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T receptor diversity may predict BCP-ALL response to blinatumomab
MADRID – For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.
Patients with responses to blinatumomab had a significantly more diverse T-cell receptor–beta (TRB) gene repertoire at the time of screening, compared with patients who would go on to have minimal residual disease after starting on blinatumomab therapy, reported Michaela Kotrova, MD, from the 2nd Faculty of Medicine Charles University and University Hospital Motol in Prague, Czech Republic.
Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.
They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.
Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.
They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).
They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.
On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.
Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.
The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.
MADRID – For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.
Patients with responses to blinatumomab had a significantly more diverse T-cell receptor–beta (TRB) gene repertoire at the time of screening, compared with patients who would go on to have minimal residual disease after starting on blinatumomab therapy, reported Michaela Kotrova, MD, from the 2nd Faculty of Medicine Charles University and University Hospital Motol in Prague, Czech Republic.
Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.
They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.
Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.
They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).
They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.
On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.
Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.
The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.
MADRID – For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.
Patients with responses to blinatumomab had a significantly more diverse T-cell receptor–beta (TRB) gene repertoire at the time of screening, compared with patients who would go on to have minimal residual disease after starting on blinatumomab therapy, reported Michaela Kotrova, MD, from the 2nd Faculty of Medicine Charles University and University Hospital Motol in Prague, Czech Republic.
Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.
They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.
Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.
They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).
They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.
On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.
Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.
The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.
AT EHA 2017
Key clinical point: T-cell receptor–beta diversity is important for protection against a wide variety of pathogens.
Major finding: Patients with responses to blinatumomab had a significantly more diverse TRB gene repertoire at the time of screening, compared with patients who would go on to have minimal residual disease after starting on blinatumomab therapy.
Data source: A next-generation sequencing study of samples from 114 patients with relapsed/refractory B-cell precursor acute lymphocytic leukemia.
Disclosures: The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.
Dermatologist calls for paradigm shift on treating ocular rosacea
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
Childhood asthma linked to high LV mass later
A history of childhood asthma correlates with high left ventricular mass, a prominent indicator of cardiac damage, in asymptomatic healthy young adults, according to a report published online June 26 in JACC: Heart Failure.
“Our data suggest that aggressive lifestyle modifications or even pharmacologic treatment may be applied to people with a [childhood] history of asthma. … to lower cardiovascular risk,” said Dianjianyi Sun, MD, PhD, of the department of epidemiology, Tulane University, New Orleans, and his associates.
Both mean left ventricular mass (169 g) and mean left ventricular mass index (41 g/m2) were significantly higher in participants who’d had childhood asthma than in those who had not (158 g and 38 g/m2, respectively). This correlation was independent of major cardiovascular risk factors such as race, smoking status, hypertension status, use of antihypertensive medications, C-reactive protein levels, heart rate, and body mass index, the investigators said (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.03.009).
The association was strongest among young adults who had higher systolic blood pressure (prehypertension or hypertension).
This study was supported by the National Institutes of Health, the Boston Obesity Nutrition Research Center, the United States-Israel Binational Science Foundation, and the American Heart Association. Dr. Sun and his associates reported having no relevant financial disclosures.
Sun et al. report that healthy young adults who had asthma during childhood have a significantly greater left ventricular mass index, by about 8%, than do those who didn’t have the condition.
On an individual patient level, such a difference confers a relatively small incremental risk of incident cardiovascular disease: a roughly 1.08-fold increase. However, at the population level, where there are many major comorbidities, the public health implications could be substantial. Targeting these patients for intensified cardiovascular risk reduction could have important benefits.
John S. Gottdiener, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Gottdiener made these remarks in an editorial comment accompanying Dr. Sun’s report (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.05.003).
Sun et al. report that healthy young adults who had asthma during childhood have a significantly greater left ventricular mass index, by about 8%, than do those who didn’t have the condition.
On an individual patient level, such a difference confers a relatively small incremental risk of incident cardiovascular disease: a roughly 1.08-fold increase. However, at the population level, where there are many major comorbidities, the public health implications could be substantial. Targeting these patients for intensified cardiovascular risk reduction could have important benefits.
John S. Gottdiener, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Gottdiener made these remarks in an editorial comment accompanying Dr. Sun’s report (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.05.003).
Sun et al. report that healthy young adults who had asthma during childhood have a significantly greater left ventricular mass index, by about 8%, than do those who didn’t have the condition.
