors will evaluate nivolumab in the first-line setting or in combination with other agents,” he said.
Dr. Sangro disclosed relationships with Bayer Schering Pharma, Onxeo, Astra Zeneca, and Bristol-Myers Squibb. Bristol-Myers Squibb funded the trial, and Chrysalis Medical Communications assisted in reporting the study results.
WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.
“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”
The dose-escalation cohort received 0.1 to 10 mg/kg of nivolumab (Opdivo) while the dose-expansion group received a steady dose of 3 mg/kg. In all, 262 patients participated in the trial, 80 of whom had never been on sorafenib (Nexavar) therapy. The survival outcome in these subgroups, Dr. Sangro said, “really speaks for the consistency and the robustness of the results.”
Trial participants had inoperable, usually metastatic HCC, with Child-Pugh scores up to and including 7 in the escalation group or up to and including 6 in the expansion group. Most of them were progressing to treatment with one or more prior systemic therapies, including sorafenib. Their aspartate aminotransferase and alanine aminotransferase scores were in the upper limits of normal, and bilirubin was less than or equal to 3 mg/dL. If they had hepatitis B (HBV), their viral load had to be less than 100 IU/mL and they had to be on effective antiviral therapy. Any history of hepatic encephalopathy or clinically significant ascites and an active HBV and hepatitis C (HCV) coinfection were grounds for exclusion.
“Most patients had to discontinue nivolumab because of disease progression,” Dr. Sangro noted, so that only 36 patients, or 14%, were continuing treatment at the time of this analysis. Thirteen patients in the total population that discontinued nivolumab did so because of toxicity, he said.
“Around 20% of patients achieved an objective remission that included complete responses in all subgroups of patients; 15% of progressors and 23% of sorafenib-intolerant patients had an objective response,” Dr. Sangro said. In terms of overall response, about half of all patients in the sorafenib-experienced subgroups had a complete or partial response or stable disease: 51% in the dose-escalation subgroup and 54% in the dose-expansion subgroup.
Although tumor responses were associated with declines in alpha-fetoprotein levels, “it’s unlikely that these biomarkers will be useful either for monitoring or selecting patients for treatment,” he added. “Indeed, baseline alpha-fetoprotein levels were comparable between responders and nonresponders to nivolumab” Dr. Sangro said.
“We also showed there was some impact on HCV viral kinetics in infected individuals,” Dr. Sangro noted. “The overall safety profile for the HCC population is consistent with other tumor types in which nivolumab is approved; these include patients who are infected with hepatitis B or C viruses.”
The study showed that 36% (19/53) of HCV infected patients had a greater than 1 log decrease in viral load. No signs of additional antiviral activity were detected among HBV-infected patients already on effective antiviral treatment: only 5% (3/59) posted a up to 1 log decrease in HB surface antigen levels, and 11% (7/64) of patients had increases in viral load. “These increases occurred in the setting of low-level viremia.” Dr. Sangro said. “They were asymptomatic and [nivolumab] did not result in changes in hepatic parameters or other serious adverse events.”
With regard to adverse events (AEs), 77% of all patients had some treatment-related AEs, ranging from fatigue to rash to dry mouth to increased lab levels, but only 20% were grade 3 or 4, and 88% of those resolved in an average of 8 weeks, Dr. Sangro said.
More research into nivolumab for HCC is needed, Dr. Sangro said. “Ongoing and future studies in patients with advanced tumors will evaluate nivolumab in the first-line setting or in combination with other agents,” he said.
Dr. Sangro disclosed relationships with Bayer Schering Pharma, Onxeo, Astra Zeneca, and Bristol-Myers Squibb. Bristol-Myers Squibb funded the trial, and Chrysalis Medical Communications assisted in reporting the study results.
WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.
“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”
The dose-escalation cohort received 0.1 to 10 mg/kg of nivolumab (Opdivo) while the dose-expansion group received a steady dose of 3 mg/kg. In all, 262 patients participated in the trial, 80 of whom had never been on sorafenib (Nexavar) therapy. The survival outcome in these subgroups, Dr. Sangro said, “really speaks for the consistency and the robustness of the results.”
Trial participants had inoperable, usually metastatic HCC, with Child-Pugh scores up to and including 7 in the escalation group or up to and including 6 in the expansion group. Most of them were progressing to treatment with one or more prior systemic therapies, including sorafenib. Their aspartate aminotransferase and alanine aminotransferase scores were in the upper limits of normal, and bilirubin was less than or equal to 3 mg/dL. If they had hepatitis B (HBV), their viral load had to be less than 100 IU/mL and they had to be on effective antiviral therapy. Any history of hepatic encephalopathy or clinically significant ascites and an active HBV and hepatitis C (HCV) coinfection were grounds for exclusion.
“Most patients had to discontinue nivolumab because of disease progression,” Dr. Sangro noted, so that only 36 patients, or 14%, were continuing treatment at the time of this analysis. Thirteen patients in the total population that discontinued nivolumab did so because of toxicity, he said.
“Around 20% of patients achieved an objective remission that included complete responses in all subgroups of patients; 15% of progressors and 23% of sorafenib-intolerant patients had an objective response,” Dr. Sangro said. In terms of overall response, about half of all patients in the sorafenib-experienced subgroups had a complete or partial response or stable disease: 51% in the dose-escalation subgroup and 54% in the dose-expansion subgroup.
Although tumor responses were associated with declines in alpha-fetoprotein levels, “it’s unlikely that these biomarkers will be useful either for monitoring or selecting patients for treatment,” he added. “Indeed, baseline alpha-fetoprotein levels were comparable between responders and nonresponders to nivolumab” Dr. Sangro said.
