Monthly lab testing for isotretinoin? No need, expert says

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WAILEA, HAWAII– Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.

She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.

Bruce Jancin/Frontline Medical News
Dr. Julie C. Harper
“I used to check labs monthly, too, but I’ve changed my practice as a result of this study. I perform a lipid and hepatic panel at baseline and after 2 months of isotretinoin therapy, and if those numbers are okay I don’t check them again,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.

The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.

“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.

Similarly, there was no substantial late effect of isotretinoin on total cholesterol.

The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.

Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).

“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.

“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”

In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.

The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.

Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.

“We’re saving money, too,” she noted.

Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).

She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.
 

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WAILEA, HAWAII– Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.

She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.

Bruce Jancin/Frontline Medical News
Dr. Julie C. Harper
“I used to check labs monthly, too, but I’ve changed my practice as a result of this study. I perform a lipid and hepatic panel at baseline and after 2 months of isotretinoin therapy, and if those numbers are okay I don’t check them again,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.

The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.

“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.

Similarly, there was no substantial late effect of isotretinoin on total cholesterol.

The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.

Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).

“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.

“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”

In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.

The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.

Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.

“We’re saving money, too,” she noted.

Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).

She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.
 

 

WAILEA, HAWAII– Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.

She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.

Bruce Jancin/Frontline Medical News
Dr. Julie C. Harper
“I used to check labs monthly, too, but I’ve changed my practice as a result of this study. I perform a lipid and hepatic panel at baseline and after 2 months of isotretinoin therapy, and if those numbers are okay I don’t check them again,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.

The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.

“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.

Similarly, there was no substantial late effect of isotretinoin on total cholesterol.

The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.

Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).

“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.

“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”

In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.

The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.

Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.

“We’re saving money, too,” she noted.

Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).

She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.
 

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STAS predictive for lung SCC recurrence

Refining prognosis with careful pathological examination
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First described in 2015, tumor spread through air spaces is a recently recognized form of invasion in lung carcinoma, but it has not been well described in lung squamous cell carcinoma. However, a study out of Memorial Sloan-Kettering Cancer Center reports spread through air spaces (STAS) is one of the most significant histologic findings in lung squamous cell carcinoma (SCC).

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STAS (spread through air spaces) has emerged as a harbinger of poor clinical behavior in adenocarcinoma of the lung. In this new manuscript, a team from Memorial Sloan-Kettering Cancer Center demonstrates that this phenomenon is evident in squamous cell cancer of the lung as well.

Dr. Sai Yendamuri
A few important take-home messages are worthy of particular note in this manuscript. The first is that STAS is fairly common, present in one-third of all patients with squamous cell cancer. The second is that STAS is correlated with other known indicators of aggressive behavior such as stage, vascular and lymphatic invasion, and a high Ki-67 labeling index. The third is that STAS is not restricted to one particular histological subtype of squamous cell cancer. The fourth is that STAS is predictive of lung cancer–related recurrence and death, independent of other prognostic factors.

While the study needs to be replicated in other datasets, it demonstrates the power of careful pathologic examination in predicting tumor biology. The age old concept deserves renewed emphasis in the current era of ‘Omics’ of various kinds.

Sai Yendamuri, MD, is professor and chair of the department of thoracic surgery at Roswell Park Cancer Institute in Buffalo, N.Y., and is an associate medical editor for Thoracic Surgery News. He has no relevant disclosures.

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STAS (spread through air spaces) has emerged as a harbinger of poor clinical behavior in adenocarcinoma of the lung. In this new manuscript, a team from Memorial Sloan-Kettering Cancer Center demonstrates that this phenomenon is evident in squamous cell cancer of the lung as well.

Dr. Sai Yendamuri
A few important take-home messages are worthy of particular note in this manuscript. The first is that STAS is fairly common, present in one-third of all patients with squamous cell cancer. The second is that STAS is correlated with other known indicators of aggressive behavior such as stage, vascular and lymphatic invasion, and a high Ki-67 labeling index. The third is that STAS is not restricted to one particular histological subtype of squamous cell cancer. The fourth is that STAS is predictive of lung cancer–related recurrence and death, independent of other prognostic factors.

While the study needs to be replicated in other datasets, it demonstrates the power of careful pathologic examination in predicting tumor biology. The age old concept deserves renewed emphasis in the current era of ‘Omics’ of various kinds.

Sai Yendamuri, MD, is professor and chair of the department of thoracic surgery at Roswell Park Cancer Institute in Buffalo, N.Y., and is an associate medical editor for Thoracic Surgery News. He has no relevant disclosures.

