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STAS predictive for lung SCC recurrence
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).
In multivariable models for any recurrence and lung cancer–specific death, the researchers found that STAS was a significant independent predictor for both outcomes (P = .034 and .016, respectively).
“We found that STAS in lung SCC was associated with p-stage, lymphatic and vascular invasion, necrosis, larger nuclear diameter, increased mitoses and high Ki-67 labeling index,” wrote lead author Shaohua Lu, MD, and coauthors (J Thorac Oncol. 2017 Feb;12[2]:223-34). Their findings are based on an analysis of 445 patients who had resection for stage I-III SCC over a 10-year period ending in 2009.
The Sloan-Kettering Group previously reported that STAS was a predictor of recurrence in stage I lung adenocarcinoma patients who had a limited resection (J Thorac Oncol. 2015;10[5]:806-14), and others reported STAS was a clinically significant finding in the disease. In the latest study, Dr. Lu and colleagues set out to determine if STAS is associated with tumor aggressiveness in lung SCC by using a large cohort of patients who had lung SCC resection. The lung resections they studied are from the aforementioned 2015 study that used immunohistochemistry to confirm squamous differentiation in otherwise poorly differentiated tumors.
Two pathologists reviewed tumor slides and used Ki-67 staining to confirm squamous differentiation. The study population comprised 98% former smokers and the median age was 71.3; 76% (336) were older than 65.
Dr. Lu and colleagues noted how STAS in lung SCC differs from its presentation in lung adenocarcinoma. “In contrast to lung adenocarcinoma, in which STAS can manifest as micropapillary clusters, solid nests or single cells, all STAS lesions in lung SCCs consist of solid tumor cell nests,” they wrote.
They found that STAS was associated with a higher risk of recurrence in SCC patients who had lobectomy, but not sublobar resection, whereas in patients with lung adenocarcinoma STAS was associated with a high risk of recurrence if they had sublobar resection.
The study observed STAS in 132 patients (30%). With a median follow-up of 3.4 years, 61% (273) of all patients died in that time. STAS tumors were more aggressive in nature than were non-STAS tumors. Pathologic features strongly associated with STAS were lymphatic invasion (40% for STAS vs. 19% for non-STAS patients); vascular invasion (36% vs. 22%); larger tumor size (median 4 cm vs. 3 cm); higher Ki-67 labeling index (32% vs. 13%); and higher tumor stage (23% with p-stage I, 35% p-stage II, and 43% p-stage III), all significant differences. Patients with STAS also had a higher 5-year cumulative incidence of any recurrence (39% vs. 26%) and lung cancer-specific death (30% vs. 14%), both significant differences.
STAS has an “insidious pattern of tumor invasion” that can be difficult for pathologists to detect and requires the gathering of specimens that include the adjacent lung parenchyma, Dr. Lu and colleagues said. They also dispelled the myth that STAS is an ex vivo artifact. “STAS is morphologically different from tissue floaters and contaminant or extraneous tissues that can lead to diagnostic errors,” they said.
And while the study showed that STAS is an independent predictor of recurrence and cancer-specific death, it was not predictive of overall survival – perhaps because most of the study population was over age 65 and were more likely to die from other causes rather than lung cancer. “We found a strong correlation between STAS and high-grade morphologic patterns such as nuclear size, nuclear atypia, mitotic count and Ki-67 labeling index, suggesting that STAS is associated with tumor proliferation,” Dr. Lu and coauthors said.
“Because we found STAS to show greater prognostic significance than lymphatic vascular, and visceral pleural invasion, all of which are histologic features recommended to be recorded in pathology reports for lung cancer specimens, in the future, STAS may be appropriate to add to this list,” the researchers noted.
Dr. Lu and coauthors had no financial relationships to disclose.
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.
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.
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.
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.
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.
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.
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).
In multivariable models for any recurrence and lung cancer–specific death, the researchers found that STAS was a significant independent predictor for both outcomes (P = .034 and .016, respectively).
“We found that STAS in lung SCC was associated with p-stage, lymphatic and vascular invasion, necrosis, larger nuclear diameter, increased mitoses and high Ki-67 labeling index,” wrote lead author Shaohua Lu, MD, and coauthors (J Thorac Oncol. 2017 Feb;12[2]:223-34). Their findings are based on an analysis of 445 patients who had resection for stage I-III SCC over a 10-year period ending in 2009.
The Sloan-Kettering Group previously reported that STAS was a predictor of recurrence in stage I lung adenocarcinoma patients who had a limited resection (J Thorac Oncol. 2015;10[5]:806-14), and others reported STAS was a clinically significant finding in the disease. In the latest study, Dr. Lu and colleagues set out to determine if STAS is associated with tumor aggressiveness in lung SCC by using a large cohort of patients who had lung SCC resection. The lung resections they studied are from the aforementioned 2015 study that used immunohistochemistry to confirm squamous differentiation in otherwise poorly differentiated tumors.