“We also showed there was some impact on HCV viral kinetics in infected individuals,” Dr. Sangro noted. “The overall safety profile for the HCC population is consistent with other tumor types in which nivolumab is approved; these include patients who are infected with hepatitis B or C viruses.”
The study showed that 36% (19/53) of HCV infected patients had a greater than 1 log decrease in viral load. No signs of additional antiviral activity were detected among HBV-infected patients already on effective antiviral treatment: only 5% (3/59) posted a up to 1 log decrease in HB surface antigen levels, and 11% (7/64) of patients had increases in viral load. “These increases occurred in the setting of low-level viremia.” Dr. Sangro said. “They were asymptomatic and [nivolumab] did not result in changes in hepatic parameters or other serious adverse events.”
With regard to adverse events (AEs), 77% of all patients had some treatment-related AEs, ranging from fatigue to rash to dry mouth to increased lab levels, but only 20% were grade 3 or 4, and 88% of those resolved in an average of 8 weeks, Dr. Sangro said.
More research into nivolumab for HCC is needed, Dr. Sangro said. “Ongoing and future studies in patients with advanced tumors will evaluate nivolumab in the first-line setting or in combination with other agents,” he said.
Dr. Sangro disclosed relationships with Bayer Schering Pharma, Onxeo, Astra Zeneca, and Bristol-Myers Squibb. Bristol-Myers Squibb funded the trial, and Chrysalis Medical Communications assisted in reporting the study results.
AT THE LIVER MEETING 2017
Key clinical point: Nivolumab demonstrated long-term survival, durable tumor responses, and manageable overall and hepatic safety profiles, regardless of prior sorafenib treatment, in patients with advanced hepatocellular carcinoma.
Major finding: The 18-month overall survival rate was 57% in sorafenib-naive patients and 46% (dose-escalation) and 44% (dose-expansion) in sorafenib-experienced patients.
Data source: CheckMate-040 phase 1/2 dose-escalation and -expansion trial of 262 patients.
Disclosures: Dr. Sangro disclosed relationships with Bayer Schering Pharma, Onxeo, Astra Zeneca, and Bristol-Myers Squibb. Bristol-Myers Squibb funded the trial, and Chrysalis Medical Communications assisted in reporting the study results.
‘Facebuddha’ analyzes psychology of social media through a Buddhist lens
The new book by Ravi Chandra, MD, is a concise introduction to Buddhism, and a forceful exposition on the power and danger of social networking – deftly interwoven with a moving account of the author’s personal life and professional growth as well as his arduous quest for identity.
Social networking has exploded into a major global industry within the last decade, rapidly penetrating and dominating all aspects of our personal and social lives. Instead of promoting social interactions and connections, the lure of instant intimacy often proves illusory. For far too many, the virtual world deepens their sense of isolation and loneliness, fosters jealousy and narcissism, engenders a profound sense of insecurity, and leads to anxiety, depression, and much worse.
By juxtaposing the Buddha with social networking in the book title, Dr. Chandra expresses his hope and faith that Buddhism could serve as an effective tool for harnessing the force unleashed by these powerful new technologies, helping us to put the genie of our invention back into the bottle. Over the millenia, Buddhism has guided societies and individuals to overcome (“transcend”) crises and adversities, and could play a crucial role in negotiating these still largely uncharted territories.
Despite the popularity of terms such as Zen, meditation, transcendence, and mindfulness, Buddhism remains mysterious and exotic to most modern readers, and is laden with misconceptions and prejudices. This is regrettable, since Buddhism is the most clinically relevant of all major philosophical traditions, and its tenets are most compatible with modern neuroscience. The term philosophical is used here because, at its core, Buddhism represents an uncompromisingly rational approach to dealing with the “human condition.” Siddhartha Gautama (Buddha), its founder, admonished against speculating on questions that are “unanswerables,” such as eternity, existence after death, and the origin and ending of the universe. Instead, Siddhartha focused on identifying life’s vicissitudes (Dukkha, “bumpy rides in life,” commonly translated as “suffering”), clarifying forces responsible for these problems, delineating the ultimate goal, and specifying methods for achieving the goal (the “Four Noble Truths”). He then provided systematic paths for solving problems (the “Eightfold Noble Path”). His approaches are akin to what we clinicians strive to do on a daily basis, albeit on a grander scale: diagnosis, pathogenesis, treatment goals, and therapeutic approaches. The framework Siddhartha proposed is austere, rational, practical. It is exactly for this reason that Siddhartha has been called a great physician, a doctor, and a healer.
As a psychiatrist and a practicing Buddhist, Dr. Chandra is well positioned to critically examine these profoundly important issues (Buddhism and social networking), and he did an excellent job in “Facebuddha.” Impressively, Dr. Chandra’s discussions did not take place in a vacuum. They were not just dry intellectual exercises but were embedded in accounts of personal and clinical experiences, demonstrating the relevance of Buddhist thoughts and practices in real life.
Born in South India and raised by a physician mother in half a dozen American cities, Dr. Chandra experienced repeated uprooting and various types of racial/cultural discrimination. His childhood and adolescence were characterized by a long and arduous search for identity. That he has not only survived, but thrived, is a testament to his resilience and resourcefulness. His love of art and poetry played an important role, as did friendships and the support of Asian American communities. But, above all, it was the Buddha’s teachings and examples that have been the most significant sustaining forces in his life. His accounts are a personal testimony to the power of a 2,500-year-old tradition that is still alive and relevant in our postmodern world.
