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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
Sharpest spikes in pediatric diabetes seen in Asian, Pacific Islander youth
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
FROM THE MORBIDITY AND MORTALITY WEEKLY REPORT
Exercise PH poised for comeback as new definition takes hold
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Shorter time to metastases associated with worse RCC outcomes
in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.
“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.
In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.
They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).
Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).
On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.
“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.
The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.
Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).
The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.
in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.
“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.
In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.
They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).
Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).
On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.
“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.
The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.
Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).
The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.
in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.
“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.
In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.
They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).
Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).
On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.
“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.
The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.
Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).
The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.
FROM EUROPEAN UROLOGY ONCOLOGY
Lorcaserin withdrawn from U.S. market due to cancer risk
The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.
In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”
Eisai is complying with the withdrawal request.
The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.
“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.
In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.
The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.
Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.
They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.
The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.
In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”
Eisai is complying with the withdrawal request.
The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.
“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.
In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.
The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.
Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.
They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.
The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.
In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”
Eisai is complying with the withdrawal request.
The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.
“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.
In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.
The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.
Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.
They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.
Nonspecific musculoskeletal symptoms might indicate early PsA
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
People with psoriatic arthritis can be symptomatic for years before the condition is diagnosed, according to two recent reports.
There are no reliable diagnostic biomarkers, and sometimes patients have vague symptoms with only minimal physical findings, which makes it hard for physicians to recognize the problem and refer to rheumatology.
In the meantime, the longer it takes to diagnose psoriatic arthritis (PsA) and treat it properly, the worse off patients are when it’s finally caught. They “present with a greater rate of clinical progression and worse physical function, compared with patients with an undelayed diagnosis,” and more radiographic joint damage, according to investigators led by rheumatologist Alexis Ogdie, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia.
Dr. Ogdie’s study in BMC Rheumatology, and a second one from Arthritis Care & Research, both described the early phase of psoriatic arthritis, before formal diagnosis, to help with early recognition.
Delay associated with misdiagnosis
Dr. Ogdie’s team surveyed 203 adults with PsA – average age of 52 years, mostly white, and over 80% women – about their diagnosis history. The time between seeking medical attention for PsA-related symptoms and receiving a diagnosis was less than 6 months for 69 participants, 6 months to 4 years for 68, and 5 years or more for 66.
Typical symptoms, like joint pain, swollen joints, reduced range of motion, and dactylitis, were associated with quicker diagnosis. Turning early to dermatologists and rheumatologists – instead of general practitioners, orthopedics, chiropractors, and others – sped diagnosis, as well. People diagnosed within 6 months also tended to be slightly older, were less likely to be disabled or unemployed, have more education, and were more likely to make $100,000 per year or more.
Vaguer symptoms, such as stiffness, fatigue, and enthesitis-associated foot pain, delayed diagnosis. The longer PsA went unrecognized, the more likely people were to be misdiagnosed with osteoarthritis, psychosomatic disorders, and other problems.
“Increased recognition of heterogeneous symptoms associated with PsA, as well as understanding existing diagnostic barriers, may lead to prompt diagnosis and initiation of appropriate treatment that may improve outcomes,” the investigators concluded.
A prodromal phase
In the Arthritis Care & Research study, investigators led by Lihi Eder, MD, PhD, codirector of the cardio-rheumatology program at Women’s College Hospital, Toronto, used health records and databases to compare primary care histories of 462 Canadian PsA patients in the 5 years before they were diagnosed with 2,310 age- and sex-matched controls without PsA and treated by the same family physicians. The mean age in the study was 54 years, and just over half the subjects were women. Socioeconomic status and rurality were similar between the two groups.
The mean time from the initial primary care visit for a musculoskeletal complaint to rheumatology referral was 513 days among PsA patients, “which was substantially longer than for other inflammatory arthritic conditions, such as rheumatoid arthritis,” Dr. Eder and associates noted.
PsA patients were more than twice as likely to visit primary care for nonspecific musculoskeletal issues in the year before their diagnosis, and more likely in the 5 years prior. The odds of visits to musculoskeletal specialists, joint injections, joint imaging, and ED visits, was also higher as early as 5 years before PsA recognition, and hinted at the impending diagnosis.