Body

 

STAS (spread through air spaces) has emerged as a harbinger of poor clinical behavior in adenocarcinoma of the lung. In this new manuscript, a team from Memorial Sloan-Kettering Cancer Center demonstrates that this phenomenon is evident in squamous cell cancer of the lung as well.

Dr. Sai Yendamuri
A few important take-home messages are worthy of particular note in this manuscript. The first is that STAS is fairly common, present in one-third of all patients with squamous cell cancer. The second is that STAS is correlated with other known indicators of aggressive behavior such as stage, vascular and lymphatic invasion, and a high Ki-67 labeling index. The third is that STAS is not restricted to one particular histological subtype of squamous cell cancer. The fourth is that STAS is predictive of lung cancer–related recurrence and death, independent of other prognostic factors.

While the study needs to be replicated in other datasets, it demonstrates the power of careful pathologic examination in predicting tumor biology. The age old concept deserves renewed emphasis in the current era of ‘Omics’ of various kinds.

Sai Yendamuri, MD, is professor and chair of the department of thoracic surgery at Roswell Park Cancer Institute in Buffalo, N.Y., and is an associate medical editor for Thoracic Surgery News. He has no relevant disclosures.

Title
Refining prognosis with careful pathological examination
Refining prognosis with careful pathological examination

 

First described in 2015, tumor spread through air spaces is a recently recognized form of invasion in lung carcinoma, but it has not been well described in lung squamous cell carcinoma. However, a study out of Memorial Sloan-Kettering Cancer Center reports spread through air spaces (STAS) is one of the most significant histologic findings in lung squamous cell carcinoma (SCC).

 

First described in 2015, tumor spread through air spaces is a recently recognized form of invasion in lung carcinoma, but it has not been well described in lung squamous cell carcinoma. However, a study out of Memorial Sloan-Kettering Cancer Center reports spread through air spaces (STAS) is one of the most significant histologic findings in lung squamous cell carcinoma (SCC).

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Key clinical point: Spread through air spaces (STAS) is a prognostic histologic finding in lung squamous cell carcinoma.

Major finding: STAS was observed in 30% of patients and frequency increased with age.

Data source: Retrospective analysis of 445 resections for solitary stage I-III lung squamous cell carcinoma at Memorial Sloan-Kettering Cancer Center between 1999 and 2009.

Disclosure: Dr. Lu and coauthors reported having no relevant financial disclosures.

Morris Levin, MD

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HCV testing stagnant among baby boomers

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Despite the urging of the United States Preventive Services Task Force and other organizations in 2013, the percentage of baby boomers who underwent testing for hepatitis C (HCV) infection had barely changed 2 years later – from 12.3% in 2013 to 13.8% in 2015.

Jarun011/Thinkstock
New guidelines often take time to get adopted by public health and medical communities, but the authors expected some increase. “But there wasn’t. It just remained pretty low. It was a little bit surprising,” said study coauthor Stacey Fedewa, PhD, strategic director of risk factors and screening surveillance at the American Cancer Society.

Other reactions were more forceful. “Kind of pathetic, isn’t it?” said John D. Scott, MD, assistant director of the Hepatitis and Liver Clinic at Harborview Medical Center, and an associate professor of medicine at the University of Washington, Seattle.

The researchers analyzed 2013 and 2015 data from the National Health Interview Survey, which included records for 21,827 baby boomers with HCV testing data.

The slight increase overall of 12.3% to 13.8% was small but also statistically significant (P = .013). Some populations fared better: Compared with the privately insured, those with Medicare plus Medicaid were more likely to have been tested (prevalence ratio, 1.83; 95% confidence interval, 1.32-2.53), as were those only on Medicaid (PR, 1.35; 95% CI, 1.04-1.76), and those with military insurance (PR, 1.62; 95% CI, 1.16-2.26).

The study could be subject to recall bias, since it relied on participants’ self-reports.

The authors speculate that the higher prevalence of testing in those with military insurance may reflect efforts by the Veterans Health Administration to reduce the high prevalence of HCV-associated disease among veterans.

It’s entirely possible to increase testing rates, according to Dr. Scott, who has a grant from the Centers for Disease Control and Prevention to study ways to increase uptake. “Probably the easiest thing to do is just incorporate this information into your electronic medical record and make it part of your alerts and standard preventative practices. Try to automate a lot of this rather than remind a very busy primary care doctor of all the things they have to do,” he said.