Dr. Chandra’s book is an endearing chronicle of a remarkable personal journey. Readers will appreciate the opportunity to witness glimpses of this journey and may reasonably expect that such explorations will continue, leading to new vistas that are not only fascinating to behold but also relevant to the practice of our profession.
Dr. Lin is professor emeritus of psychiatry, University of California, Los Angeles, and Distinguished Life Fellow, American Psychiatric Association. He was the founding director of the National Institute of Mental Health/Harbor-UCLA Research Center on the Psychobiology of Ethnicity, the Coastal Asian Pacific Mental Health Center, and the Long Beach Asian Pacific Mental Health Center. The honors Dr. Lin has received include the Kun-Po Soo Asian American Award, American Psychiatric Association; William Sargant Lecturer, Royal College of Psychiatrists, Great Britain; and honorary professor, Hunan (China) Medical University. Information about the book can be found at www.facebuddha.co.
The new book by Ravi Chandra, MD, is a concise introduction to Buddhism, and a forceful exposition on the power and danger of social networking – deftly interwoven with a moving account of the author’s personal life and professional growth as well as his arduous quest for identity.
Social networking has exploded into a major global industry within the last decade, rapidly penetrating and dominating all aspects of our personal and social lives. Instead of promoting social interactions and connections, the lure of instant intimacy often proves illusory. For far too many, the virtual world deepens their sense of isolation and loneliness, fosters jealousy and narcissism, engenders a profound sense of insecurity, and leads to anxiety, depression, and much worse.
By juxtaposing the Buddha with social networking in the book title, Dr. Chandra expresses his hope and faith that Buddhism could serve as an effective tool for harnessing the force unleashed by these powerful new technologies, helping us to put the genie of our invention back into the bottle. Over the millenia, Buddhism has guided societies and individuals to overcome (“transcend”) crises and adversities, and could play a crucial role in negotiating these still largely uncharted territories.
Despite the popularity of terms such as Zen, meditation, transcendence, and mindfulness, Buddhism remains mysterious and exotic to most modern readers, and is laden with misconceptions and prejudices. This is regrettable, since Buddhism is the most clinically relevant of all major philosophical traditions, and its tenets are most compatible with modern neuroscience. The term philosophical is used here because, at its core, Buddhism represents an uncompromisingly rational approach to dealing with the “human condition.” Siddhartha Gautama (Buddha), its founder, admonished against speculating on questions that are “unanswerables,” such as eternity, existence after death, and the origin and ending of the universe. Instead, Siddhartha focused on identifying life’s vicissitudes (Dukkha, “bumpy rides in life,” commonly translated as “suffering”), clarifying forces responsible for these problems, delineating the ultimate goal, and specifying methods for achieving the goal (the “Four Noble Truths”). He then provided systematic paths for solving problems (the “Eightfold Noble Path”). His approaches are akin to what we clinicians strive to do on a daily basis, albeit on a grander scale: diagnosis, pathogenesis, treatment goals, and therapeutic approaches. The framework Siddhartha proposed is austere, rational, practical. It is exactly for this reason that Siddhartha has been called a great physician, a doctor, and a healer.
As a psychiatrist and a practicing Buddhist, Dr. Chandra is well positioned to critically examine these profoundly important issues (Buddhism and social networking), and he did an excellent job in “Facebuddha.” Impressively, Dr. Chandra’s discussions did not take place in a vacuum. They were not just dry intellectual exercises but were embedded in accounts of personal and clinical experiences, demonstrating the relevance of Buddhist thoughts and practices in real life.
Born in South India and raised by a physician mother in half a dozen American cities, Dr. Chandra experienced repeated uprooting and various types of racial/cultural discrimination. His childhood and adolescence were characterized by a long and arduous search for identity. That he has not only survived, but thrived, is a testament to his resilience and resourcefulness. His love of art and poetry played an important role, as did friendships and the support of Asian American communities. But, above all, it was the Buddha’s teachings and examples that have been the most significant sustaining forces in his life. His accounts are a personal testimony to the power of a 2,500-year-old tradition that is still alive and relevant in our postmodern world.
Dr. Chandra’s book is an endearing chronicle of a remarkable personal journey. Readers will appreciate the opportunity to witness glimpses of this journey and may reasonably expect that such explorations will continue, leading to new vistas that are not only fascinating to behold but also relevant to the practice of our profession.
Dr. Lin is professor emeritus of psychiatry, University of California, Los Angeles, and Distinguished Life Fellow, American Psychiatric Association. He was the founding director of the National Institute of Mental Health/Harbor-UCLA Research Center on the Psychobiology of Ethnicity, the Coastal Asian Pacific Mental Health Center, and the Long Beach Asian Pacific Mental Health Center. The honors Dr. Lin has received include the Kun-Po Soo Asian American Award, American Psychiatric Association; William Sargant Lecturer, Royal College of Psychiatrists, Great Britain; and honorary professor, Hunan (China) Medical University. Information about the book can be found at www.facebuddha.co.
The new book by Ravi Chandra, MD, is a concise introduction to Buddhism, and a forceful exposition on the power and danger of social networking – deftly interwoven with a moving account of the author’s personal life and professional growth as well as his arduous quest for identity.
Social networking has exploded into a major global industry within the last decade, rapidly penetrating and dominating all aspects of our personal and social lives. Instead of promoting social interactions and connections, the lure of instant intimacy often proves illusory. For far too many, the virtual world deepens their sense of isolation and loneliness, fosters jealousy and narcissism, engenders a profound sense of insecurity, and leads to anxiety, depression, and much worse.