“Our study characterized a prediagnosis period in PsA and supports the notion that a prodromal PsA phase occurs in a significant proportion of patients. ... This pattern reveals some of the underlying causes of diagnosis delays of PsA and highlights the need for diagnostic strategies and novel reliable biomarkers to aid in early diagnosis of PsA,” the investigators concluded.
Dr. Ogdie and colleagues suggested that community case searches, public awareness programs, patient education, and referral guidelines for primary care providers might help. They also suggested greater use of validated screening tools, such as the Psoriasis Epidemiology Screening Tool, in primary care.
Dr. Eder had no disclosures, and her study was funded by the Canadian Rheumatology Association. Dr. Ogdie’s study was funded by Novartis, maker of secukinumab (Cosentyx), which is indicated for PsA. She is a consultant for Novartis and has received grant support from the company. One author is an employee.
SOURCES: Ogdie A et al. BMC Rheumatol. 2020 Jan 10. doi: 10.1186/s41927-019-0102-7; Eder L et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24146.
FROM BMC RHEUMATOLOGY AND ARTHRITIS CARE & RESEARCH
Lidocaine-prilocaine cream tops lidocaine injections for vulvar biopsy pain
The median highest pain score in a randomized trial of 38 women undergoing vulvar biopsies was 25.7 mm lower, on a 100 mm visual analogue scale, when they received 5% lidocaine-prilocaine cream instead of a 1% lidocaine injection, according to a report from Duke University, in Durham, N.C.
“In the current study, we found that application of lidocaine-prilocaine cream, alone, for a minimum of 10 minutes before vulvar biopsy on a non–hair-bearing surface results in a significantly lower maximum pain score and a significantly better patient rating of the biopsy experience,” said investigators led by Logan K. Williams, MD, of the department of obstetrics and gynecology at Duke University, Durham, N.C.
Given the “clear advantage” of the cream, it “should be considered as an anesthetic method for vulvar biopsy in a non-hair-bearing area,” Dr. Williams and colleagues concluded (Obstet Gynecol. 2020 Feb;135{2]:311-8).
Studies have pitted the cream against the injection before, but they did not compare patients’ maximal pain scores. The team wanted to do that because “comparing the highest score allows us to consider the possibility that the pain of anesthesia application” – injection versus cream – “may be greater than the pain of any other portion of the biopsy procedure.”
They randomized 19 women to the cream, approximately 5 g at the site of biopsy at least 10 minutes beforehand, and 18 others to the injection, 2 mL using a 27-gauge needle, at least 1 minute prior.
The median highest pain score in the lidocaine-prilocaine group was 20 mm, but 56.5 mm in the injection group. Patients randomized to lidocaine-prilocaine also had a significantly better (P = 0.02) experience than those receiving injected lidocaine, also assessed by visual analog scale (VAS). The median baseline pain level was 0 mm.
Anxiety was assessed after patients knew whether they were going to get the cream or the injection, but before the biopsy. The median score in the cream group was of 19 mm on another VAS, compared with 31.5 mm.
Participants were 60 years old on average, and almost all had prior vulvar biopsies. Two in the cream group and three in the injection group had punch biopsies; cervical biopsy forceps were used for the rest. More than half the women had benign findings, and most of the others had vulvar intraepithelial neoplasia, but there was one invasive cancer. At Duke, the cost of the injection was $0.99, compared with $7.36 for the cream.
Dr. Williams and colleagues cited a few limitations. One is that the patients and clinicians in the study were not blinded. Another is that most of the patients had undergone vulvar biopsy before, possibly predisposing them to bias.
“In the future, consideration could be taken to studying lidocaine-prilocaine cream applications to hair-bearing surfaces, which were excluded in this study.” Also, “there is a question of the histologic effect of lidocaine-prilocaine on tissues and whether this could affect pathologic diagnoses.
“We are conducting a separate ancillary study in conjunction with our dermatopathology colleagues to investigate this question,” the investigators said.
The work was funded by Duke and the National Institutes of Health. Dr. Williams had no disclosures.
SOURCE: Williams LK et al. Obstet Gynecol. 2020 Feb;135(2):311-8.
The median highest pain score in a randomized trial of 38 women undergoing vulvar biopsies was 25.7 mm lower, on a 100 mm visual analogue scale, when they received 5% lidocaine-prilocaine cream instead of a 1% lidocaine injection, according to a report from Duke University, in Durham, N.C.