Two pathologists reviewed tumor slides and used Ki-67 staining to confirm squamous differentiation. The study population comprised 98% former smokers and the median age was 71.3; 76% (336) were older than 65.
Dr. Lu and colleagues noted how STAS in lung SCC differs from its presentation in lung adenocarcinoma. “In contrast to lung adenocarcinoma, in which STAS can manifest as micropapillary clusters, solid nests or single cells, all STAS lesions in lung SCCs consist of solid tumor cell nests,” they wrote.
They found that STAS was associated with a higher risk of recurrence in SCC patients who had lobectomy, but not sublobar resection, whereas in patients with lung adenocarcinoma STAS was associated with a high risk of recurrence if they had sublobar resection.
The study observed STAS in 132 patients (30%). With a median follow-up of 3.4 years, 61% (273) of all patients died in that time. STAS tumors were more aggressive in nature than were non-STAS tumors. Pathologic features strongly associated with STAS were lymphatic invasion (40% for STAS vs. 19% for non-STAS patients); vascular invasion (36% vs. 22%); larger tumor size (median 4 cm vs. 3 cm); higher Ki-67 labeling index (32% vs. 13%); and higher tumor stage (23% with p-stage I, 35% p-stage II, and 43% p-stage III), all significant differences. Patients with STAS also had a higher 5-year cumulative incidence of any recurrence (39% vs. 26%) and lung cancer-specific death (30% vs. 14%), both significant differences.
STAS has an “insidious pattern of tumor invasion” that can be difficult for pathologists to detect and requires the gathering of specimens that include the adjacent lung parenchyma, Dr. Lu and colleagues said. They also dispelled the myth that STAS is an ex vivo artifact. “STAS is morphologically different from tissue floaters and contaminant or extraneous tissues that can lead to diagnostic errors,” they said.
And while the study showed that STAS is an independent predictor of recurrence and cancer-specific death, it was not predictive of overall survival – perhaps because most of the study population was over age 65 and were more likely to die from other causes rather than lung cancer. “We found a strong correlation between STAS and high-grade morphologic patterns such as nuclear size, nuclear atypia, mitotic count and Ki-67 labeling index, suggesting that STAS is associated with tumor proliferation,” Dr. Lu and coauthors said.
“Because we found STAS to show greater prognostic significance than lymphatic vascular, and visceral pleural invasion, all of which are histologic features recommended to be recorded in pathology reports for lung cancer specimens, in the future, STAS may be appropriate to add to this list,” the researchers noted.
Dr. Lu and coauthors had no financial relationships to disclose.
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).
In multivariable models for any recurrence and lung cancer–specific death, the researchers found that STAS was a significant independent predictor for both outcomes (P = .034 and .016, respectively).
“We found that STAS in lung SCC was associated with p-stage, lymphatic and vascular invasion, necrosis, larger nuclear diameter, increased mitoses and high Ki-67 labeling index,” wrote lead author Shaohua Lu, MD, and coauthors (J Thorac Oncol. 2017 Feb;12[2]:223-34). Their findings are based on an analysis of 445 patients who had resection for stage I-III SCC over a 10-year period ending in 2009.
The Sloan-Kettering Group previously reported that STAS was a predictor of recurrence in stage I lung adenocarcinoma patients who had a limited resection (J Thorac Oncol. 2015;10[5]:806-14), and others reported STAS was a clinically significant finding in the disease. In the latest study, Dr. Lu and colleagues set out to determine if STAS is associated with tumor aggressiveness in lung SCC by using a large cohort of patients who had lung SCC resection. The lung resections they studied are from the aforementioned 2015 study that used immunohistochemistry to confirm squamous differentiation in otherwise poorly differentiated tumors.
Two pathologists reviewed tumor slides and used Ki-67 staining to confirm squamous differentiation. The study population comprised 98% former smokers and the median age was 71.3; 76% (336) were older than 65.
Dr. Lu and colleagues noted how STAS in lung SCC differs from its presentation in lung adenocarcinoma. “In contrast to lung adenocarcinoma, in which STAS can manifest as micropapillary clusters, solid nests or single cells, all STAS lesions in lung SCCs consist of solid tumor cell nests,” they wrote.
They found that STAS was associated with a higher risk of recurrence in SCC patients who had lobectomy, but not sublobar resection, whereas in patients with lung adenocarcinoma STAS was associated with a high risk of recurrence if they had sublobar resection.