By juxtaposing the Buddha with social networking in the book title, Dr. Chandra expresses his hope and faith that Buddhism could serve as an effective tool for harnessing the force unleashed by these powerful new technologies, helping us to put the genie of our invention back into the bottle. Over the millenia, Buddhism has guided societies and individuals to overcome (“transcend”) crises and adversities, and could play a crucial role in negotiating these still largely uncharted territories.
Despite the popularity of terms such as Zen, meditation, transcendence, and mindfulness, Buddhism remains mysterious and exotic to most modern readers, and is laden with misconceptions and prejudices. This is regrettable, since Buddhism is the most clinically relevant of all major philosophical traditions, and its tenets are most compatible with modern neuroscience. The term philosophical is used here because, at its core, Buddhism represents an uncompromisingly rational approach to dealing with the “human condition.” Siddhartha Gautama (Buddha), its founder, admonished against speculating on questions that are “unanswerables,” such as eternity, existence after death, and the origin and ending of the universe. Instead, Siddhartha focused on identifying life’s vicissitudes (Dukkha, “bumpy rides in life,” commonly translated as “suffering”), clarifying forces responsible for these problems, delineating the ultimate goal, and specifying methods for achieving the goal (the “Four Noble Truths”). He then provided systematic paths for solving problems (the “Eightfold Noble Path”). His approaches are akin to what we clinicians strive to do on a daily basis, albeit on a grander scale: diagnosis, pathogenesis, treatment goals, and therapeutic approaches. The framework Siddhartha proposed is austere, rational, practical. It is exactly for this reason that Siddhartha has been called a great physician, a doctor, and a healer.
As a psychiatrist and a practicing Buddhist, Dr. Chandra is well positioned to critically examine these profoundly important issues (Buddhism and social networking), and he did an excellent job in “Facebuddha.” Impressively, Dr. Chandra’s discussions did not take place in a vacuum. They were not just dry intellectual exercises but were embedded in accounts of personal and clinical experiences, demonstrating the relevance of Buddhist thoughts and practices in real life.
Born in South India and raised by a physician mother in half a dozen American cities, Dr. Chandra experienced repeated uprooting and various types of racial/cultural discrimination. His childhood and adolescence were characterized by a long and arduous search for identity. That he has not only survived, but thrived, is a testament to his resilience and resourcefulness. His love of art and poetry played an important role, as did friendships and the support of Asian American communities. But, above all, it was the Buddha’s teachings and examples that have been the most significant sustaining forces in his life. His accounts are a personal testimony to the power of a 2,500-year-old tradition that is still alive and relevant in our postmodern world.
Dr. Chandra’s book is an endearing chronicle of a remarkable personal journey. Readers will appreciate the opportunity to witness glimpses of this journey and may reasonably expect that such explorations will continue, leading to new vistas that are not only fascinating to behold but also relevant to the practice of our profession.
Dr. Lin is professor emeritus of psychiatry, University of California, Los Angeles, and Distinguished Life Fellow, American Psychiatric Association. He was the founding director of the National Institute of Mental Health/Harbor-UCLA Research Center on the Psychobiology of Ethnicity, the Coastal Asian Pacific Mental Health Center, and the Long Beach Asian Pacific Mental Health Center. The honors Dr. Lin has received include the Kun-Po Soo Asian American Award, American Psychiatric Association; William Sargant Lecturer, Royal College of Psychiatrists, Great Britain; and honorary professor, Hunan (China) Medical University. Information about the book can be found at www.facebuddha.co.
Nemolizumab continues to crush itch in 64-week atopic dermatitis study
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
AT THE EADV CONGRESS
Key clinical point:
Major finding: The early dramatic antipruritic effect demonstrated by nemolizumab for atopic dermatitis in a 12-week randomized trial was maintained throughout an additional 52 weeks in an extension study.
Data source: This analysis focused on 211 patients with moderate to severe atopic dermatitis who participated in a 52-week open-label extension study after completing a previously reported 12-week, double-blind, placebo-controlled phase.
Disclosures: The presenter is a paid medical adviser to Chugai Pharmaceutical, which funded the study.
Top research to be presented at AAGL
The 46th AAGL Global Congress on Minimally Invasive Gynecologic Surgery starts Nov. 12, 2017, in National Harbor, Md., and attendees will have a chance to hear presentations on more than 300 studies, plus numerous virtual posters.
Dr. Charles E. Miller, a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL, offered his top picks for not-to-be-missed research at this year’s meeting.
Cesarean-induced isthmoceles
On Wednesday, Nov. 15, at 12:17 p.m., researchers from West Virginia University in Morgantown and Universidad Autónoma de Nuevo León in Mexico will present data from a prospective study on the anatomy of cesarean-induced isthmoceles. The paper won the Golden Hysteroscope Award for best paper on hysteroscopy. It is being presented during the Open Communications 13 session on reproductive medicine.
“Isthmocele has become such a hot topic,” Dr. Miller said. “Besides the implications in terms of pelvic pain and abnormal bleeding, it can be a cause of infertility as fluid goes into the endometrial cavity and impacts implantation.”
Dr. Miller will be performing a telesurgery featuring robotic-assisted excision and repair of a cesarean section isthmocele on Thursday, Nov. 16, as part of General Session V from 8:30 a.m. to 12:30 p.m.