“In the current study, we found that application of lidocaine-prilocaine cream, alone, for a minimum of 10 minutes before vulvar biopsy on a non–hair-bearing surface results in a significantly lower maximum pain score and a significantly better patient rating of the biopsy experience,” said investigators led by Logan K. Williams, MD, of the department of obstetrics and gynecology at Duke University, Durham, N.C.
Given the “clear advantage” of the cream, it “should be considered as an anesthetic method for vulvar biopsy in a non-hair-bearing area,” Dr. Williams and colleagues concluded (Obstet Gynecol. 2020 Feb;135{2]:311-8).
Studies have pitted the cream against the injection before, but they did not compare patients’ maximal pain scores. The team wanted to do that because “comparing the highest score allows us to consider the possibility that the pain of anesthesia application” – injection versus cream – “may be greater than the pain of any other portion of the biopsy procedure.”
They randomized 19 women to the cream, approximately 5 g at the site of biopsy at least 10 minutes beforehand, and 18 others to the injection, 2 mL using a 27-gauge needle, at least 1 minute prior.
The median highest pain score in the lidocaine-prilocaine group was 20 mm, but 56.5 mm in the injection group. Patients randomized to lidocaine-prilocaine also had a significantly better (P = 0.02) experience than those receiving injected lidocaine, also assessed by visual analog scale (VAS). The median baseline pain level was 0 mm.
Anxiety was assessed after patients knew whether they were going to get the cream or the injection, but before the biopsy. The median score in the cream group was of 19 mm on another VAS, compared with 31.5 mm.
Participants were 60 years old on average, and almost all had prior vulvar biopsies. Two in the cream group and three in the injection group had punch biopsies; cervical biopsy forceps were used for the rest. More than half the women had benign findings, and most of the others had vulvar intraepithelial neoplasia, but there was one invasive cancer. At Duke, the cost of the injection was $0.99, compared with $7.36 for the cream.
Dr. Williams and colleagues cited a few limitations. One is that the patients and clinicians in the study were not blinded. Another is that most of the patients had undergone vulvar biopsy before, possibly predisposing them to bias.
“In the future, consideration could be taken to studying lidocaine-prilocaine cream applications to hair-bearing surfaces, which were excluded in this study.” Also, “there is a question of the histologic effect of lidocaine-prilocaine on tissues and whether this could affect pathologic diagnoses.
“We are conducting a separate ancillary study in conjunction with our dermatopathology colleagues to investigate this question,” the investigators said.
The work was funded by Duke and the National Institutes of Health. Dr. Williams had no disclosures.
SOURCE: Williams LK et al. Obstet Gynecol. 2020 Feb;135(2):311-8.
The median highest pain score in a randomized trial of 38 women undergoing vulvar biopsies was 25.7 mm lower, on a 100 mm visual analogue scale, when they received 5% lidocaine-prilocaine cream instead of a 1% lidocaine injection, according to a report from Duke University, in Durham, N.C.
“In the current study, we found that application of lidocaine-prilocaine cream, alone, for a minimum of 10 minutes before vulvar biopsy on a non–hair-bearing surface results in a significantly lower maximum pain score and a significantly better patient rating of the biopsy experience,” said investigators led by Logan K. Williams, MD, of the department of obstetrics and gynecology at Duke University, Durham, N.C.
Given the “clear advantage” of the cream, it “should be considered as an anesthetic method for vulvar biopsy in a non-hair-bearing area,” Dr. Williams and colleagues concluded (Obstet Gynecol. 2020 Feb;135{2]:311-8).
Studies have pitted the cream against the injection before, but they did not compare patients’ maximal pain scores. The team wanted to do that because “comparing the highest score allows us to consider the possibility that the pain of anesthesia application” – injection versus cream – “may be greater than the pain of any other portion of the biopsy procedure.”
They randomized 19 women to the cream, approximately 5 g at the site of biopsy at least 10 minutes beforehand, and 18 others to the injection, 2 mL using a 27-gauge needle, at least 1 minute prior.
The median highest pain score in the lidocaine-prilocaine group was 20 mm, but 56.5 mm in the injection group. Patients randomized to lidocaine-prilocaine also had a significantly better (P = 0.02) experience than those receiving injected lidocaine, also assessed by visual analog scale (VAS). The median baseline pain level was 0 mm.