The study observed STAS in 132 patients (30%). With a median follow-up of 3.4 years, 61% (273) of all patients died in that time. STAS tumors were more aggressive in nature than were non-STAS tumors. Pathologic features strongly associated with STAS were lymphatic invasion (40% for STAS vs. 19% for non-STAS patients); vascular invasion (36% vs. 22%); larger tumor size (median 4 cm vs. 3 cm); higher Ki-67 labeling index (32% vs. 13%); and higher tumor stage (23% with p-stage I, 35% p-stage II, and 43% p-stage III), all significant differences. Patients with STAS also had a higher 5-year cumulative incidence of any recurrence (39% vs. 26%) and lung cancer-specific death (30% vs. 14%), both significant differences.
STAS has an “insidious pattern of tumor invasion” that can be difficult for pathologists to detect and requires the gathering of specimens that include the adjacent lung parenchyma, Dr. Lu and colleagues said. They also dispelled the myth that STAS is an ex vivo artifact. “STAS is morphologically different from tissue floaters and contaminant or extraneous tissues that can lead to diagnostic errors,” they said.
And while the study showed that STAS is an independent predictor of recurrence and cancer-specific death, it was not predictive of overall survival – perhaps because most of the study population was over age 65 and were more likely to die from other causes rather than lung cancer. “We found a strong correlation between STAS and high-grade morphologic patterns such as nuclear size, nuclear atypia, mitotic count and Ki-67 labeling index, suggesting that STAS is associated with tumor proliferation,” Dr. Lu and coauthors said.
“Because we found STAS to show greater prognostic significance than lymphatic vascular, and visceral pleural invasion, all of which are histologic features recommended to be recorded in pathology reports for lung cancer specimens, in the future, STAS may be appropriate to add to this list,” the researchers noted.
Dr. Lu and coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC ONCOLOGY
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
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
HCV testing stagnant among baby boomers
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.
The numbers are particularly troubling because new and improved antiviral drugs offer cures that could forestall liver cancer, cirrhosis, and other potential complications, with shorter regimens and fewer side effects than older regimens.
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.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
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.
The numbers are particularly troubling because new and improved antiviral drugs offer cures that could forestall liver cancer, cirrhosis, and other potential complications, with shorter regimens and fewer side effects than older regimens.
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.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
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.
The numbers are particularly troubling because new and improved antiviral drugs offer cures that could forestall liver cancer, cirrhosis, and other potential complications, with shorter regimens and fewer side effects than older regimens.
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.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
FROM AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Immunotherapy boosts OS from metastatic cervical cancer in early trial
NATIONAL HARBOR, MD – 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.
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.
NATIONAL HARBOR, MD – 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.
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.
NATIONAL HARBOR, MD – 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.
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.
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
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
New Trump travel order could disrupt meetings, trainees
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.
agallegos@frontlinemedcom.com
On Twitter @legal_med
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.
agallegos@frontlinemedcom.com
On Twitter @legal_med
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.
agallegos@frontlinemedcom.com
On Twitter @legal_med
FDA grants Hodgkin lymphoma indication for pembrolizumab
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.
“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.
dbrunk@frontlinemedcom.com
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.
“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.
dbrunk@frontlinemedcom.com
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.
“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.
dbrunk@frontlinemedcom.com
Common gut yeast may exacerbate IBD
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.
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.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point:
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?
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.
“Women had less favorable preoperative characteristics than men but received fewer bilateral-ITA grafts and less all-arterial grafting as part of their revascularization strategy,” Tamer Attia, MD, MSc, and his coauthors said in the study published in the Journal of Thoracic and Cardiovascular Surgery. They also found that women were more likely to die in the hospital after CABG and had lower risk-adjusted long-term survival than men (2017 March;153:571-9).
Survival was lowest in women who were not completely revascularized and had no ITA grafting, while survival was highest in men who were completely revascularized and had bilateral grafting, Dr. Attia and coauthors said.
The researchers’ goal was to use extensive risk adjustment to evaluate how differences in revascularization strategies influenced survival of men and women after CABG. They analyzed 57,943 primary, isolated CABG procedures performed at Cleveland Clinic from 1972 to 2011, including 11,009 procedures in women.
The researchers identified differences between sexes in three key areas: revascularization strategies, in-hospital outcomes, and time-related survival.
With regard to revascularization strategies, while men were significantly more likely to have incomplete revascularization than were women, women received significantly fewer arterial grafts (8.4% vs. 9.3% for men). This included fewer bilateral-ITA grafts and radial artery grafts, less use of total arterial revascularization, and greater use of saphenous vein grafts (SVGs) to the left anterior descending artery. Women were also significantly more likely to receive only SVGs for revascularization (32% vs. 30% for men; P less than .0001). Most operations for both women and men were done with cardiopulmonary bypass, but significantly more women had off-pump procedures (5.4% vs. 2.9%).