Rectosigmoid endometriosis
On Wednesday, Nov. 15, at 12:50 p.m., researchers from the University of Pittsburgh will show a surgical video on anterior discoid resection for rectosigmoid endometriosis. They use various laparoscopic instruments and techniques to assess and resect the nodule, including a “squeeze” technique, barbed suture, and a V-shaped closure. The video, which won the Golden Laparoscope Award for best surgical video, is being presented during the Plenary 6 session on endometriosis and adenomyosis.
“There is great debate in just how aggressively patients should be treated when a woman has deep infiltrative endometriosis involving the rectosigmoid area,” Dr. Miller said.
Most of the research in this area is from single-institution studies that do not always completely describe the procedure, leaving surgeons “unsure of which way to go,” Dr. Miller said. In addition, because many patients with endometriosis are young, surgeons need to consider how the procedure will impact them in 20 or even 50 years. While more aggressive than shaving, discoid resection is less aggressive than standard bowel resection.
Postsurgical pain control
On Tuesday, Nov. 14, at 3:46 p.m., researchers from the University of Pittsburgh, Oregon Health & Science University, Southern California Permanente Medical Group, and the University of Wisconsin, Madison, will present results from a prospective, double-blind, randomized study comparing intravenous acetaminophen with placebo for postsurgical pain control and patient satisfaction after laparoscopic hysterectomy. Their findings indicate no difference in either pain or satisfaction, casting doubt on routine use during hysterectomy. The study, which won the Jay M. Cooper Award for best paper on minimally invasive gynecology by a fellow, will be presented during the Open Communications 9 session on laparoscopy.
On Tuesday, Nov. 14, at 1:21 p.m., researchers from the University of Maryland, Baltimore; Mercy Medical Center, Baltimore; and Yoyodyne General Services, New York, will present a single-center, double-blind, randomized, placebo-controlled trial to assess the use of a single belladonna and opium suppository placed after laparoscopic or robotic hysterectomy to control postoperative pain. As with acetaminophen, they also found that the suppositories did not significantly lower pain or narcotic use. However, the belladonna/opium suppository reduced time to discharge from the postanesthesia care unit in phase I. The research, which won the Jerome J. Hoffman Award for best abstract by a resident or fellow, will be presented during Session 2 of the Virtual Posters.
“Here again are two treatments that really have minimal basis,” Dr. Miller said. “In the days of cost containment, is there really any reason for either?”
Cervical ripening
Dr. Miller also recommended that attendees take note of a randomized controlled trial evaluating whether misoprostol oral is as effective as vaginal tablets for cervical ripening. Researchers at Cairo University in Egypt considered this question among more than 350 women who were undergoing operative hysterectomy for various indications. They found no statistically significant difference in efficacy and similar adverse effects.
“There has been some concern raised about, is there a better way?” Dr. Miller said. “This is especially important as we move hysteroscopy to the office.”
The cervical priming study, which won the Robert B. Hunt Award for best paper published in the Journal of Minimally Invasive Gynecology between September 2016 and August 2017, will be presented on Tuesday, Nov. 14, at 7:10 a.m. during the journal’s editorial/advisory board breakfast. You can read the full article online (J Minim Invasive Gynecol. 2016 Nov - Dec;23[7]:1107-12).
[email protected]
On Twitter @maryellenny
The 46th AAGL Global Congress on Minimally Invasive Gynecologic Surgery starts Nov. 12, 2017, in National Harbor, Md., and attendees will have a chance to hear presentations on more than 300 studies, plus numerous virtual posters.
Dr. Charles E. Miller, a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL, offered his top picks for not-to-be-missed research at this year’s meeting.
Cesarean-induced isthmoceles
On Wednesday, Nov. 15, at 12:17 p.m., researchers from West Virginia University in Morgantown and Universidad Autónoma de Nuevo León in Mexico will present data from a prospective study on the anatomy of cesarean-induced isthmoceles. The paper won the Golden Hysteroscope Award for best paper on hysteroscopy. It is being presented during the Open Communications 13 session on reproductive medicine.
“Isthmocele has become such a hot topic,” Dr. Miller said. “Besides the implications in terms of pelvic pain and abnormal bleeding, it can be a cause of infertility as fluid goes into the endometrial cavity and impacts implantation.”
Dr. Miller will be performing a telesurgery featuring robotic-assisted excision and repair of a cesarean section isthmocele on Thursday, Nov. 16, as part of General Session V from 8:30 a.m. to 12:30 p.m.
Rectosigmoid endometriosis
On Wednesday, Nov. 15, at 12:50 p.m., researchers from the University of Pittsburgh will show a surgical video on anterior discoid resection for rectosigmoid endometriosis. They use various laparoscopic instruments and techniques to assess and resect the nodule, including a “squeeze” technique, barbed suture, and a V-shaped closure. The video, which won the Golden Laparoscope Award for best surgical video, is being presented during the Plenary 6 session on endometriosis and adenomyosis.
“There is great debate in just how aggressively patients should be treated when a woman has deep infiltrative endometriosis involving the rectosigmoid area,” Dr. Miller said.
Most of the research in this area is from single-institution studies that do not always completely describe the procedure, leaving surgeons “unsure of which way to go,” Dr. Miller said. In addition, because many patients with endometriosis are young, surgeons need to consider how the procedure will impact them in 20 or even 50 years. While more aggressive than shaving, discoid resection is less aggressive than standard bowel resection.
Postsurgical pain control
On Tuesday, Nov. 14, at 3:46 p.m., researchers from the University of Pittsburgh, Oregon Health & Science University, Southern California Permanente Medical Group, and the University of Wisconsin, Madison, will present results from a prospective, double-blind, randomized study comparing intravenous acetaminophen with placebo for postsurgical pain control and patient satisfaction after laparoscopic hysterectomy. Their findings indicate no difference in either pain or satisfaction, casting doubt on routine use during hysterectomy. The study, which won the Jay M. Cooper Award for best paper on minimally invasive gynecology by a fellow, will be presented during the Open Communications 9 session on laparoscopy.