Anxiety was assessed after patients knew whether they were going to get the cream or the injection, but before the biopsy. The median score in the cream group was of 19 mm on another VAS, compared with 31.5 mm.
Participants were 60 years old on average, and almost all had prior vulvar biopsies. Two in the cream group and three in the injection group had punch biopsies; cervical biopsy forceps were used for the rest. More than half the women had benign findings, and most of the others had vulvar intraepithelial neoplasia, but there was one invasive cancer. At Duke, the cost of the injection was $0.99, compared with $7.36 for the cream.
Dr. Williams and colleagues cited a few limitations. One is that the patients and clinicians in the study were not blinded. Another is that most of the patients had undergone vulvar biopsy before, possibly predisposing them to bias.
“In the future, consideration could be taken to studying lidocaine-prilocaine cream applications to hair-bearing surfaces, which were excluded in this study.” Also, “there is a question of the histologic effect of lidocaine-prilocaine on tissues and whether this could affect pathologic diagnoses.
“We are conducting a separate ancillary study in conjunction with our dermatopathology colleagues to investigate this question,” the investigators said.
The work was funded by Duke and the National Institutes of Health. Dr. Williams had no disclosures.
SOURCE: Williams LK et al. Obstet Gynecol. 2020 Feb;135(2):311-8.
FROM OBSTETRICS AND GYNECOLOGY
Fewer complications, better outcomes with outpatient UKA
according to a review from the University of Tennessee Campbell Clinic, Memphis.
“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.
He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.
They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.
“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.
There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.
It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.
The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”
Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m2 in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m2 in the inpatient group. The differences were not statistically significant.
No funding source was reported. The investigators did not report any disclosures.
SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001
according to a review from the University of Tennessee Campbell Clinic, Memphis.
“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.
He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.
They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.
“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.
There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.
It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.
The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”
Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m2 in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m2 in the inpatient group. The differences were not statistically significant.
No funding source was reported. The investigators did not report any disclosures.
SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001
according to a review from the University of Tennessee Campbell Clinic, Memphis.
“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.
He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.
They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.
“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.
There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.
It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.
The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”
Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m2 in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m2 in the inpatient group. The differences were not statistically significant.
No funding source was reported. The investigators did not report any disclosures.
SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001
FROM ORTHOPEDIC CLINICS OF NORTH AMERICA
CRISPR-engineered T cells may be safe for cancer, but do they work?
according to a report in Science.
The results of no harm support this “promising” area of cancer immunotherapy, according to study investigator Edward A. Stadtmauer, MD, of the University of Pennsylvania in Philadelphia and colleagues.
However, there was no evidence of benefit in this trial. One patient transfused with CRISPR-engineered T cells has since died, and the other two have moved on to other treatments.
“The big question that remains unanswered by this study is whether gene-edited, engineered T cells are effective against advanced cancer,” Jennifer Hamilton, PhD, and Jennifer Doudna, PhD, both of the University of California, Berkeley, wrote in an accompanying editorial.
The study enrolled six patients with refractory cancer, and three of them received CRISPR-engineered T cells. Two patients had multiple myeloma, and one had metastatic sarcoma.
Dr. Stadtmauer and colleagues drew blood from the patients, isolated the T cells, and used CRISPR-Cas9 to modify the cells. The T cells were transfected with Cas9 protein complexed with single guide RNAs against TRAC and TRBC (genes encoding the T-cell receptor chains TCR-alpha and TCR-beta) as well as PDCD1 (a gene encoding programmed cell death protein 1). The T cells were then transduced with a lentiviral vector to express a transgenic NY-ESO-1 cancer-specific T-cell receptor.
The investigators expanded the cell lines and infused them back into the patients after administering lymphodepleting chemotherapy. The sarcoma patient initially had a 50% decrease in a large abdominal mass, but all three patients ultimately progressed.
The editorialists noted that gene disruption efficiencies in this study were “modest,” ranging from 15% to 45%, but the investigators used a protocol from 2016, when the study was given the go-ahead by the National Institutes of Health and the Food and Drug Administration. With current protocols, gene disruption efficiencies can exceed 90%, which means patients might do better in subsequent trials.