For example, one strategy that Seattle’s King County has employed is to automatically notify the testing laboratory if an antibody test is positive. “The lab knows to keep that blood and run a second (nucleic acid) test without the patient having to come back. That has helped to get our confirmatory rates up,” said Dr. Scott.

More broadly, the importance of testing needs to be emphasized, according to Paul J. Thuluvath, MD, medical director at the Institute of Digestive Health and Liver Disease at Mercy Medical Center, Baltimore, and a professor of medicine and surgery at the University of Maryland. “We need everybody to buy into this: the primary care physicians, internists, and gynecologists. If they are not convinced of the importance of this, it’s not going to happen. And I don’t think many primary care physicians and internists are convinced yet,” he said.

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Despite the urging of the United States Preventive Services Task Force and other organizations in 2013, the percentage of baby boomers who underwent testing for hepatitis C (HCV) infection had barely changed 2 years later – from 12.3% in 2013 to 13.8% in 2015.

Jarun011/Thinkstock
New guidelines often take time to get adopted by public health and medical communities, but the authors expected some increase. “But there wasn’t. It just remained pretty low. It was a little bit surprising,” said study coauthor Stacey Fedewa, PhD, strategic director of risk factors and screening surveillance at the American Cancer Society.

Other reactions were more forceful. “Kind of pathetic, isn’t it?” said John D. Scott, MD, assistant director of the Hepatitis and Liver Clinic at Harborview Medical Center, and an associate professor of medicine at the University of Washington, Seattle.

The researchers analyzed 2013 and 2015 data from the National Health Interview Survey, which included records for 21,827 baby boomers with HCV testing data.

The slight increase overall of 12.3% to 13.8% was small but also statistically significant (P = .013). Some populations fared better: Compared with the privately insured, those with Medicare plus Medicaid were more likely to have been tested (prevalence ratio, 1.83; 95% confidence interval, 1.32-2.53), as were those only on Medicaid (PR, 1.35; 95% CI, 1.04-1.76), and those with military insurance (PR, 1.62; 95% CI, 1.16-2.26).

The study could be subject to recall bias, since it relied on participants’ self-reports.

The authors speculate that the higher prevalence of testing in those with military insurance may reflect efforts by the Veterans Health Administration to reduce the high prevalence of HCV-associated disease among veterans.

It’s entirely possible to increase testing rates, according to Dr. Scott, who has a grant from the Centers for Disease Control and Prevention to study ways to increase uptake. “Probably the easiest thing to do is just incorporate this information into your electronic medical record and make it part of your alerts and standard preventative practices. Try to automate a lot of this rather than remind a very busy primary care doctor of all the things they have to do,” he said.

For example, one strategy that Seattle’s King County has employed is to automatically notify the testing laboratory if an antibody test is positive. “The lab knows to keep that blood and run a second (nucleic acid) test without the patient having to come back. That has helped to get our confirmatory rates up,” said Dr. Scott.

More broadly, the importance of testing needs to be emphasized, according to Paul J. Thuluvath, MD, medical director at the Institute of Digestive Health and Liver Disease at Mercy Medical Center, Baltimore, and a professor of medicine and surgery at the University of Maryland. “We need everybody to buy into this: the primary care physicians, internists, and gynecologists. If they are not convinced of the importance of this, it’s not going to happen. And I don’t think many primary care physicians and internists are convinced yet,” he said.

 

Despite the urging of the United States Preventive Services Task Force and other organizations in 2013, the percentage of baby boomers who underwent testing for hepatitis C (HCV) infection had barely changed 2 years later – from 12.3% in 2013 to 13.8% in 2015.

Jarun011/Thinkstock
New guidelines often take time to get adopted by public health and medical communities, but the authors expected some increase. “But there wasn’t. It just remained pretty low. It was a little bit surprising,” said study coauthor Stacey Fedewa, PhD, strategic director of risk factors and screening surveillance at the American Cancer Society.

Other reactions were more forceful. “Kind of pathetic, isn’t it?” said John D. Scott, MD, assistant director of the Hepatitis and Liver Clinic at Harborview Medical Center, and an associate professor of medicine at the University of Washington, Seattle.

The researchers analyzed 2013 and 2015 data from the National Health Interview Survey, which included records for 21,827 baby boomers with HCV testing data.