On Tuesday, Nov. 14, at 1:21 p.m., researchers from the University of Maryland, Baltimore; Mercy Medical Center, Baltimore; and Yoyodyne General Services, New York, will present a single-center, double-blind, randomized, placebo-controlled trial to assess the use of a single belladonna and opium suppository placed after laparoscopic or robotic hysterectomy to control postoperative pain. As with acetaminophen, they also found that the suppositories did not significantly lower pain or narcotic use. However, the belladonna/opium suppository reduced time to discharge from the postanesthesia care unit in phase I. The research, which won the Jerome J. Hoffman Award for best abstract by a resident or fellow, will be presented during Session 2 of the Virtual Posters.
“Here again are two treatments that really have minimal basis,” Dr. Miller said. “In the days of cost containment, is there really any reason for either?”
Cervical ripening
Dr. Miller also recommended that attendees take note of a randomized controlled trial evaluating whether misoprostol oral is as effective as vaginal tablets for cervical ripening. Researchers at Cairo University in Egypt considered this question among more than 350 women who were undergoing operative hysterectomy for various indications. They found no statistically significant difference in efficacy and similar adverse effects.
“There has been some concern raised about, is there a better way?” Dr. Miller said. “This is especially important as we move hysteroscopy to the office.”
The cervical priming study, which won the Robert B. Hunt Award for best paper published in the Journal of Minimally Invasive Gynecology between September 2016 and August 2017, will be presented on Tuesday, Nov. 14, at 7:10 a.m. during the journal’s editorial/advisory board breakfast. You can read the full article online (J Minim Invasive Gynecol. 2016 Nov - Dec;23[7]:1107-12).
[email protected]
On Twitter @maryellenny
The 46th AAGL Global Congress on Minimally Invasive Gynecologic Surgery starts Nov. 12, 2017, in National Harbor, Md., and attendees will have a chance to hear presentations on more than 300 studies, plus numerous virtual posters.
Dr. Charles E. Miller, a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL, offered his top picks for not-to-be-missed research at this year’s meeting.
Cesarean-induced isthmoceles
On Wednesday, Nov. 15, at 12:17 p.m., researchers from West Virginia University in Morgantown and Universidad Autónoma de Nuevo León in Mexico will present data from a prospective study on the anatomy of cesarean-induced isthmoceles. The paper won the Golden Hysteroscope Award for best paper on hysteroscopy. It is being presented during the Open Communications 13 session on reproductive medicine.
“Isthmocele has become such a hot topic,” Dr. Miller said. “Besides the implications in terms of pelvic pain and abnormal bleeding, it can be a cause of infertility as fluid goes into the endometrial cavity and impacts implantation.”
Dr. Miller will be performing a telesurgery featuring robotic-assisted excision and repair of a cesarean section isthmocele on Thursday, Nov. 16, as part of General Session V from 8:30 a.m. to 12:30 p.m.
Rectosigmoid endometriosis
On Wednesday, Nov. 15, at 12:50 p.m., researchers from the University of Pittsburgh will show a surgical video on anterior discoid resection for rectosigmoid endometriosis. They use various laparoscopic instruments and techniques to assess and resect the nodule, including a “squeeze” technique, barbed suture, and a V-shaped closure. The video, which won the Golden Laparoscope Award for best surgical video, is being presented during the Plenary 6 session on endometriosis and adenomyosis.
“There is great debate in just how aggressively patients should be treated when a woman has deep infiltrative endometriosis involving the rectosigmoid area,” Dr. Miller said.
Most of the research in this area is from single-institution studies that do not always completely describe the procedure, leaving surgeons “unsure of which way to go,” Dr. Miller said. In addition, because many patients with endometriosis are young, surgeons need to consider how the procedure will impact them in 20 or even 50 years. While more aggressive than shaving, discoid resection is less aggressive than standard bowel resection.
Postsurgical pain control
On Tuesday, Nov. 14, at 3:46 p.m., researchers from the University of Pittsburgh, Oregon Health & Science University, Southern California Permanente Medical Group, and the University of Wisconsin, Madison, will present results from a prospective, double-blind, randomized study comparing intravenous acetaminophen with placebo for postsurgical pain control and patient satisfaction after laparoscopic hysterectomy. Their findings indicate no difference in either pain or satisfaction, casting doubt on routine use during hysterectomy. The study, which won the Jay M. Cooper Award for best paper on minimally invasive gynecology by a fellow, will be presented during the Open Communications 9 session on laparoscopy.
On Tuesday, Nov. 14, at 1:21 p.m., researchers from the University of Maryland, Baltimore; Mercy Medical Center, Baltimore; and Yoyodyne General Services, New York, will present a single-center, double-blind, randomized, placebo-controlled trial to assess the use of a single belladonna and opium suppository placed after laparoscopic or robotic hysterectomy to control postoperative pain. As with acetaminophen, they also found that the suppositories did not significantly lower pain or narcotic use. However, the belladonna/opium suppository reduced time to discharge from the postanesthesia care unit in phase I. The research, which won the Jerome J. Hoffman Award for best abstract by a resident or fellow, will be presented during Session 2 of the Virtual Posters.
“Here again are two treatments that really have minimal basis,” Dr. Miller said. “In the days of cost containment, is there really any reason for either?”