In the hospital after operations, women were significantly more prone to postoperative deep sternal–wound infections and septicemias, as well as strokes and renal failure, including dialysis-dependent renal failure. Women also had higher rates of new-onset atrial fibrillation (15% vs. 13% in men), and higher rates of mechanical ventilation for more than 24 hours (13% vs. 9.2%). Women spent more time in the ICU and hospital overall, and their in-hospital death rate was more than double that of men (2.7% vs. 1.1%).
Women also had shorter long-term survival, “and this has persisted since the beginning of CABG at Cleveland Clinic,” Dr. Attia and coauthors said. What’s more, the survival gap between women in the study and women in the general population post CABG was wider than that in men. “After we adjusted for patient and revascularization strategy differences, female sex remained an independent risk factor for death overall and both early and late after CABG.”
Incomplete revascularization had greater consequences for women than for men. At 10 years, 58% of women with incomplete revascularization survived, vs. 70% of men. At 20 years, the rates were 25% for women and 35% for men. “Use of ITA grafts was associated with better survival than use of SVGs alone and was best when bilateral-ITA grafting was performed,” Dr. Attia and coauthors said. However, the study determined that bilateral grafting seems less effective in women long-term. “Hence, a patient’s sex deserves special consideration in operative planning.”
Many questions about CABG in women remain: Identifying which female patients would benefit from more meticulous conduit harvesting, from better coronary artery selection, and from bilateral-ITA grafting and which are less susceptible to sternal would infections could increase appropriate use of bilateral-ITA grafting, the researchers noted. “The difference in effectiveness of bilateral-ITA grafting needs to be considered in women at elevated risk for bilateral-ITA harvesting complications.”
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 relationships to disclose.
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.
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.
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.
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.
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.
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.
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.
“Women had less favorable preoperative characteristics than men but received fewer bilateral-ITA grafts and less all-arterial grafting as part of their revascularization strategy,” Tamer Attia, MD, MSc, and his coauthors said in the study published in the Journal of Thoracic and Cardiovascular Surgery. They also found that women were more likely to die in the hospital after CABG and had lower risk-adjusted long-term survival than men (2017 March;153:571-9).
Survival was lowest in women who were not completely revascularized and had no ITA grafting, while survival was highest in men who were completely revascularized and had bilateral grafting, Dr. Attia and coauthors said.
The researchers’ goal was to use extensive risk adjustment to evaluate how differences in revascularization strategies influenced survival of men and women after CABG. They analyzed 57,943 primary, isolated CABG procedures performed at Cleveland Clinic from 1972 to 2011, including 11,009 procedures in women.
The researchers identified differences between sexes in three key areas: revascularization strategies, in-hospital outcomes, and time-related survival.
With regard to revascularization strategies, while men were significantly more likely to have incomplete revascularization than were women, women received significantly fewer arterial grafts (8.4% vs. 9.3% for men). This included fewer bilateral-ITA grafts and radial artery grafts, less use of total arterial revascularization, and greater use of saphenous vein grafts (SVGs) to the left anterior descending artery. Women were also significantly more likely to receive only SVGs for revascularization (32% vs. 30% for men; P less than .0001). Most operations for both women and men were done with cardiopulmonary bypass, but significantly more women had off-pump procedures (5.4% vs. 2.9%).
In the hospital after operations, women were significantly more prone to postoperative deep sternal–wound infections and septicemias, as well as strokes and renal failure, including dialysis-dependent renal failure. Women also had higher rates of new-onset atrial fibrillation (15% vs. 13% in men), and higher rates of mechanical ventilation for more than 24 hours (13% vs. 9.2%). Women spent more time in the ICU and hospital overall, and their in-hospital death rate was more than double that of men (2.7% vs. 1.1%).
Women also had shorter long-term survival, “and this has persisted since the beginning of CABG at Cleveland Clinic,” Dr. Attia and coauthors said. What’s more, the survival gap between women in the study and women in the general population post CABG was wider than that in men. “After we adjusted for patient and revascularization strategy differences, female sex remained an independent risk factor for death overall and both early and late after CABG.”
Incomplete revascularization had greater consequences for women than for men. At 10 years, 58% of women with incomplete revascularization survived, vs. 70% of men. At 20 years, the rates were 25% for women and 35% for men. “Use of ITA grafts was associated with better survival than use of SVGs alone and was best when bilateral-ITA grafting was performed,” Dr. Attia and coauthors said. However, the study determined that bilateral grafting seems less effective in women long-term. “Hence, a patient’s sex deserves special consideration in operative planning.”