The slight increase overall of 12.3% to 13.8% was small but also statistically significant (P = .013). Some populations fared better: Compared with the privately insured, those with Medicare plus Medicaid were more likely to have been tested (prevalence ratio, 1.83; 95% confidence interval, 1.32-2.53), as were those only on Medicaid (PR, 1.35; 95% CI, 1.04-1.76), and those with military insurance (PR, 1.62; 95% CI, 1.16-2.26).

The study could be subject to recall bias, since it relied on participants’ self-reports.

The authors speculate that the higher prevalence of testing in those with military insurance may reflect efforts by the Veterans Health Administration to reduce the high prevalence of HCV-associated disease among veterans.

It’s entirely possible to increase testing rates, according to Dr. Scott, who has a grant from the Centers for Disease Control and Prevention to study ways to increase uptake. “Probably the easiest thing to do is just incorporate this information into your electronic medical record and make it part of your alerts and standard preventative practices. Try to automate a lot of this rather than remind a very busy primary care doctor of all the things they have to do,” he said.

For example, one strategy that Seattle’s King County has employed is to automatically notify the testing laboratory if an antibody test is positive. “The lab knows to keep that blood and run a second (nucleic acid) test without the patient having to come back. That has helped to get our confirmatory rates up,” said Dr. Scott.

More broadly, the importance of testing needs to be emphasized, according to Paul J. Thuluvath, MD, medical director at the Institute of Digestive Health and Liver Disease at Mercy Medical Center, Baltimore, and a professor of medicine and surgery at the University of Maryland. “We need everybody to buy into this: the primary care physicians, internists, and gynecologists. If they are not convinced of the importance of this, it’s not going to happen. And I don’t think many primary care physicians and internists are convinced yet,” he said.

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Immunotherapy boosts OS from metastatic cervical cancer in early trial

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– An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.

Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.

Amy Karon/Frontline Medical News
Dr. Charles Leath
Patients with persistent or recurrent metastatic cervical cancers have very few treatment options. Since 1998, more than 20 phase II trials have sought to fill this gap, and none has yielded a 12-month OS above 30%, noted Dr. Leath, who is at the University of Alabama at Birmingham. Based on the premise that Listeria monocytogenes can be genetically modified to express fusion proteins with antigens specific to certain cancers, researchers bioengineered axalimogene filolisbac to target cervical cancer by secreting a human papillomavirus–16 E7 protein fused to a truncated fragment of listeriolysin O. Treatment aims to induce antitumor immunity and overcome immune tolerance in the tumor microenvironment, said Dr. Leath.

In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.

Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.

Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.

The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.

The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
 

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– An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.

Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.

Amy Karon/Frontline Medical News
Dr. Charles Leath
Patients with persistent or recurrent metastatic cervical cancers have very few treatment options. Since 1998, more than 20 phase II trials have sought to fill this gap, and none has yielded a 12-month OS above 30%, noted Dr. Leath, who is at the University of Alabama at Birmingham. Based on the premise that Listeria monocytogenes can be genetically modified to express fusion proteins with antigens specific to certain cancers, researchers bioengineered axalimogene filolisbac to target cervical cancer by secreting a human papillomavirus–16 E7 protein fused to a truncated fragment of listeriolysin O. Treatment aims to induce antitumor immunity and overcome immune tolerance in the tumor microenvironment, said Dr. Leath.

In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.

Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.

Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.

The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.

The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
 

 

– An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.

Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.

Amy Karon/Frontline Medical News
Dr. Charles Leath
Patients with persistent or recurrent metastatic cervical cancers have very few treatment options. Since 1998, more than 20 phase II trials have sought to fill this gap, and none has yielded a 12-month OS above 30%, noted Dr. Leath, who is at the University of Alabama at Birmingham. Based on the premise that Listeria monocytogenes can be genetically modified to express fusion proteins with antigens specific to certain cancers, researchers bioengineered axalimogene filolisbac to target cervical cancer by secreting a human papillomavirus–16 E7 protein fused to a truncated fragment of listeriolysin O. Treatment aims to induce antitumor immunity and overcome immune tolerance in the tumor microenvironment, said Dr. Leath.

In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.

Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.

Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.

The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.

The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
 

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Key clinical point. Treatment with axalimogene filolisbac led to a 52% improvement in overall survival, compared with pooled historical data, in previously treated patients with metastatic cervical cancer.

Major finding: Twelve-month overall survival was 38%, significantly greater than the modeled prediction of 25% had patients gone untreated (P = .02).

Data source: A multicenter phase II trial of 50 patients with previously treated metastatic cervical cancer.