On an individual patient level, such a difference confers a relatively small incremental risk of incident cardiovascular disease: a roughly 1.08-fold increase. However, at the population level, where there are many major comorbidities, the public health implications could be substantial. Targeting these patients for intensified cardiovascular risk reduction could have important benefits.
John S. Gottdiener, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Gottdiener made these remarks in an editorial comment accompanying Dr. Sun’s report (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.05.003).
A history of childhood asthma correlates with high left ventricular mass, a prominent indicator of cardiac damage, in asymptomatic healthy young adults, according to a report published online June 26 in JACC: Heart Failure.
“Our data suggest that aggressive lifestyle modifications or even pharmacologic treatment may be applied to people with a [childhood] history of asthma. … to lower cardiovascular risk,” said Dianjianyi Sun, MD, PhD, of the department of epidemiology, Tulane University, New Orleans, and his associates.
Both mean left ventricular mass (169 g) and mean left ventricular mass index (41 g/m2) were significantly higher in participants who’d had childhood asthma than in those who had not (158 g and 38 g/m2, respectively). This correlation was independent of major cardiovascular risk factors such as race, smoking status, hypertension status, use of antihypertensive medications, C-reactive protein levels, heart rate, and body mass index, the investigators said (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.03.009).
The association was strongest among young adults who had higher systolic blood pressure (prehypertension or hypertension).
This study was supported by the National Institutes of Health, the Boston Obesity Nutrition Research Center, the United States-Israel Binational Science Foundation, and the American Heart Association. Dr. Sun and his associates reported having no relevant financial disclosures.
A history of childhood asthma correlates with high left ventricular mass, a prominent indicator of cardiac damage, in asymptomatic healthy young adults, according to a report published online June 26 in JACC: Heart Failure.
“Our data suggest that aggressive lifestyle modifications or even pharmacologic treatment may be applied to people with a [childhood] history of asthma. … to lower cardiovascular risk,” said Dianjianyi Sun, MD, PhD, of the department of epidemiology, Tulane University, New Orleans, and his associates.
Both mean left ventricular mass (169 g) and mean left ventricular mass index (41 g/m2) were significantly higher in participants who’d had childhood asthma than in those who had not (158 g and 38 g/m2, respectively). This correlation was independent of major cardiovascular risk factors such as race, smoking status, hypertension status, use of antihypertensive medications, C-reactive protein levels, heart rate, and body mass index, the investigators said (JACC: Heart Failure. 2017 Jun 26. doi: 10.1016/j.jchf.2017.03.009).
The association was strongest among young adults who had higher systolic blood pressure (prehypertension or hypertension).
This study was supported by the National Institutes of Health, the Boston Obesity Nutrition Research Center, the United States-Israel Binational Science Foundation, and the American Heart Association. Dr. Sun and his associates reported having no relevant financial disclosures.
FROM JACC: HEART FAILURE
Key clinical point: Childhood asthma is associated with high left ventricular mass in asymptomatic young adults.
Major finding: Both mean left ventricular mass (169 g) and mean left ventricular mass index (41 g/m2) were significantly higher in participants who’d had childhood asthma than in those who had not (158 g and 38 g/m2, respectively).
Data source: A secondary analysis of data from the Bogalusa Heart Study, involving 1,118 participants followed for an average of 10 years.
Disclosures: This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Boston Obesity Nutrition Research Center, the United States-Israel Binational Science Foundation, and the American Heart Association. Dr. Sun and his associates reported having no relevant financial disclosures.
Hospital antibiograms may not apply to emergency department patients
NEW ORLEANS – Patients seen in the emergency department present with a wider range of risk for resistant infections than do hospitalized patients overall, and as a result, hospital-wide antibiograms that dictate empiric therapy may not translate well to the ED setting, a study showed.
Instead, investigators suggested that clinicians choose empiric antimicrobial therapy in the emergency department based on factors associated with differences in susceptibility.
The study researchers compared common antibiotics to treat Escherichia coli between adults treated at their institution overall versus the emergency department, and by sex, patient age, and whether people came to the ED from home versus a long-term care setting. They found some significant differences that could guide empiric treatment in the ED setting.
“Our ED pharmacist observed a lot of broad-spectrum antibiotic prescribing for UTIs,” lead investigator Sarah Jorgensen, PharmD, said at the annual meeting of the American Society for Microbiology. “Also, we’ve had a culture follow-up program in place for the last 5 years, and they had to intervene on a lot of postdischarge antibiotic mismatches.”