Many questions about CABG in women remain: Identifying which female patients would benefit from more meticulous conduit harvesting, from better coronary artery selection, and from bilateral-ITA grafting and which are less susceptible to sternal would infections could increase appropriate use of bilateral-ITA grafting, the researchers noted. “The difference in effectiveness of bilateral-ITA grafting needs to be considered in women at elevated risk for bilateral-ITA harvesting complications.”
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 relationships to disclose.
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.
“Women had less favorable preoperative characteristics than men but received fewer bilateral-ITA grafts and less all-arterial grafting as part of their revascularization strategy,” Tamer Attia, MD, MSc, and his coauthors said in the study published in the Journal of Thoracic and Cardiovascular Surgery. They also found that women were more likely to die in the hospital after CABG and had lower risk-adjusted long-term survival than men (2017 March;153:571-9).
Survival was lowest in women who were not completely revascularized and had no ITA grafting, while survival was highest in men who were completely revascularized and had bilateral grafting, Dr. Attia and coauthors said.
The researchers’ goal was to use extensive risk adjustment to evaluate how differences in revascularization strategies influenced survival of men and women after CABG. They analyzed 57,943 primary, isolated CABG procedures performed at Cleveland Clinic from 1972 to 2011, including 11,009 procedures in women.
The researchers identified differences between sexes in three key areas: revascularization strategies, in-hospital outcomes, and time-related survival.
With regard to revascularization strategies, while men were significantly more likely to have incomplete revascularization than were women, women received significantly fewer arterial grafts (8.4% vs. 9.3% for men). This included fewer bilateral-ITA grafts and radial artery grafts, less use of total arterial revascularization, and greater use of saphenous vein grafts (SVGs) to the left anterior descending artery. Women were also significantly more likely to receive only SVGs for revascularization (32% vs. 30% for men; P less than .0001). Most operations for both women and men were done with cardiopulmonary bypass, but significantly more women had off-pump procedures (5.4% vs. 2.9%).
In the hospital after operations, women were significantly more prone to postoperative deep sternal–wound infections and septicemias, as well as strokes and renal failure, including dialysis-dependent renal failure. Women also had higher rates of new-onset atrial fibrillation (15% vs. 13% in men), and higher rates of mechanical ventilation for more than 24 hours (13% vs. 9.2%). Women spent more time in the ICU and hospital overall, and their in-hospital death rate was more than double that of men (2.7% vs. 1.1%).
Women also had shorter long-term survival, “and this has persisted since the beginning of CABG at Cleveland Clinic,” Dr. Attia and coauthors said. What’s more, the survival gap between women in the study and women in the general population post CABG was wider than that in men. “After we adjusted for patient and revascularization strategy differences, female sex remained an independent risk factor for death overall and both early and late after CABG.”
Incomplete revascularization had greater consequences for women than for men. At 10 years, 58% of women with incomplete revascularization survived, vs. 70% of men. At 20 years, the rates were 25% for women and 35% for men. “Use of ITA grafts was associated with better survival than use of SVGs alone and was best when bilateral-ITA grafting was performed,” Dr. Attia and coauthors said. However, the study determined that bilateral grafting seems less effective in women long-term. “Hence, a patient’s sex deserves special consideration in operative planning.”
Many questions about CABG in women remain: Identifying which female patients would benefit from more meticulous conduit harvesting, from better coronary artery selection, and from bilateral-ITA grafting and which are less susceptible to sternal would infections could increase appropriate use of bilateral-ITA grafting, the researchers noted. “The difference in effectiveness of bilateral-ITA grafting needs to be considered in women at elevated risk for bilateral-ITA harvesting complications.”
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 relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
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.
By The Numbers: Trump’s choice for FDA chief is versatile, entrenched in Pharma
President Donald Trump’s pick to lead the Food and Drug Administration has deep ties to the pharmaceutical industry as a consultant, investor, and board member. Scott Gottlieb, MD, 44, also has worn many hats in a career that included two previous stints at the FDA, practicing as a physician, and writer/editor roles at prestigious medical journals.
“It seems like the main question is, ‘Which Gottlieb are we going to get?’” said Dr. Robert Califf, who stepped down from his position as the commissioner of the Food and Drug Administration in January.
Here’s a look at Dr. Gottlieb’s career, by the numbers:
188 companies
New Enterprise Associates, the venture capital firm in which Dr. Gottlieb is a partner, is currently or has been invested in 188 health care companies.