Cervical ripening
Dr. Miller also recommended that attendees take note of a randomized controlled trial evaluating whether misoprostol oral is as effective as vaginal tablets for cervical ripening. Researchers at Cairo University in Egypt considered this question among more than 350 women who were undergoing operative hysterectomy for various indications. They found no statistically significant difference in efficacy and similar adverse effects.
“There has been some concern raised about, is there a better way?” Dr. Miller said. “This is especially important as we move hysteroscopy to the office.”
The cervical priming study, which won the Robert B. Hunt Award for best paper published in the Journal of Minimally Invasive Gynecology between September 2016 and August 2017, will be presented on Tuesday, Nov. 14, at 7:10 a.m. during the journal’s editorial/advisory board breakfast. You can read the full article online (J Minim Invasive Gynecol. 2016 Nov - Dec;23[7]:1107-12).
[email protected]
On Twitter @maryellenny
Case study suggests maternal inheritance of PBC susceptibility
A case report involving a family with four sisters with primary biliary cholangitis (PBC) suggests that there may be a maternal inheritance of susceptibility, according to Saeam Shin, MD, and associates at Hallym University in Seoul, South Korea.
In the first case, a 56-year-old woman was diagnosed with PBC, and afterwards, her three sisters, her brother, and her half-sister born to a different mother were evaluated for PBC as well. The second and fourth sisters showed no symptoms, but they were antimitochondrial-antibody (AMA) positive and were diagnosed with PBC. The third sister had been admitted to a different hospital for acute hepatitis of unknown origin – after receiving a positive AMA test, she also was diagnosed with PBC.
The brother and half-sister evaluated for PBC showed no symptoms and had negative AMA tests. The four sisters diagnosed showed good response to ursodeoxycholic acid in liver biochemistry tests and have continued on that medication without complication.
“If one patient is diagnosed with PBC, screening with AMA and liver function tests should be recommended to other family members for the early detection and management of this condition, especially for female relatives,” the investigators wrote.
Find the full case report in the World Journal of Gastroenterology (doi: 10.3748/wjg.v23.i39.7191).
A case report involving a family with four sisters with primary biliary cholangitis (PBC) suggests that there may be a maternal inheritance of susceptibility, according to Saeam Shin, MD, and associates at Hallym University in Seoul, South Korea.
In the first case, a 56-year-old woman was diagnosed with PBC, and afterwards, her three sisters, her brother, and her half-sister born to a different mother were evaluated for PBC as well. The second and fourth sisters showed no symptoms, but they were antimitochondrial-antibody (AMA) positive and were diagnosed with PBC. The third sister had been admitted to a different hospital for acute hepatitis of unknown origin – after receiving a positive AMA test, she also was diagnosed with PBC.
The brother and half-sister evaluated for PBC showed no symptoms and had negative AMA tests. The four sisters diagnosed showed good response to ursodeoxycholic acid in liver biochemistry tests and have continued on that medication without complication.
“If one patient is diagnosed with PBC, screening with AMA and liver function tests should be recommended to other family members for the early detection and management of this condition, especially for female relatives,” the investigators wrote.
Find the full case report in the World Journal of Gastroenterology (doi: 10.3748/wjg.v23.i39.7191).
A case report involving a family with four sisters with primary biliary cholangitis (PBC) suggests that there may be a maternal inheritance of susceptibility, according to Saeam Shin, MD, and associates at Hallym University in Seoul, South Korea.
In the first case, a 56-year-old woman was diagnosed with PBC, and afterwards, her three sisters, her brother, and her half-sister born to a different mother were evaluated for PBC as well. The second and fourth sisters showed no symptoms, but they were antimitochondrial-antibody (AMA) positive and were diagnosed with PBC. The third sister had been admitted to a different hospital for acute hepatitis of unknown origin – after receiving a positive AMA test, she also was diagnosed with PBC.
The brother and half-sister evaluated for PBC showed no symptoms and had negative AMA tests. The four sisters diagnosed showed good response to ursodeoxycholic acid in liver biochemistry tests and have continued on that medication without complication.
“If one patient is diagnosed with PBC, screening with AMA and liver function tests should be recommended to other family members for the early detection and management of this condition, especially for female relatives,” the investigators wrote.
Find the full case report in the World Journal of Gastroenterology (doi: 10.3748/wjg.v23.i39.7191).
FROM THE WORLD JOURNAL OF GASTROENTEROLOGY
Does Anyone Really Understand Nutrition Labels?
In 1990, nutrition labeling—that handy chart that gives us the information we need to make healthy choices—was added to nearly all packaged foods. But according to researchers from the FDA, Tufts University, and the National Cancer Institute, many people lack the health literacy to understand the information and use it as intended.
The researchers analyzed data on 3,185 U.S. adults from the Health Information National Trends Survey, conducted in 2013. Participants were asked to view an ice-cream nutrition label and answer 4 questions that tested their ability to apply basic arithmetic and understanding of percentages to interpret the label. They also reported their intake of sugar-sweetened soft drinks, fruits, and vegetables.
About one-quarter of the participants could not determine the calorie content of the full ice-cream container; 42% could not estimate the effect on daily calorie intake of foregoing 1 serving; 41% could not calculate the percentage daily value of calories in a single serving; and 21% could not estimate the number of servings equal to 60 g of carbohydrates.
Higher scores of label understanding were associated with consuming more vegetables and fewer sugar-sweetened drinks. After adjusting for demographic factors, only the link with soft drinks remained significant.