E. coli was the most common urinary pathogen detected in this study of 500 randomly selected ED patients with ICD-9/ICD-10 diagnostic codes for urinary tract infection. Investigators found E. coli in 64% of the 226 culture-positive patients presenting to the ED at Huntington Hospital in Pasadena, Calif., between July 2015 and June 2016.
“What was surprising for us, because our enrollment was based on ICD codes for a UTI, is that only about 50% had a positive urine culture,” said Dr. Jorgensen, a pharmacy resident at the University of Southern California in Los Angeles. “Urinalysis was positive in about 99% of the population.”
Dr. Jorgensen and her colleagues found overall low susceptibilities of 71% for ciprofloxacin, 66% for trimethoprim/sulfamethoxazole, and 67% for cefazolin susceptibilities in the ED. They also found that 8% of isolates were positive for extended-spectrum beta-lactamase isolates, as were 1% of E. coli isolates.
The 67% cefazolin susceptibility was significantly lower in the ED, compared with the 86% susceptibility in the institutional antibiogram (P less than .001).
The investigators found E. coli susceptibility to ciprofloxacin was lower in men, at 55%, compared with 74% among women, but the difference was not statistically significant (P = .14). A similar pattern emerged with cefazolin – 55% susceptibility among men and 69% among women (P = .26). In contrast, trimethoprim/sulfamethoxazole susceptibility trended higher in men, at 73%, vs. 64% among women in the ED (P = .63).
When they divided patients by age 50 years and younger versus those older than 50, the investigators found ampicillin susceptibilities were lower in the younger group, at 30%, compared with 51% among those in the older cohort (P = .03). Similarly, gentamicin susceptibilities were 80% in the younger group, compared with 92% in the older group (P = .04).
Ciprofloxacin susceptibility was significantly lower among people coming to the ED from a long-term care facility than among those coming from home – 35% vs. 77% (P less than .001). Differences in ciprofloxacin susceptibility between admitted and discharged patients was less striking – 63% vs. 78% (P = .04).
Nitrofurantoin was the only oral agent with susceptibility greater than 80% in all patient groups, with susceptibility ranging from 88% to 100%.
Because it typically takes 2-3 days to get the susceptibility results back at Huntington Hospital, many patients are discharged on empiric therapy, noted Mira Zurayk, PharmD, a resident at Huntington Hospital. That can present multiple challenges, particularly with homeless patients who are difficult to find and provide follow-up for, Dr. Jorgensen added.
Based partly on the study findings, the investigators developed a clinical algorithm specifically to address UTI antimicrobial prescriptions in the ED. The algorithm incorporates different recommendations for different groups of patients because of their different resistance trends.
“I think that is a good way to tailor empiric therapy when you don’t have culture results up front,” Dr. Jorgensen said. “We just implemented the algorithm, and I’m now analyzing the outcomes.”
Having more data on outcomes will help the clinicians target lowering the rate of “drug-bug mismatches,” as well as UTI-related revisits to the ED. In addition, the work could help expand the antibiotic stewardship program in the hospital to the ED for the first time, Dr. Jorgensen said.
Dr. Jorgensen and Dr. Zurayk had no relevant financial disclosures. One of the study coauthors, Annie Wong-Beringer, PharmD, receives grant funding from Merck.
NEW ORLEANS – Patients seen in the emergency department present with a wider range of risk for resistant infections than do hospitalized patients overall, and as a result, hospital-wide antibiograms that dictate empiric therapy may not translate well to the ED setting, a study showed.
Instead, investigators suggested that clinicians choose empiric antimicrobial therapy in the emergency department based on factors associated with differences in susceptibility.
The study researchers compared common antibiotics to treat Escherichia coli between adults treated at their institution overall versus the emergency department, and by sex, patient age, and whether people came to the ED from home versus a long-term care setting. They found some significant differences that could guide empiric treatment in the ED setting.
“Our ED pharmacist observed a lot of broad-spectrum antibiotic prescribing for UTIs,” lead investigator Sarah Jorgensen, PharmD, said at the annual meeting of the American Society for Microbiology. “Also, we’ve had a culture follow-up program in place for the last 5 years, and they had to intervene on a lot of postdischarge antibiotic mismatches.”
E. coli was the most common urinary pathogen detected in this study of 500 randomly selected ED patients with ICD-9/ICD-10 diagnostic codes for urinary tract infection. Investigators found E. coli in 64% of the 226 culture-positive patients presenting to the ED at Huntington Hospital in Pasadena, Calif., between July 2015 and June 2016.