8 boards of directors
Dr. Gottlieb serves or has served on eight boards of directors, according to his LinkedIn profile. The firms include pharmaceutical companies Gradalis and Tolero Pharmaceuticals, which are developing cancer treatments, among other things; and Glytec, which offers glycemic management tools for patients with diabetes.
8 drug and device companies
Eight pharmaceutical companies disclosed payments to Dr. Gottlieb in 2015, according to the open payments database: Vertex Pharmaceuticals, GlaxoSmithKline, Daiichi, Valeant, Pfizer, Millennium, SI-BONE, and E.R. Squibb & Sons. Payments included travel to Philadelphia, San Francisco, and London.
9 recusals
In a memo, Dr. Gottlieb wrote that he had a consulting relationship with nine health care companies before his stint as the FDA’s deputy commissioner for medical and scientific affairs during the George W. Bush administration. Those ties disqualified him from dealing with matters concerning those companies for at least a year. The firms included Eli Lilly, Roche, and Sanofi-Aventis.
The recusals generated some headlines during the avian flu scare because Dr. Gottlieb had to recuse himself from some of the planning efforts around vaccines.
7 years
Starting in 1997, Dr. Gottlieb spent 7 years as a staff writer for BMJ, one of the top medical journals in the world. And he was an editor at the Pulse section of JAMA, the Journal of the American Medical Association, from 1996 to 2001.
Dr. Gottlieb also spent the past 7 years as an adviser to drug maker GlaxoSmithKline’s product investment board, according to his LinkedIn page.
33 years old
Dr. Gottlieb was 33 when he got the No. 2 job at the FDA in 2005. He had done a short stint at the agency a few years earlier but was considered a controversial pick because of his ties to Wall Street. He stayed until 2007.
“He has done a lot of thinking about how FDA should be managed – his operational sophistication is going to be a great asset,” said former FDA attorney Coleen Klasmeier, who worked with Dr. Gottlieb and coauthored articles with him. “He also has very strong relationships among career FDA personnel and will be able to hit the ground running on a range of important initiatives.”
18 times before Congress
Dr. Gottlieb testified before Congress as an expert witness 18 times. He has spoken about drug prices, revamping the FDA approval process and the vaccine supply.
“Most people watching at the FDA would breathe a sigh of relief,” Joshua Sharfstein, MD, who served as the FDA’s principal deputy commissioner until 2011, said of Dr. Gottlieb’s impending nomination. He added that Dr. Gottlieb is “not someone who has expressed antagonism to the core principles of the agency.”
36,000 Twitter followers
More than 36,000 people follow Dr. Gottlieb on Twitter, although he follows only 845 people, as of Tuesday. He has tweeted at least 10,400 times, lately about different strains of the flu.
72 percent
Almost three-fourths of the 53 drug companies surveyed by Mizuho said they’d prefer Dr. Gottlieb to head the FDA.
$414,000
Pharmaceutical companies paid Dr. Gottlieb nearly $414,000 from 2013 through 2015, according to federal open payments data, for speeches, consulting, travel, and meals.
That included $65,780 from a pharmaceutical company to promote a controversial cystic fibrosis drug called Kalydeco (ivacaftor). Only one other doctor received more money toward promoting the drug.
The drug’s price tag was controversial because the nonprofit Cystic Fibrosis Foundation kicked in $150 million toward finding a cure for the fatal disease and got a rich $3.3 billion payday for selling its rights to royalties for the drug. Vertex Pharmaceuticals priced Kalydeco at more than $300,000 a year.
Nearly $30,000
Dr. Gottlieb has contributed nearly $30,000 toward Republican political campaigns and joint fundraising committees from 2005 to 2014. He has donated toward the presidential runs of Mitt Romney and Sen. John McCain. He also donated more than once to Speaker Paul Ryan.
Dr. Gottlieb contributed the most money toward Sen. Ben Sasse (R-Neb.), spending $2,600 in the primary and $2,600 again in the general election in 2013. Sen. Sasse was a vocal anti-Trump supporter, penning an open letter in February 2016 about how he could not support Trump, who was “dividing” the nation, in his view.
“But have you noticed how Mr. Trump uses the word ‘Reign’ – like he thinks he’s running for King?” Sen. Sasse asked in the post.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
President Donald Trump’s pick to lead the Food and Drug Administration has deep ties to the pharmaceutical industry as a consultant, investor, and board member. Scott Gottlieb, MD, 44, also has worn many hats in a career that included two previous stints at the FDA, practicing as a physician, and writer/editor roles at prestigious medical journals.
“It seems like the main question is, ‘Which Gottlieb are we going to get?’” said Dr. Robert Califf, who stepped down from his position as the commissioner of the Food and Drug Administration in January.