Across all educational levels, people had the most trouble with the questions about health recommendations and daily value. As in other studies, low educational attainment was associated with poor understanding of nutrition labels. More than one-third of participants with less than a high school diploma could not correctly answer any of the questions. Less than 9% could answer all 4 correctly. However, only 54% of participants with a 4-year college degree could answer all the questions correctly.
One obvious way to improve things, the researchers suggest, is to make the nutrition label easier to use. They note that the FDA tried to do this in 2016, in addition to reflecting current nutrition science and public health research. For instance, certain label elements, like calories and serving size, are now larger and in a bold font. Serving sizes have been updated to more accurately reflect the amount of food and drink people usually consume. To help consumers better understand serving size, 2 columns are used for foods that can be eaten in 1 or multiple sittings, such as a bag of potato chips, so people will better grasp how many calories they consume in 1 sitting.
Still, understanding nutrition labels is not the same as using the nutrition information for selecting food, the researchers point out. Participants who answered all 4 questions correctly might not necessarily use the labels when buying food.
In 1990, nutrition labeling—that handy chart that gives us the information we need to make healthy choices—was added to nearly all packaged foods. But according to researchers from the FDA, Tufts University, and the National Cancer Institute, many people lack the health literacy to understand the information and use it as intended.
The researchers analyzed data on 3,185 U.S. adults from the Health Information National Trends Survey, conducted in 2013. Participants were asked to view an ice-cream nutrition label and answer 4 questions that tested their ability to apply basic arithmetic and understanding of percentages to interpret the label. They also reported their intake of sugar-sweetened soft drinks, fruits, and vegetables.
About one-quarter of the participants could not determine the calorie content of the full ice-cream container; 42% could not estimate the effect on daily calorie intake of foregoing 1 serving; 41% could not calculate the percentage daily value of calories in a single serving; and 21% could not estimate the number of servings equal to 60 g of carbohydrates.
Higher scores of label understanding were associated with consuming more vegetables and fewer sugar-sweetened drinks. After adjusting for demographic factors, only the link with soft drinks remained significant.
Across all educational levels, people had the most trouble with the questions about health recommendations and daily value. As in other studies, low educational attainment was associated with poor understanding of nutrition labels. More than one-third of participants with less than a high school diploma could not correctly answer any of the questions. Less than 9% could answer all 4 correctly. However, only 54% of participants with a 4-year college degree could answer all the questions correctly.
One obvious way to improve things, the researchers suggest, is to make the nutrition label easier to use. They note that the FDA tried to do this in 2016, in addition to reflecting current nutrition science and public health research. For instance, certain label elements, like calories and serving size, are now larger and in a bold font. Serving sizes have been updated to more accurately reflect the amount of food and drink people usually consume. To help consumers better understand serving size, 2 columns are used for foods that can be eaten in 1 or multiple sittings, such as a bag of potato chips, so people will better grasp how many calories they consume in 1 sitting.
Still, understanding nutrition labels is not the same as using the nutrition information for selecting food, the researchers point out. Participants who answered all 4 questions correctly might not necessarily use the labels when buying food.
In 1990, nutrition labeling—that handy chart that gives us the information we need to make healthy choices—was added to nearly all packaged foods. But according to researchers from the FDA, Tufts University, and the National Cancer Institute, many people lack the health literacy to understand the information and use it as intended.
The researchers analyzed data on 3,185 U.S. adults from the Health Information National Trends Survey, conducted in 2013. Participants were asked to view an ice-cream nutrition label and answer 4 questions that tested their ability to apply basic arithmetic and understanding of percentages to interpret the label. They also reported their intake of sugar-sweetened soft drinks, fruits, and vegetables.
About one-quarter of the participants could not determine the calorie content of the full ice-cream container; 42% could not estimate the effect on daily calorie intake of foregoing 1 serving; 41% could not calculate the percentage daily value of calories in a single serving; and 21% could not estimate the number of servings equal to 60 g of carbohydrates.
Higher scores of label understanding were associated with consuming more vegetables and fewer sugar-sweetened drinks. After adjusting for demographic factors, only the link with soft drinks remained significant.
Across all educational levels, people had the most trouble with the questions about health recommendations and daily value. As in other studies, low educational attainment was associated with poor understanding of nutrition labels. More than one-third of participants with less than a high school diploma could not correctly answer any of the questions. Less than 9% could answer all 4 correctly. However, only 54% of participants with a 4-year college degree could answer all the questions correctly.
One obvious way to improve things, the researchers suggest, is to make the nutrition label easier to use. They note that the FDA tried to do this in 2016, in addition to reflecting current nutrition science and public health research. For instance, certain label elements, like calories and serving size, are now larger and in a bold font. Serving sizes have been updated to more accurately reflect the amount of food and drink people usually consume. To help consumers better understand serving size, 2 columns are used for foods that can be eaten in 1 or multiple sittings, such as a bag of potato chips, so people will better grasp how many calories they consume in 1 sitting.
Still, understanding nutrition labels is not the same as using the nutrition information for selecting food, the researchers point out. Participants who answered all 4 questions correctly might not necessarily use the labels when buying food.
FDA approves first treatment for ECD
The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.
Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.
The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.
Now, vemurafenib is the first FDA-approved treatment for ECD.
The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.
“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”
The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.
VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.
In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.
The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain. 
The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.
Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.
The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.
Now, vemurafenib is the first FDA-approved treatment for ECD.
The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.
“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”
The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.
VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.
In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.
The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.
The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.
Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.
The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.
Now, vemurafenib is the first FDA-approved treatment for ECD.
The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.
“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”
The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.
VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.
In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.
The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.