Disclosures: The study was supported by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and honoraria or reimbursements from Celsion and Genentech/Roche.

Steven Baskin, PhD

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New Trump travel order could disrupt meetings, trainees

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President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.

The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.

The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.

The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.

“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”

The leadership of Digestive Disease Week® (DDW) believes that the recent executive order banning travel of foreign nationals and refugees from seven countries to the U.S. will stifle discussion among members of the scientific community. Presentations and meetings that occur during DDW allow physicians and scientists from around the world to learn about and discuss cutting-edge scientific research and create partnerships that often lead to innovations in identifying, screening, and treating digestive disorders, as well as improving patient care.

The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”

When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.

A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.

The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

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President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.

The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.

The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.

The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.

“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”

The leadership of Digestive Disease Week® (DDW) believes that the recent executive order banning travel of foreign nationals and refugees from seven countries to the U.S. will stifle discussion among members of the scientific community. Presentations and meetings that occur during DDW allow physicians and scientists from around the world to learn about and discuss cutting-edge scientific research and create partnerships that often lead to innovations in identifying, screening, and treating digestive disorders, as well as improving patient care.

The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”

When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.

A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.

The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

 

President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.

The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.

The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.

The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.

“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”

The leadership of Digestive Disease Week® (DDW) believes that the recent executive order banning travel of foreign nationals and refugees from seven countries to the U.S. will stifle discussion among members of the scientific community. Presentations and meetings that occur during DDW allow physicians and scientists from around the world to learn about and discuss cutting-edge scientific research and create partnerships that often lead to innovations in identifying, screening, and treating digestive disorders, as well as improving patient care.

The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”

When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.

A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.

The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

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FDA grants Hodgkin lymphoma indication for pembrolizumab

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Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

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Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

 

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

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Common gut yeast may exacerbate IBD

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A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.

 

While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.

In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).

Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.

To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”

Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
 

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A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.

 

While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.

In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).

Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.

To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”

Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
 

 

A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.

 

While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.

In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).

Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.

To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”

Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
 

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Key clinical point: A yeast strain common in foods may increase gut uric acid levels, promoting colon damage in IBD.

Major finding: Sterile mice inoculated with S. cerevisiae and treated to induce colitis had more tissue damage than untreated mice or those treated with another type of yeast.

Data source: An experimental study on mice inoculated with one of two yeasts, then treated to induce colitislike symptoms.

Disclosures: Study authors had multiple sources of individual grant funding but no commercial conflicts of interest.

Can better operations improve CABG in women?

Consider postoperative risk factors
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Worse outcomes after cardiovascular arterial bypass grafting (CABG) in women have been attributed to a number of clinical and nonclinical factors: older age, delayed diagnosis and treatment, more comorbidities, smaller body size, underuse of arterial grafts, and referral bias. However, a team of Cleveland Clinic researchers reported that women were less likely than men to have bilateral–internal thoracic artery (ITA) grafting and complete revascularization, both of which are linked to better long-term survival.

Body

 

As with other long-term analyses, the answer in this study “is in the shadows as opposed to the spotlight,” George L. Hicks Jr., MD, said in his invited commentary (J Thorac Cardiovasc Surg. 2017;153[3]:580-1).

Dr. Hicks of the University of Rochester (N.Y.) noted key limitations of the study: use of all-cause mortality, substandard use of bilateral– or single–internal thoracic artery grafting, little data about postdischarge cholesterol levels, diabetes incidence, or blood pressure, among others. However, “the authors raise the banner for the continued need for increased use of arterial revascularization with the eventual hope that the Arterial Revascularization Trial will reinforce the survival benefits manifested by that strategy,” he said.

Dr. George L. Hicks Jr.
Dr. Hicks invoked the besseller, “Men Are From Mars and Women From Venus.” “If men are truly from Mars and different from the women of Venus, it behooves all practitioners to aggressively monitor and treat women after menopause for the potential – if not inevitable – onset of cardiovascular problems, hypertension, hyperlipidemia, diabetes, and stroke,” Dr. Hicks said.

Reducing risks and not changing the type of operation will even out the differences in postoperative survival between genders, he indicated. “Furthermore, the extension of similar therapies – for example, [bilateral–internal thoracic artery] or all-arterial grafting and improved long-term risk modification in both men and women – may improve the inequality but not eliminate the differences until we know that both men and women come from the same planet,” he said.

Dr. Hicks reported having no relevant financial relationships to disclose.