There was no more than mild toxicity in this trial, and most adverse events were attributed to the lymphodepleting chemotherapy.
There was concern about potential rejection of infused cells because of preexisting immune responses to Cas9, but it doesn’t seem “to be a barrier to the application of this promising technology,” the investigators said.
They noted that “the stable engraftment of our engineered T cells is remarkably different from previously reported trials ... where the half-life of the cells in blood was [about] 1 week. Biopsy specimens of bone marrow in the myeloma patients and tumor in the sarcoma patient demonstrated trafficking of the engineered T cells to the tumor in all three patients” beyond that point. The decay half-life of the transduced cells was 20.3 days, 121.8 days, and 293.5 days in these patients.
The editorialists said the details in the report are a model for other researchers to follow, but “as more gene-based therapies are demonstrated to be safe and effective, the barrier to clinical translation will become cell manufacturing and administration.”
This work was funded by the National Institutes of Health and others. Dr. Stadtmauer didn’t report any disclosures, but other investigators disclosed patent applications and commercialization efforts. Dr. Doudna disclosed that she is a cofounder or adviser for several companies developing gene-editing therapeutics.
SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.
according to a report in Science.
The results of no harm support this “promising” area of cancer immunotherapy, according to study investigator Edward A. Stadtmauer, MD, of the University of Pennsylvania in Philadelphia and colleagues.
However, there was no evidence of benefit in this trial. One patient transfused with CRISPR-engineered T cells has since died, and the other two have moved on to other treatments.
“The big question that remains unanswered by this study is whether gene-edited, engineered T cells are effective against advanced cancer,” Jennifer Hamilton, PhD, and Jennifer Doudna, PhD, both of the University of California, Berkeley, wrote in an accompanying editorial.
The study enrolled six patients with refractory cancer, and three of them received CRISPR-engineered T cells. Two patients had multiple myeloma, and one had metastatic sarcoma.
Dr. Stadtmauer and colleagues drew blood from the patients, isolated the T cells, and used CRISPR-Cas9 to modify the cells. The T cells were transfected with Cas9 protein complexed with single guide RNAs against TRAC and TRBC (genes encoding the T-cell receptor chains TCR-alpha and TCR-beta) as well as PDCD1 (a gene encoding programmed cell death protein 1). The T cells were then transduced with a lentiviral vector to express a transgenic NY-ESO-1 cancer-specific T-cell receptor.
The investigators expanded the cell lines and infused them back into the patients after administering lymphodepleting chemotherapy. The sarcoma patient initially had a 50% decrease in a large abdominal mass, but all three patients ultimately progressed.
The editorialists noted that gene disruption efficiencies in this study were “modest,” ranging from 15% to 45%, but the investigators used a protocol from 2016, when the study was given the go-ahead by the National Institutes of Health and the Food and Drug Administration. With current protocols, gene disruption efficiencies can exceed 90%, which means patients might do better in subsequent trials.
There was no more than mild toxicity in this trial, and most adverse events were attributed to the lymphodepleting chemotherapy.
There was concern about potential rejection of infused cells because of preexisting immune responses to Cas9, but it doesn’t seem “to be a barrier to the application of this promising technology,” the investigators said.
They noted that “the stable engraftment of our engineered T cells is remarkably different from previously reported trials ... where the half-life of the cells in blood was [about] 1 week. Biopsy specimens of bone marrow in the myeloma patients and tumor in the sarcoma patient demonstrated trafficking of the engineered T cells to the tumor in all three patients” beyond that point. The decay half-life of the transduced cells was 20.3 days, 121.8 days, and 293.5 days in these patients.
The editorialists said the details in the report are a model for other researchers to follow, but “as more gene-based therapies are demonstrated to be safe and effective, the barrier to clinical translation will become cell manufacturing and administration.”
This work was funded by the National Institutes of Health and others. Dr. Stadtmauer didn’t report any disclosures, but other investigators disclosed patent applications and commercialization efforts. Dr. Doudna disclosed that she is a cofounder or adviser for several companies developing gene-editing therapeutics.
SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.
according to a report in Science.
The results of no harm support this “promising” area of cancer immunotherapy, according to study investigator Edward A. Stadtmauer, MD, of the University of Pennsylvania in Philadelphia and colleagues.