“What was surprising for us, because our enrollment was based on ICD codes for a UTI, is that only about 50% had a positive urine culture,” said Dr. Jorgensen, a pharmacy resident at the University of Southern California in Los Angeles. “Urinalysis was positive in about 99% of the population.”
Dr. Jorgensen and her colleagues found overall low susceptibilities of 71% for ciprofloxacin, 66% for trimethoprim/sulfamethoxazole, and 67% for cefazolin susceptibilities in the ED. They also found that 8% of isolates were positive for extended-spectrum beta-lactamase isolates, as were 1% of E. coli isolates.
The 67% cefazolin susceptibility was significantly lower in the ED, compared with the 86% susceptibility in the institutional antibiogram (P less than .001).
The investigators found E. coli susceptibility to ciprofloxacin was lower in men, at 55%, compared with 74% among women, but the difference was not statistically significant (P = .14). A similar pattern emerged with cefazolin – 55% susceptibility among men and 69% among women (P = .26). In contrast, trimethoprim/sulfamethoxazole susceptibility trended higher in men, at 73%, vs. 64% among women in the ED (P = .63).
When they divided patients by age 50 years and younger versus those older than 50, the investigators found ampicillin susceptibilities were lower in the younger group, at 30%, compared with 51% among those in the older cohort (P = .03). Similarly, gentamicin susceptibilities were 80% in the younger group, compared with 92% in the older group (P = .04).
Ciprofloxacin susceptibility was significantly lower among people coming to the ED from a long-term care facility than among those coming from home – 35% vs. 77% (P less than .001). Differences in ciprofloxacin susceptibility between admitted and discharged patients was less striking – 63% vs. 78% (P = .04).
Nitrofurantoin was the only oral agent with susceptibility greater than 80% in all patient groups, with susceptibility ranging from 88% to 100%.
Because it typically takes 2-3 days to get the susceptibility results back at Huntington Hospital, many patients are discharged on empiric therapy, noted Mira Zurayk, PharmD, a resident at Huntington Hospital. That can present multiple challenges, particularly with homeless patients who are difficult to find and provide follow-up for, Dr. Jorgensen added.
Based partly on the study findings, the investigators developed a clinical algorithm specifically to address UTI antimicrobial prescriptions in the ED. The algorithm incorporates different recommendations for different groups of patients because of their different resistance trends.
“I think that is a good way to tailor empiric therapy when you don’t have culture results up front,” Dr. Jorgensen said. “We just implemented the algorithm, and I’m now analyzing the outcomes.”
Having more data on outcomes will help the clinicians target lowering the rate of “drug-bug mismatches,” as well as UTI-related revisits to the ED. In addition, the work could help expand the antibiotic stewardship program in the hospital to the ED for the first time, Dr. Jorgensen said.
Dr. Jorgensen and Dr. Zurayk had no relevant financial disclosures. One of the study coauthors, Annie Wong-Beringer, PharmD, receives grant funding from Merck.
NEW ORLEANS – Patients seen in the emergency department present with a wider range of risk for resistant infections than do hospitalized patients overall, and as a result, hospital-wide antibiograms that dictate empiric therapy may not translate well to the ED setting, a study showed.
Instead, investigators suggested that clinicians choose empiric antimicrobial therapy in the emergency department based on factors associated with differences in susceptibility.
The study researchers compared common antibiotics to treat Escherichia coli between adults treated at their institution overall versus the emergency department, and by sex, patient age, and whether people came to the ED from home versus a long-term care setting. They found some significant differences that could guide empiric treatment in the ED setting.
“Our ED pharmacist observed a lot of broad-spectrum antibiotic prescribing for UTIs,” lead investigator Sarah Jorgensen, PharmD, said at the annual meeting of the American Society for Microbiology. “Also, we’ve had a culture follow-up program in place for the last 5 years, and they had to intervene on a lot of postdischarge antibiotic mismatches.”
E. coli was the most common urinary pathogen detected in this study of 500 randomly selected ED patients with ICD-9/ICD-10 diagnostic codes for urinary tract infection. Investigators found E. coli in 64% of the 226 culture-positive patients presenting to the ED at Huntington Hospital in Pasadena, Calif., between July 2015 and June 2016.
“What was surprising for us, because our enrollment was based on ICD codes for a UTI, is that only about 50% had a positive urine culture,” said Dr. Jorgensen, a pharmacy resident at the University of Southern California in Los Angeles. “Urinalysis was positive in about 99% of the population.”
Dr. Jorgensen and her colleagues found overall low susceptibilities of 71% for ciprofloxacin, 66% for trimethoprim/sulfamethoxazole, and 67% for cefazolin susceptibilities in the ED. They also found that 8% of isolates were positive for extended-spectrum beta-lactamase isolates, as were 1% of E. coli isolates.
The 67% cefazolin susceptibility was significantly lower in the ED, compared with the 86% susceptibility in the institutional antibiogram (P less than .001).
The investigators found E. coli susceptibility to ciprofloxacin was lower in men, at 55%, compared with 74% among women, but the difference was not statistically significant (P = .14). A similar pattern emerged with cefazolin – 55% susceptibility among men and 69% among women (P = .26). In contrast, trimethoprim/sulfamethoxazole susceptibility trended higher in men, at 73%, vs. 64% among women in the ED (P = .63).
When they divided patients by age 50 years and younger versus those older than 50, the investigators found ampicillin susceptibilities were lower in the younger group, at 30%, compared with 51% among those in the older cohort (P = .03). Similarly, gentamicin susceptibilities were 80% in the younger group, compared with 92% in the older group (P = .04).
Ciprofloxacin susceptibility was significantly lower among people coming to the ED from a long-term care facility than among those coming from home – 35% vs. 77% (P less than .001). Differences in ciprofloxacin susceptibility between admitted and discharged patients was less striking – 63% vs. 78% (P = .04).
Nitrofurantoin was the only oral agent with susceptibility greater than 80% in all patient groups, with susceptibility ranging from 88% to 100%.
Because it typically takes 2-3 days to get the susceptibility results back at Huntington Hospital, many patients are discharged on empiric therapy, noted Mira Zurayk, PharmD, a resident at Huntington Hospital. That can present multiple challenges, particularly with homeless patients who are difficult to find and provide follow-up for, Dr. Jorgensen added.
Based partly on the study findings, the investigators developed a clinical algorithm specifically to address UTI antimicrobial prescriptions in the ED. The algorithm incorporates different recommendations for different groups of patients because of their different resistance trends.
“I think that is a good way to tailor empiric therapy when you don’t have culture results up front,” Dr. Jorgensen said. “We just implemented the algorithm, and I’m now analyzing the outcomes.”
Having more data on outcomes will help the clinicians target lowering the rate of “drug-bug mismatches,” as well as UTI-related revisits to the ED. In addition, the work could help expand the antibiotic stewardship program in the hospital to the ED for the first time, Dr. Jorgensen said.
Dr. Jorgensen and Dr. Zurayk had no relevant financial disclosures. One of the study coauthors, Annie Wong-Beringer, PharmD, receives grant funding from Merck.
AT ASM MICROBE 2017
Key clinical point: Escherichia coli susceptibility to common antibiotics in the emergency department varies by age, sex, and admitted versus discharge status.
Major finding: The only oral antimicrobial with greater than 80% susceptibility across all groups was nitrofurantoin.
Data source: A study of 500 randomly selected adults who presented to the ED with a urinary tract infection, based on ICD-9 or ICD-10 codes.
Disclosures: Dr. Jorgensen and Dr. Zurayk had no relevant financial disclosures. One study coauthor, Annie Wong-Beringer, PharmD, receives grant funding from Merck.
Supreme Court allows partial travel ban to proceed
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised 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 executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified 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. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised 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 executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified 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. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised 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 executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified 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. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
Pembrolizumab + rituximab boost response rates in relapsed follicular lymphoma
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
AT 14-ICML
Key clinical point: The combination of pembrolizumab and rituximab increased responses compared with repeat rituximab in patients with relapsed follicular lymphoma.
Major finding: The overall response rate with the combination was 65%, including 50% complete responses.
Data source: Open-label, phase II, single-arm study in 32 patients with relapsed follicular lymphoma (20 for efficacy, 30 for safety analysis).
Disclosures: The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
Updated Analysis of Ocrelizumab’s Safety
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.” 
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
New Tool Can Distinguish Between Tremor Syndromes
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease. 
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease.
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease.
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
Bilateral cellulitis on legs? Think venous stasis dermatitis
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
AT THE ANNUAL ADVANCES IN INTERNAL MEDICINE
Endo hubris
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