Here’s a look at Dr. Gottlieb’s career, by the numbers:
188 companies
New Enterprise Associates, the venture capital firm in which Dr. Gottlieb is a partner, is currently or has been invested in 188 health care companies.
8 boards of directors
Dr. Gottlieb serves or has served on eight boards of directors, according to his LinkedIn profile. The firms include pharmaceutical companies Gradalis and Tolero Pharmaceuticals, which are developing cancer treatments, among other things; and Glytec, which offers glycemic management tools for patients with diabetes.
8 drug and device companies
Eight pharmaceutical companies disclosed payments to Dr. Gottlieb in 2015, according to the open payments database: Vertex Pharmaceuticals, GlaxoSmithKline, Daiichi, Valeant, Pfizer, Millennium, SI-BONE, and E.R. Squibb & Sons. Payments included travel to Philadelphia, San Francisco, and London.
9 recusals
In a memo, Dr. Gottlieb wrote that he had a consulting relationship with nine health care companies before his stint as the FDA’s deputy commissioner for medical and scientific affairs during the George W. Bush administration. Those ties disqualified him from dealing with matters concerning those companies for at least a year. The firms included Eli Lilly, Roche, and Sanofi-Aventis.
The recusals generated some headlines during the avian flu scare because Dr. Gottlieb had to recuse himself from some of the planning efforts around vaccines.
7 years
Starting in 1997, Dr. Gottlieb spent 7 years as a staff writer for BMJ, one of the top medical journals in the world. And he was an editor at the Pulse section of JAMA, the Journal of the American Medical Association, from 1996 to 2001.
Dr. Gottlieb also spent the past 7 years as an adviser to drug maker GlaxoSmithKline’s product investment board, according to his LinkedIn page.
33 years old
Dr. Gottlieb was 33 when he got the No. 2 job at the FDA in 2005. He had done a short stint at the agency a few years earlier but was considered a controversial pick because of his ties to Wall Street. He stayed until 2007.
“He has done a lot of thinking about how FDA should be managed – his operational sophistication is going to be a great asset,” said former FDA attorney Coleen Klasmeier, who worked with Dr. Gottlieb and coauthored articles with him. “He also has very strong relationships among career FDA personnel and will be able to hit the ground running on a range of important initiatives.”
18 times before Congress
Dr. Gottlieb testified before Congress as an expert witness 18 times. He has spoken about drug prices, revamping the FDA approval process and the vaccine supply.
“Most people watching at the FDA would breathe a sigh of relief,” Joshua Sharfstein, MD, who served as the FDA’s principal deputy commissioner until 2011, said of Dr. Gottlieb’s impending nomination. He added that Dr. Gottlieb is “not someone who has expressed antagonism to the core principles of the agency.”
36,000 Twitter followers
More than 36,000 people follow Dr. Gottlieb on Twitter, although he follows only 845 people, as of Tuesday. He has tweeted at least 10,400 times, lately about different strains of the flu.
72 percent
Almost three-fourths of the 53 drug companies surveyed by Mizuho said they’d prefer Dr. Gottlieb to head the FDA.
$414,000
Pharmaceutical companies paid Dr. Gottlieb nearly $414,000 from 2013 through 2015, according to federal open payments data, for speeches, consulting, travel, and meals.
That included $65,780 from a pharmaceutical company to promote a controversial cystic fibrosis drug called Kalydeco (ivacaftor). Only one other doctor received more money toward promoting the drug.
The drug’s price tag was controversial because the nonprofit Cystic Fibrosis Foundation kicked in $150 million toward finding a cure for the fatal disease and got a rich $3.3 billion payday for selling its rights to royalties for the drug. Vertex Pharmaceuticals priced Kalydeco at more than $300,000 a year.
Nearly $30,000
Dr. Gottlieb has contributed nearly $30,000 toward Republican political campaigns and joint fundraising committees from 2005 to 2014. He has donated toward the presidential runs of Mitt Romney and Sen. John McCain. He also donated more than once to Speaker Paul Ryan.
Dr. Gottlieb contributed the most money toward Sen. Ben Sasse (R-Neb.), spending $2,600 in the primary and $2,600 again in the general election in 2013. Sen. Sasse was a vocal anti-Trump supporter, penning an open letter in February 2016 about how he could not support Trump, who was “dividing” the nation, in his view.
“But have you noticed how Mr. Trump uses the word ‘Reign’ – like he thinks he’s running for King?” Sen. Sasse asked in the post.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
President Donald Trump’s pick to lead the Food and Drug Administration has deep ties to the pharmaceutical industry as a consultant, investor, and board member. Scott Gottlieb, MD, 44, also has worn many hats in a career that included two previous stints at the FDA, practicing as a physician, and writer/editor roles at prestigious medical journals.
“It seems like the main question is, ‘Which Gottlieb are we going to get?’” said Dr. Robert Califf, who stepped down from his position as the commissioner of the Food and Drug Administration in January.
Here’s a look at Dr. Gottlieb’s career, by the numbers:
188 companies
New Enterprise Associates, the venture capital firm in which Dr. Gottlieb is a partner, is currently or has been invested in 188 health care companies.
8 boards of directors
Dr. Gottlieb serves or has served on eight boards of directors, according to his LinkedIn profile. The firms include pharmaceutical companies Gradalis and Tolero Pharmaceuticals, which are developing cancer treatments, among other things; and Glytec, which offers glycemic management tools for patients with diabetes.
8 drug and device companies
Eight pharmaceutical companies disclosed payments to Dr. Gottlieb in 2015, according to the open payments database: Vertex Pharmaceuticals, GlaxoSmithKline, Daiichi, Valeant, Pfizer, Millennium, SI-BONE, and E.R. Squibb & Sons. Payments included travel to Philadelphia, San Francisco, and London.
9 recusals
In a memo, Dr. Gottlieb wrote that he had a consulting relationship with nine health care companies before his stint as the FDA’s deputy commissioner for medical and scientific affairs during the George W. Bush administration. Those ties disqualified him from dealing with matters concerning those companies for at least a year. The firms included Eli Lilly, Roche, and Sanofi-Aventis.
The recusals generated some headlines during the avian flu scare because Dr. Gottlieb had to recuse himself from some of the planning efforts around vaccines.
7 years
Starting in 1997, Dr. Gottlieb spent 7 years as a staff writer for BMJ, one of the top medical journals in the world. And he was an editor at the Pulse section of JAMA, the Journal of the American Medical Association, from 1996 to 2001.
Dr. Gottlieb also spent the past 7 years as an adviser to drug maker GlaxoSmithKline’s product investment board, according to his LinkedIn page.
33 years old
Dr. Gottlieb was 33 when he got the No. 2 job at the FDA in 2005. He had done a short stint at the agency a few years earlier but was considered a controversial pick because of his ties to Wall Street. He stayed until 2007.
“He has done a lot of thinking about how FDA should be managed – his operational sophistication is going to be a great asset,” said former FDA attorney Coleen Klasmeier, who worked with Dr. Gottlieb and coauthored articles with him. “He also has very strong relationships among career FDA personnel and will be able to hit the ground running on a range of important initiatives.”
18 times before Congress
Dr. Gottlieb testified before Congress as an expert witness 18 times. He has spoken about drug prices, revamping the FDA approval process and the vaccine supply.
“Most people watching at the FDA would breathe a sigh of relief,” Joshua Sharfstein, MD, who served as the FDA’s principal deputy commissioner until 2011, said of Dr. Gottlieb’s impending nomination. He added that Dr. Gottlieb is “not someone who has expressed antagonism to the core principles of the agency.”
36,000 Twitter followers
More than 36,000 people follow Dr. Gottlieb on Twitter, although he follows only 845 people, as of Tuesday. He has tweeted at least 10,400 times, lately about different strains of the flu.
72 percent
Almost three-fourths of the 53 drug companies surveyed by Mizuho said they’d prefer Dr. Gottlieb to head the FDA.
$414,000
Pharmaceutical companies paid Dr. Gottlieb nearly $414,000 from 2013 through 2015, according to federal open payments data, for speeches, consulting, travel, and meals.
That included $65,780 from a pharmaceutical company to promote a controversial cystic fibrosis drug called Kalydeco (ivacaftor). Only one other doctor received more money toward promoting the drug.
The drug’s price tag was controversial because the nonprofit Cystic Fibrosis Foundation kicked in $150 million toward finding a cure for the fatal disease and got a rich $3.3 billion payday for selling its rights to royalties for the drug. Vertex Pharmaceuticals priced Kalydeco at more than $300,000 a year.
Nearly $30,000
Dr. Gottlieb has contributed nearly $30,000 toward Republican political campaigns and joint fundraising committees from 2005 to 2014. He has donated toward the presidential runs of Mitt Romney and Sen. John McCain. He also donated more than once to Speaker Paul Ryan.
Dr. Gottlieb contributed the most money toward Sen. Ben Sasse (R-Neb.), spending $2,600 in the primary and $2,600 again in the general election in 2013. Sen. Sasse was a vocal anti-Trump supporter, penning an open letter in February 2016 about how he could not support Trump, who was “dividing” the nation, in his view.
“But have you noticed how Mr. Trump uses the word ‘Reign’ – like he thinks he’s running for King?” Sen. Sasse asked in the post.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.