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As with other long-term analyses, the answer in this study “is in the shadows as opposed to the spotlight,” George L. Hicks Jr., MD, said in his invited commentary (J Thorac Cardiovasc Surg. 2017;153[3]:580-1).

Dr. Hicks of the University of Rochester (N.Y.) noted key limitations of the study: use of all-cause mortality, substandard use of bilateral– or single–internal thoracic artery grafting, little data about postdischarge cholesterol levels, diabetes incidence, or blood pressure, among others. However, “the authors raise the banner for the continued need for increased use of arterial revascularization with the eventual hope that the Arterial Revascularization Trial will reinforce the survival benefits manifested by that strategy,” he said.

Dr. George L. Hicks Jr.
Dr. Hicks invoked the besseller, “Men Are From Mars and Women From Venus.” “If men are truly from Mars and different from the women of Venus, it behooves all practitioners to aggressively monitor and treat women after menopause for the potential – if not inevitable – onset of cardiovascular problems, hypertension, hyperlipidemia, diabetes, and stroke,” Dr. Hicks said.

Reducing risks and not changing the type of operation will even out the differences in postoperative survival between genders, he indicated. “Furthermore, the extension of similar therapies – for example, [bilateral–internal thoracic artery] or all-arterial grafting and improved long-term risk modification in both men and women – may improve the inequality but not eliminate the differences until we know that both men and women come from the same planet,” he said.

Dr. Hicks reported having no relevant financial relationships to disclose.

Body

 

As with other long-term analyses, the answer in this study “is in the shadows as opposed to the spotlight,” George L. Hicks Jr., MD, said in his invited commentary (J Thorac Cardiovasc Surg. 2017;153[3]:580-1).

Dr. Hicks of the University of Rochester (N.Y.) noted key limitations of the study: use of all-cause mortality, substandard use of bilateral– or single–internal thoracic artery grafting, little data about postdischarge cholesterol levels, diabetes incidence, or blood pressure, among others. However, “the authors raise the banner for the continued need for increased use of arterial revascularization with the eventual hope that the Arterial Revascularization Trial will reinforce the survival benefits manifested by that strategy,” he said.

Dr. George L. Hicks Jr.
Dr. Hicks invoked the besseller, “Men Are From Mars and Women From Venus.” “If men are truly from Mars and different from the women of Venus, it behooves all practitioners to aggressively monitor and treat women after menopause for the potential – if not inevitable – onset of cardiovascular problems, hypertension, hyperlipidemia, diabetes, and stroke,” Dr. Hicks said.

Reducing risks and not changing the type of operation will even out the differences in postoperative survival between genders, he indicated. “Furthermore, the extension of similar therapies – for example, [bilateral–internal thoracic artery] or all-arterial grafting and improved long-term risk modification in both men and women – may improve the inequality but not eliminate the differences until we know that both men and women come from the same planet,” he said.

Dr. Hicks reported having no relevant financial relationships to disclose.

Title
Consider postoperative risk factors
Consider postoperative risk factors

 

Worse outcomes after cardiovascular arterial bypass grafting (CABG) in women have been attributed to a number of clinical and nonclinical factors: older age, delayed diagnosis and treatment, more comorbidities, smaller body size, underuse of arterial grafts, and referral bias. However, a team of Cleveland Clinic researchers reported that women were less likely than men to have bilateral–internal thoracic artery (ITA) grafting and complete revascularization, both of which are linked to better long-term survival.

 

Worse outcomes after cardiovascular arterial bypass grafting (CABG) in women have been attributed to a number of clinical and nonclinical factors: older age, delayed diagnosis and treatment, more comorbidities, smaller body size, underuse of arterial grafts, and referral bias. However, a team of Cleveland Clinic researchers reported that women were less likely than men to have bilateral–internal thoracic artery (ITA) grafting and complete revascularization, both of which are linked to better long-term survival.

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FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY

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Key clinical point: Survival rates after CABG are worse for women than for men.

Major finding: In both men and women, complete revascularization and use of bilateral-ITA grafting achieve better long-term survival than incomplete revascularization and single-ITA grafting.

Data source: Analysis of 57,943 adults who had primary isolated CABG from 1972 to 2011 at Cleveland Clinic.

Disclosure: Coauthor Ellen Mayer Sabik, MD, is a principal investigator for Abbott Laboratories and is on the scientific advisory board of Medtronic. Dr. Attia and all other coauthors reported having no relevant financial disclosures.