However, there was no evidence of benefit in this trial. One patient transfused with CRISPR-engineered T cells has since died, and the other two have moved on to other treatments.
“The big question that remains unanswered by this study is whether gene-edited, engineered T cells are effective against advanced cancer,” Jennifer Hamilton, PhD, and Jennifer Doudna, PhD, both of the University of California, Berkeley, wrote in an accompanying editorial.
The study enrolled six patients with refractory cancer, and three of them received CRISPR-engineered T cells. Two patients had multiple myeloma, and one had metastatic sarcoma.
Dr. Stadtmauer and colleagues drew blood from the patients, isolated the T cells, and used CRISPR-Cas9 to modify the cells. The T cells were transfected with Cas9 protein complexed with single guide RNAs against TRAC and TRBC (genes encoding the T-cell receptor chains TCR-alpha and TCR-beta) as well as PDCD1 (a gene encoding programmed cell death protein 1). The T cells were then transduced with a lentiviral vector to express a transgenic NY-ESO-1 cancer-specific T-cell receptor.
The investigators expanded the cell lines and infused them back into the patients after administering lymphodepleting chemotherapy. The sarcoma patient initially had a 50% decrease in a large abdominal mass, but all three patients ultimately progressed.
The editorialists noted that gene disruption efficiencies in this study were “modest,” ranging from 15% to 45%, but the investigators used a protocol from 2016, when the study was given the go-ahead by the National Institutes of Health and the Food and Drug Administration. With current protocols, gene disruption efficiencies can exceed 90%, which means patients might do better in subsequent trials.
There was no more than mild toxicity in this trial, and most adverse events were attributed to the lymphodepleting chemotherapy.
There was concern about potential rejection of infused cells because of preexisting immune responses to Cas9, but it doesn’t seem “to be a barrier to the application of this promising technology,” the investigators said.
They noted that “the stable engraftment of our engineered T cells is remarkably different from previously reported trials ... where the half-life of the cells in blood was [about] 1 week. Biopsy specimens of bone marrow in the myeloma patients and tumor in the sarcoma patient demonstrated trafficking of the engineered T cells to the tumor in all three patients” beyond that point. The decay half-life of the transduced cells was 20.3 days, 121.8 days, and 293.5 days in these patients.
The editorialists said the details in the report are a model for other researchers to follow, but “as more gene-based therapies are demonstrated to be safe and effective, the barrier to clinical translation will become cell manufacturing and administration.”
This work was funded by the National Institutes of Health and others. Dr. Stadtmauer didn’t report any disclosures, but other investigators disclosed patent applications and commercialization efforts. Dr. Doudna disclosed that she is a cofounder or adviser for several companies developing gene-editing therapeutics.
SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.
FROM SCIENCE
Staged hemispheric embolization: How to treat hemimegalencephaly within days of birth
BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.
The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.
A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.
Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.
Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.
At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.
The technique
In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.
Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.
After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.
“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.
Learning curve and outcomes
“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.
“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.
They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.
The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.
Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.
Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.
Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.
It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.
There was no funding, and the investigators didn’t have any relevant disclosures.
SOURCE: Chang T et al. AES 2019, Abstract 1.225.
BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.
The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.
A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.
Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.
Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.
At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.
The technique
In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.
Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.
After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.
“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.
Learning curve and outcomes
“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.
“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.
They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.
The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.
Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.
Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.
Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.
It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.
There was no funding, and the investigators didn’t have any relevant disclosures.
SOURCE: Chang T et al. AES 2019, Abstract 1.225.
BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.
The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.
A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.
Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.
Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.
At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.
The technique
In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.
Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.
After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.
“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.
Learning curve and outcomes
“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.
“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.
They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.
The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.
Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.
Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.
Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.
It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.
There was no funding, and the investigators didn’t have any relevant disclosures.
SOURCE: Chang T et al. AES 2019, Abstract 1.225.
REPORTING FROM AES 2019
RCT confirms CT scan screening catches lung cancer early
CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.
The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.
NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.
European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.
“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.
The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.
At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.
Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.
The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.
In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.
“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”
“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.
Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.
The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.
CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.
The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.
NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.
European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.
“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.
The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.
At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.
Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.
The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.
In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.
“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”
“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.
Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.
The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.
CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.
The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.
NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.
European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.
“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.
The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.
At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.
Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.
The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.
In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.
“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”
“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.
Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.
The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE