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Hospitalizations may speed up cognitive decline in older adults
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: Urgent or emergency admissions accelerated the rate of cognitive decline by 60%, compared with the prehospitalization rate. Elective admissions did not change the rate of cognitive decline.
Data source: The 930 patients were drawn from the Rush Memory and Aging Project.
Disclosures: The presenter had no financial disclosures.
Bowel prep score helps predict missed polyps
“Several recent prospective studies of one-time colonoscopies have demonstrated an association between higher BBPS (Boston Bowel Preparation Scale) scores and higher polyp and adenoma detection rates,” wrote Matthew A. Kluge, MD, of Boston University Medical Center, and his colleagues.
“We hypothesized that the BBPS could predict the likelihood of missed polyps based on initial BBPS segment scores among a large consortium of gastroenterology practices throughout the United States, thereby providing evidence to inform recommendations for repeat colonoscopy after less-than-perfect bowel preparation,” they said.
The researchers reviewed data from 335 pairs of colonoscopy exams in which the second exam (C2) was performed within 3 years of the first exam (C1). The primary endpoint was the detection of polyps and advanced polyps among colon segments at C2 stratified by BBPS scores at C1 (Gastrointest Endosc. 2017 Jun 22. doi: 10.1016/j.gie.2017.06.012).
Overall, patients with inadequate bowel prep were significantly more likely than those with adequate prep to be male (71% vs. 60%) and younger (average age, 59 years vs. 61 years). *
In a multivariate model, the risk of advanced polyps at C2 was significantly higher for patients who had advanced polyps at C1 (odds ratio, 3.5), but inadequate BBPS scores at C1 had no significant impact on advanced polyp risk at C2. The risk of advanced polyps at C2 increased slightly with each year of age (OR, 1.1), but was not impacted by sex or time between C1 and C2 visits.
In addition, polyps at C2 were significantly more likely in patients with inadequate examinations at C1 vs. adequate C1 exams (18% vs. 7%).
The study’s strengths include the use of a large database, but limitations include lack of information about pathology and the use of surrogate measures of polyp size, the researchers noted. However, the results highlight the importance of proper bowel prep and support previous observations that “individuals with a BBPS segment score of 0 and 1 may be at increased risk for missed polyps, especially if advanced polyps are detected,” they said.
The study was supported in part by the Clinical Outcomes Research Initiative (CORI) and by the National Institutes of Health, and CORI has received infrastructure support from companies including AstraZeneca, Bard International, Endosoft, Ethicon, GIVEN Imaging, Pentax USA, and ProVation. Lead author Dr. Kluge had no financial conflicts to disclose.
* This story was updated on 7/26/2017
“Several recent prospective studies of one-time colonoscopies have demonstrated an association between higher BBPS (Boston Bowel Preparation Scale) scores and higher polyp and adenoma detection rates,” wrote Matthew A. Kluge, MD, of Boston University Medical Center, and his colleagues.
“We hypothesized that the BBPS could predict the likelihood of missed polyps based on initial BBPS segment scores among a large consortium of gastroenterology practices throughout the United States, thereby providing evidence to inform recommendations for repeat colonoscopy after less-than-perfect bowel preparation,” they said.
The researchers reviewed data from 335 pairs of colonoscopy exams in which the second exam (C2) was performed within 3 years of the first exam (C1). The primary endpoint was the detection of polyps and advanced polyps among colon segments at C2 stratified by BBPS scores at C1 (Gastrointest Endosc. 2017 Jun 22. doi: 10.1016/j.gie.2017.06.012).
Overall, patients with inadequate bowel prep were significantly more likely than those with adequate prep to be male (71% vs. 60%) and younger (average age, 59 years vs. 61 years). *
In a multivariate model, the risk of advanced polyps at C2 was significantly higher for patients who had advanced polyps at C1 (odds ratio, 3.5), but inadequate BBPS scores at C1 had no significant impact on advanced polyp risk at C2. The risk of advanced polyps at C2 increased slightly with each year of age (OR, 1.1), but was not impacted by sex or time between C1 and C2 visits.
In addition, polyps at C2 were significantly more likely in patients with inadequate examinations at C1 vs. adequate C1 exams (18% vs. 7%).
The study’s strengths include the use of a large database, but limitations include lack of information about pathology and the use of surrogate measures of polyp size, the researchers noted. However, the results highlight the importance of proper bowel prep and support previous observations that “individuals with a BBPS segment score of 0 and 1 may be at increased risk for missed polyps, especially if advanced polyps are detected,” they said.
The study was supported in part by the Clinical Outcomes Research Initiative (CORI) and by the National Institutes of Health, and CORI has received infrastructure support from companies including AstraZeneca, Bard International, Endosoft, Ethicon, GIVEN Imaging, Pentax USA, and ProVation. Lead author Dr. Kluge had no financial conflicts to disclose.
* This story was updated on 7/26/2017
“Several recent prospective studies of one-time colonoscopies have demonstrated an association between higher BBPS (Boston Bowel Preparation Scale) scores and higher polyp and adenoma detection rates,” wrote Matthew A. Kluge, MD, of Boston University Medical Center, and his colleagues.
“We hypothesized that the BBPS could predict the likelihood of missed polyps based on initial BBPS segment scores among a large consortium of gastroenterology practices throughout the United States, thereby providing evidence to inform recommendations for repeat colonoscopy after less-than-perfect bowel preparation,” they said.
The researchers reviewed data from 335 pairs of colonoscopy exams in which the second exam (C2) was performed within 3 years of the first exam (C1). The primary endpoint was the detection of polyps and advanced polyps among colon segments at C2 stratified by BBPS scores at C1 (Gastrointest Endosc. 2017 Jun 22. doi: 10.1016/j.gie.2017.06.012).
Overall, patients with inadequate bowel prep were significantly more likely than those with adequate prep to be male (71% vs. 60%) and younger (average age, 59 years vs. 61 years). *
In a multivariate model, the risk of advanced polyps at C2 was significantly higher for patients who had advanced polyps at C1 (odds ratio, 3.5), but inadequate BBPS scores at C1 had no significant impact on advanced polyp risk at C2. The risk of advanced polyps at C2 increased slightly with each year of age (OR, 1.1), but was not impacted by sex or time between C1 and C2 visits.
In addition, polyps at C2 were significantly more likely in patients with inadequate examinations at C1 vs. adequate C1 exams (18% vs. 7%).
The study’s strengths include the use of a large database, but limitations include lack of information about pathology and the use of surrogate measures of polyp size, the researchers noted. However, the results highlight the importance of proper bowel prep and support previous observations that “individuals with a BBPS segment score of 0 and 1 may be at increased risk for missed polyps, especially if advanced polyps are detected,” they said.
The study was supported in part by the Clinical Outcomes Research Initiative (CORI) and by the National Institutes of Health, and CORI has received infrastructure support from companies including AstraZeneca, Bard International, Endosoft, Ethicon, GIVEN Imaging, Pentax USA, and ProVation. Lead author Dr. Kluge had no financial conflicts to disclose.
* This story was updated on 7/26/2017
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: Individuals with a score of 0 or 1 on the Boston Bowel Preparation Scale may be at increased risk for missed polyps.
Major finding: Polyps at a second colonoscopy were significantly more likely in patients who had advanced polyps at an initial visit (odds ratio, 3.5).
Data source: The data come from a prospective, observational study of adults aged 50-75 years who had average risk screening colonoscopies.
Disclosures: The study was supported in part by the Clinical Outcomes Research Initiative (CORI) and by the National Institutes of Health, and CORI has received infrastructure support from companies including AstraZeneca, Bard International, Endosoft, Ethicon, GIVEN Imaging, Pentax USA, and ProVation. Dr. Kluge had no financial conflicts to disclose.
Early neuroimaging essential for Zika-exposed neonates
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
FDA approves new treatment for adults with HCV
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.
Biceps Tenodesis: An Evolution of Treatment
Take-Home Points
- The LHB tendon has been shown to be a significant pain generator in the shoulder.
- At our institution, the number of LHB tenodeses significantly increased from 2004 to 2014.
- The age of patients who underwent a LHB tenodesis did not change significantly over the study period.
- Furthermore, the percentage of shoulder procedures that involved a LHB tenodesis significantly increased over the study period.
- Biceps tenodesis has become a more common procedure to treat shoulder pathology.
Although the exact function of the long head of the biceps (LHB) tendon is not completely understood, it is accepted that the LHB tendon can be a significant source of pain within the shoulder.1-4 Patients with symptoms related to biceps pathology often present with anterior shoulder pain that worsens with flexion and supination of the affected elbow and wrist.5 Although the sensitivity and specificity of physical examination maneuvers have been called into question, special tests have been developed to aid in the diagnosis of tendonitis of the LHB. These tests include the Speed, Yergason, bear hug, and uppercut tests as well as the O’Brien test (cross-body adduction).6,7 Recent studies have found LHB pathology in 45% of patients who undergo rotator cuff repair and in 63% of patients with a subscapularis tear.8,9
Pathology of the LHB tendon, including superior labrum anterior to posterior (SLAP) tears, can be treated in many ways.5,10,11 Options include SLAP repair, biceps tenodesis, débridement, and biceps tenotomy.11,12 Results of SLAP repairs have been less than optimal, but biceps tenodesis has been effective, and avoids the issue of cramping as can be seen with biceps tenotomy and débridement.10,12,13 Surgical methods for biceps tenodesis include open subpectoral and all-arthroscopic.11,12 Both methods have had good, reliable outcomes, but the all-arthroscopic technique is relatively new.11,12,14We conducted a study to determine LHB tenodesis trends, including patient age at time of surgery. We used surgical data from fellowship-trained sports or shoulder/elbow orthopedic surgeons at a busy subspecialty-based shoulder orthopedic practice. We hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis.
Methods
Our Institutional Review Board exempted this study. To determine the number of LHB tenodesis procedures performed at our institution, overall and in comparison with other common arthroscopic shoulder procedures, we queried the surgical database of 4 fellowship-trained orthopedic surgeons (shoulder/elbow, Drs. Nicholson and Cole; sports, Drs. Romeo and Verma) for the period January 1, 2004 to December 31, 2014. We used Current Procedural Terminology (CPT) code 23430 to determine the number of LHB tenodesis cases, as the surgeons primarily perform an open subpectoral biceps tenodesis. Patient age at time of surgery and the date of surgery were recorded. All patients who underwent LHB tenodesis between January 1, 2004 and December 31, 2014 were included. Number of procedures performed each year by each surgeon was recorded, as were concomitant procedures performed at the same time as the LHB tenodesis. To get the denominator (and reference point) for the number of arthroscopic shoulder surgeries performed by these 4 surgeons during the study period, and thereby determine the rate of LHB tenodesis, we selected the most common shoulder arthroscopy CPT codes used in our practice: 23430, 29806, 29807, 29822, 29823, 29825, 29826, and 29827. For a patient who underwent multiple procedures on the same day (multiple CPT codes entered on the same day), only one code was counted for that day. If 23430 was among the codes, it was included, and the case was placed in the numerator; if 23430 was not among the codes, the case was placed in the denominator.
The Arthroscopy Association of North America provides descriptions for the CPT codes: 23430 (tenodesis of long tendon of biceps), 29806 (arthroscopy, shoulder, surgical; capsulorrhaphy), 29807 (arthroscopy, shoulder, surgical; repair of SLAP lesion), 29822 (arthroscopy, shoulder, surgical; débridement, limited), 29823 (arthroscopy, shoulder, surgical; débridement, extensive), 29825 (arthroscopy, shoulder, surgical; with lysis and resection of adhesions, with or without manipulation), 29826 (arthroscopy, shoulder, surgical; decompression of subacromial space with partial acromioplasty, with or without coracoacromial release), and 29827 (arthroscopy, shoulder, surgical; with rotator cuff repair).
For analysis, we divided the data into total number of arthroscopic shoulder procedures performed by each surgeon each year and number of LHB tenodesis procedures performed by each surgeon each year. Total number of patients who had an arthroscopic procedure was used to create a denominator, and number of LHB tenodesis procedures showed the percentage of arthroscopic shoulder surgery patients who underwent LHB tenodesis. (All patients who undergo biceps tenodesis also have, at the least, diagnostic shoulder arthroscopy with or without tenotomy; if the tendon is ruptured, tenotomy is unnecessary.)
Descriptive statistics were calculated as means (SDs) for continuous variables and as frequencies with percentages for categorical variables. Linear regression analysis was used to determine whether the number of LHB tenodesis procedures changed during the study period and whether patient age changed over time. Significance was set at P < .05.
Results
Of the 7640 patients who underwent arthroscopic shoulder procedures between 2004 and 2014, 2125 had LHB tenodesis (CPT code 23430). 
Discussion
Tenodesis has become a common treatment option for several pathologic shoulder conditions involving the LHB tendon.5 We set out to determine trends in LHB tenodesis at a subspecialty-focused shoulder orthopedic practice and hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis. Our hypotheses were confirmed: The number of LHB tenodesis cases increased significantly without a significant change in patient age.
Treatment options for LHB pathology and SLAP tears include simple tenotomy, débridement, open biceps tenodesis, and arthroscopic tenodesis.11,12,15
Recent evidence has called into question the results of SLAP repairs and suggested biceps tenodesis may be a better treatment option for SLAP tears.10,13,21 Studies have found excellent outcomes with open subpectoral biceps tenodesis in the treatment of SLAP tears, and others have found better restoration of pitchers’ thoracic rotation with open subpectoral biceps tenodesis than with SLAP repair.13,14 Similarly, comparison studies have largely favored biceps tenodesis over SLAP repair, particularly in patients older than 35 years to 40 years.22 Given these results, it is not surprising that, querying the American Board of Orthopaedic Surgeons (ABOS) part II database for isolated SLAP lesions treated between 2002 and 2011, Patterson and colleagues23 found the percentage of SLAP repairs decreased from 69.3% to 44.8% (P < .0001), whereas the percentage of biceps tenodesis procedures increased from 1.9% to 18.8% (P < .0001), indicating the realization of improved outcomes with LHB tenodesis in the treatment of SLAP tears. On the other hand, in the ABOS part II database for the period 2003 to 2008, Weber and colleagues24 found that, despite a decrease in the percentage of SLAP repairs, total number of SLAP repairs increased from 9.4% to 10.1% (P = .0163). According to our study results, the number of SLAP repairs is decreasing over time, whereas the number of LHB tenodesis procedures is continuing to rise. The practice patterns seen in our study correlate with those in previous studies of the treatment of SLAP tears: good results in tenodesis groups and poor results in SLAP repair groups.10,13Werner and colleagues25 recently used the large PearlDiver database, which includes information from both private payers and Medicare, to determine overall LHB tenodesis trends in the United States for the period 2008 to 2011. Over those years, the incidence of LHB tenodesis increased 1.7-fold, and the rate of arthroscopic LHB tenodesis increased significantly more than the rate of open LHB tenodesis. These results are similar to ours in that the number of LHB tenodesis cases increased significantly over time. However, as the overwhelming majority of patients in our practice undergo open biceps tenodesis, the faster rate of growth in the arthroscopic cohort relative to the open cohort cannot be assessed. Additional randomized studies comparing biceps tenodesis, both open and arthroscopic, with SLAP repair are needed to properly determine the superiority of LHB tenodesis over SLAP repair.
One strength of this database study was the number of patients: more than 7000, 2125 of whom underwent biceps tenodesis performed by 1 of 4 fellowship-trained orthopedic surgeons. There were several study limitations. First, because the original diagnoses were not recorded, it was unclear exactly which pathologies were treated with tenodesis, limiting our ability to make recommendations regarding treatment trends for specific pathologies. Similarly, we did not assess outcome variables, which would have allowed us to draw conclusions about the effectiveness of the biceps tenodesis procedures. Furthermore, some procedures may have been coded incorrectly, and therefore some patients may have been erroneously included or excluded. In addition, using data from only one institution may have introduced bias into our conclusions, though the results are consistent with national trends. Finally, there was some variability among the 4 surgeons in the number of LHB tenodesis procedures performed, and this variability may have confounded results, though these surgeons treat biceps pathology in similar ways.
Am J Orthop. 2017;46(4):E219-E223. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Denard PJ, Dai X, Hanypsiak BT, Burkhart SS. Anatomy of the biceps tendon: implications for restoring physiological length–tension relation during biceps tenodesis with interference screw fixation. Arthroscopy. 2012;28(10):1352-1358.
2. Ejnisman B, Monteiro GC, Andreoli CV, de Castro Pochini A. Disorder of the long head of the biceps tendon. Br J Sports Med. 2010;44(5):347-354.
3. Mellano CR, Shin JJ, Yanke AB, Verma NN. Disorders of the long head of the biceps tendon. Instr Course Lect. 2015;64:567-576.
4. Szabo I, Boileau P, Walch G. The proximal biceps as a pain generator and results of tenotomy. Sports Med Arthrosc Rev. 2008;16(3):180-186.
5. Harwin SF, Birns ME, Mbabuike JJ, Porter DA, Galano GJ. Arthroscopic tenodesis of the long head of the biceps. Orthopedics. 2014;37(11):743-747.
6. Holtby R, Razmjou H. Accuracy of the Speed’s and Yergason’s tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings. Arthroscopy. 2004;20(3):231-236.
7. Ben Kibler W, Sciascia AD, Hester P, Dome D, Jacobs C. Clinical utility of traditional and new tests in the diagnosis of biceps tendon injuries and superior labrum anterior and posterior lesions in the shoulder. Am J Sports Med. 2009;37(9):1840-1847.
8. Lafosse L, Reiland Y, Baier GP, Toussaint B, Jost B. Anterior and posterior instability of the long head of the biceps tendon in rotator cuff tears: a new classification based on arthroscopic observations. Arthroscopy. 2007;23(1):73-80.
9. Adams CR, Schoolfield JD, Burkhart SS. The results of arthroscopic subscapularis tendon repairs. Arthroscopy. 2008;24(12):1381-1389.
10. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.
11. Gombera MM, Kahlenberg CA, Nair R, Saltzman MD, Terry MA. All-arthroscopic suprapectoral versus open subpectoral tenodesis of the long head of the biceps brachii. Am J Sports Med. 2015;43(5):1077-1083.
12. Delle Rose G, Borroni M, Silvestro A, et al. The long head of biceps as a source of pain in active population: tenotomy or tenodesis? A comparison of 2 case series with isolated lesions. Musculoskelet Surg. 2012;96(suppl 1):S47-S52.
13. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.
14. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.
15. Ge H, Zhang Q, Sun Y, Li J, Sun L, Cheng B. Tenotomy or tenodesis for the long head of biceps lesions in shoulders: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0121286.
16. Kaback LA, Gowda AL, Paller D, Green A, Blaine T. Long head biceps tenodesis with a knotless cinch suture anchor: a biomechanical analysis. Arthroscopy. 2015;31(5):831-835.
17. Kany J, Guinand R, Amaravathi RS, Alassaf I. The keyhole technique for arthroscopic tenodesis of the long head of the biceps tendon. In vivo prospective study with a radio-opaque marker. Orthop Traumatol Surg Res. 2015;101(1):31-34.
18. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
19. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc Rev. 2008;16(3):170-176.
20. Erickson BJ, Jain A, Abrams GD, et al. SLAP lesions: trends in treatment. Arthroscopy. 2016;32(6):976-981.
21. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.
22. Denard PJ, Ladermann A, Parsley BK, Burkhart SS. Arthroscopic biceps tenodesis compared with repair of isolated type II SLAP lesions in patients older than 35 years. Orthopedics. 2014;37(3):e292-e297.
23. Patterson BM, Creighton RA, Spang JT, Roberson JR, Kamath GV. Surgical trends in the treatment of superior labrum anterior and posterior lesions of the shoulder: analysis of data from the American Board of Orthopaedic Surgery certification examination database. Am J Sports Med. 2014;42(8):1904-1910.
24. Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.
25. Werner BC, Brockmeier SF, Gwathmey FW. Trends in long head biceps tenodesis. Am J Sports Med. 2015;43(3):570-578.
Take-Home Points
- The LHB tendon has been shown to be a significant pain generator in the shoulder.
- At our institution, the number of LHB tenodeses significantly increased from 2004 to 2014.
- The age of patients who underwent a LHB tenodesis did not change significantly over the study period.
- Furthermore, the percentage of shoulder procedures that involved a LHB tenodesis significantly increased over the study period.
- Biceps tenodesis has become a more common procedure to treat shoulder pathology.
Although the exact function of the long head of the biceps (LHB) tendon is not completely understood, it is accepted that the LHB tendon can be a significant source of pain within the shoulder.1-4 Patients with symptoms related to biceps pathology often present with anterior shoulder pain that worsens with flexion and supination of the affected elbow and wrist.5 Although the sensitivity and specificity of physical examination maneuvers have been called into question, special tests have been developed to aid in the diagnosis of tendonitis of the LHB. These tests include the Speed, Yergason, bear hug, and uppercut tests as well as the O’Brien test (cross-body adduction).6,7 Recent studies have found LHB pathology in 45% of patients who undergo rotator cuff repair and in 63% of patients with a subscapularis tear.8,9
Pathology of the LHB tendon, including superior labrum anterior to posterior (SLAP) tears, can be treated in many ways.5,10,11 Options include SLAP repair, biceps tenodesis, débridement, and biceps tenotomy.11,12 Results of SLAP repairs have been less than optimal, but biceps tenodesis has been effective, and avoids the issue of cramping as can be seen with biceps tenotomy and débridement.10,12,13 Surgical methods for biceps tenodesis include open subpectoral and all-arthroscopic.11,12 Both methods have had good, reliable outcomes, but the all-arthroscopic technique is relatively new.11,12,14We conducted a study to determine LHB tenodesis trends, including patient age at time of surgery. We used surgical data from fellowship-trained sports or shoulder/elbow orthopedic surgeons at a busy subspecialty-based shoulder orthopedic practice. We hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis.
Methods
Our Institutional Review Board exempted this study. To determine the number of LHB tenodesis procedures performed at our institution, overall and in comparison with other common arthroscopic shoulder procedures, we queried the surgical database of 4 fellowship-trained orthopedic surgeons (shoulder/elbow, Drs. Nicholson and Cole; sports, Drs. Romeo and Verma) for the period January 1, 2004 to December 31, 2014. We used Current Procedural Terminology (CPT) code 23430 to determine the number of LHB tenodesis cases, as the surgeons primarily perform an open subpectoral biceps tenodesis. Patient age at time of surgery and the date of surgery were recorded. All patients who underwent LHB tenodesis between January 1, 2004 and December 31, 2014 were included. Number of procedures performed each year by each surgeon was recorded, as were concomitant procedures performed at the same time as the LHB tenodesis. To get the denominator (and reference point) for the number of arthroscopic shoulder surgeries performed by these 4 surgeons during the study period, and thereby determine the rate of LHB tenodesis, we selected the most common shoulder arthroscopy CPT codes used in our practice: 23430, 29806, 29807, 29822, 29823, 29825, 29826, and 29827. For a patient who underwent multiple procedures on the same day (multiple CPT codes entered on the same day), only one code was counted for that day. If 23430 was among the codes, it was included, and the case was placed in the numerator; if 23430 was not among the codes, the case was placed in the denominator.
The Arthroscopy Association of North America provides descriptions for the CPT codes: 23430 (tenodesis of long tendon of biceps), 29806 (arthroscopy, shoulder, surgical; capsulorrhaphy), 29807 (arthroscopy, shoulder, surgical; repair of SLAP lesion), 29822 (arthroscopy, shoulder, surgical; débridement, limited), 29823 (arthroscopy, shoulder, surgical; débridement, extensive), 29825 (arthroscopy, shoulder, surgical; with lysis and resection of adhesions, with or without manipulation), 29826 (arthroscopy, shoulder, surgical; decompression of subacromial space with partial acromioplasty, with or without coracoacromial release), and 29827 (arthroscopy, shoulder, surgical; with rotator cuff repair).
For analysis, we divided the data into total number of arthroscopic shoulder procedures performed by each surgeon each year and number of LHB tenodesis procedures performed by each surgeon each year. Total number of patients who had an arthroscopic procedure was used to create a denominator, and number of LHB tenodesis procedures showed the percentage of arthroscopic shoulder surgery patients who underwent LHB tenodesis. (All patients who undergo biceps tenodesis also have, at the least, diagnostic shoulder arthroscopy with or without tenotomy; if the tendon is ruptured, tenotomy is unnecessary.)
Descriptive statistics were calculated as means (SDs) for continuous variables and as frequencies with percentages for categorical variables. Linear regression analysis was used to determine whether the number of LHB tenodesis procedures changed during the study period and whether patient age changed over time. Significance was set at P < .05.
Results
Of the 7640 patients who underwent arthroscopic shoulder procedures between 2004 and 2014, 2125 had LHB tenodesis (CPT code 23430).
Discussion
Tenodesis has become a common treatment option for several pathologic shoulder conditions involving the LHB tendon.5 We set out to determine trends in LHB tenodesis at a subspecialty-focused shoulder orthopedic practice and hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis. Our hypotheses were confirmed: The number of LHB tenodesis cases increased significantly without a significant change in patient age.
Treatment options for LHB pathology and SLAP tears include simple tenotomy, débridement, open biceps tenodesis, and arthroscopic tenodesis.11,12,15
Recent evidence has called into question the results of SLAP repairs and suggested biceps tenodesis may be a better treatment option for SLAP tears.10,13,21 Studies have found excellent outcomes with open subpectoral biceps tenodesis in the treatment of SLAP tears, and others have found better restoration of pitchers’ thoracic rotation with open subpectoral biceps tenodesis than with SLAP repair.13,14 Similarly, comparison studies have largely favored biceps tenodesis over SLAP repair, particularly in patients older than 35 years to 40 years.22 Given these results, it is not surprising that, querying the American Board of Orthopaedic Surgeons (ABOS) part II database for isolated SLAP lesions treated between 2002 and 2011, Patterson and colleagues23 found the percentage of SLAP repairs decreased from 69.3% to 44.8% (P < .0001), whereas the percentage of biceps tenodesis procedures increased from 1.9% to 18.8% (P < .0001), indicating the realization of improved outcomes with LHB tenodesis in the treatment of SLAP tears. On the other hand, in the ABOS part II database for the period 2003 to 2008, Weber and colleagues24 found that, despite a decrease in the percentage of SLAP repairs, total number of SLAP repairs increased from 9.4% to 10.1% (P = .0163). According to our study results, the number of SLAP repairs is decreasing over time, whereas the number of LHB tenodesis procedures is continuing to rise. The practice patterns seen in our study correlate with those in previous studies of the treatment of SLAP tears: good results in tenodesis groups and poor results in SLAP repair groups.10,13Werner and colleagues25 recently used the large PearlDiver database, which includes information from both private payers and Medicare, to determine overall LHB tenodesis trends in the United States for the period 2008 to 2011. Over those years, the incidence of LHB tenodesis increased 1.7-fold, and the rate of arthroscopic LHB tenodesis increased significantly more than the rate of open LHB tenodesis. These results are similar to ours in that the number of LHB tenodesis cases increased significantly over time. However, as the overwhelming majority of patients in our practice undergo open biceps tenodesis, the faster rate of growth in the arthroscopic cohort relative to the open cohort cannot be assessed. Additional randomized studies comparing biceps tenodesis, both open and arthroscopic, with SLAP repair are needed to properly determine the superiority of LHB tenodesis over SLAP repair.
One strength of this database study was the number of patients: more than 7000, 2125 of whom underwent biceps tenodesis performed by 1 of 4 fellowship-trained orthopedic surgeons. There were several study limitations. First, because the original diagnoses were not recorded, it was unclear exactly which pathologies were treated with tenodesis, limiting our ability to make recommendations regarding treatment trends for specific pathologies. Similarly, we did not assess outcome variables, which would have allowed us to draw conclusions about the effectiveness of the biceps tenodesis procedures. Furthermore, some procedures may have been coded incorrectly, and therefore some patients may have been erroneously included or excluded. In addition, using data from only one institution may have introduced bias into our conclusions, though the results are consistent with national trends. Finally, there was some variability among the 4 surgeons in the number of LHB tenodesis procedures performed, and this variability may have confounded results, though these surgeons treat biceps pathology in similar ways.
Am J Orthop. 2017;46(4):E219-E223. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
Take-Home Points
- The LHB tendon has been shown to be a significant pain generator in the shoulder.
- At our institution, the number of LHB tenodeses significantly increased from 2004 to 2014.
- The age of patients who underwent a LHB tenodesis did not change significantly over the study period.
- Furthermore, the percentage of shoulder procedures that involved a LHB tenodesis significantly increased over the study period.
- Biceps tenodesis has become a more common procedure to treat shoulder pathology.
Although the exact function of the long head of the biceps (LHB) tendon is not completely understood, it is accepted that the LHB tendon can be a significant source of pain within the shoulder.1-4 Patients with symptoms related to biceps pathology often present with anterior shoulder pain that worsens with flexion and supination of the affected elbow and wrist.5 Although the sensitivity and specificity of physical examination maneuvers have been called into question, special tests have been developed to aid in the diagnosis of tendonitis of the LHB. These tests include the Speed, Yergason, bear hug, and uppercut tests as well as the O’Brien test (cross-body adduction).6,7 Recent studies have found LHB pathology in 45% of patients who undergo rotator cuff repair and in 63% of patients with a subscapularis tear.8,9
Pathology of the LHB tendon, including superior labrum anterior to posterior (SLAP) tears, can be treated in many ways.5,10,11 Options include SLAP repair, biceps tenodesis, débridement, and biceps tenotomy.11,12 Results of SLAP repairs have been less than optimal, but biceps tenodesis has been effective, and avoids the issue of cramping as can be seen with biceps tenotomy and débridement.10,12,13 Surgical methods for biceps tenodesis include open subpectoral and all-arthroscopic.11,12 Both methods have had good, reliable outcomes, but the all-arthroscopic technique is relatively new.11,12,14We conducted a study to determine LHB tenodesis trends, including patient age at time of surgery. We used surgical data from fellowship-trained sports or shoulder/elbow orthopedic surgeons at a busy subspecialty-based shoulder orthopedic practice. We hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis.
Methods
Our Institutional Review Board exempted this study. To determine the number of LHB tenodesis procedures performed at our institution, overall and in comparison with other common arthroscopic shoulder procedures, we queried the surgical database of 4 fellowship-trained orthopedic surgeons (shoulder/elbow, Drs. Nicholson and Cole; sports, Drs. Romeo and Verma) for the period January 1, 2004 to December 31, 2014. We used Current Procedural Terminology (CPT) code 23430 to determine the number of LHB tenodesis cases, as the surgeons primarily perform an open subpectoral biceps tenodesis. Patient age at time of surgery and the date of surgery were recorded. All patients who underwent LHB tenodesis between January 1, 2004 and December 31, 2014 were included. Number of procedures performed each year by each surgeon was recorded, as were concomitant procedures performed at the same time as the LHB tenodesis. To get the denominator (and reference point) for the number of arthroscopic shoulder surgeries performed by these 4 surgeons during the study period, and thereby determine the rate of LHB tenodesis, we selected the most common shoulder arthroscopy CPT codes used in our practice: 23430, 29806, 29807, 29822, 29823, 29825, 29826, and 29827. For a patient who underwent multiple procedures on the same day (multiple CPT codes entered on the same day), only one code was counted for that day. If 23430 was among the codes, it was included, and the case was placed in the numerator; if 23430 was not among the codes, the case was placed in the denominator.
The Arthroscopy Association of North America provides descriptions for the CPT codes: 23430 (tenodesis of long tendon of biceps), 29806 (arthroscopy, shoulder, surgical; capsulorrhaphy), 29807 (arthroscopy, shoulder, surgical; repair of SLAP lesion), 29822 (arthroscopy, shoulder, surgical; débridement, limited), 29823 (arthroscopy, shoulder, surgical; débridement, extensive), 29825 (arthroscopy, shoulder, surgical; with lysis and resection of adhesions, with or without manipulation), 29826 (arthroscopy, shoulder, surgical; decompression of subacromial space with partial acromioplasty, with or without coracoacromial release), and 29827 (arthroscopy, shoulder, surgical; with rotator cuff repair).
For analysis, we divided the data into total number of arthroscopic shoulder procedures performed by each surgeon each year and number of LHB tenodesis procedures performed by each surgeon each year. Total number of patients who had an arthroscopic procedure was used to create a denominator, and number of LHB tenodesis procedures showed the percentage of arthroscopic shoulder surgery patients who underwent LHB tenodesis. (All patients who undergo biceps tenodesis also have, at the least, diagnostic shoulder arthroscopy with or without tenotomy; if the tendon is ruptured, tenotomy is unnecessary.)
Descriptive statistics were calculated as means (SDs) for continuous variables and as frequencies with percentages for categorical variables. Linear regression analysis was used to determine whether the number of LHB tenodesis procedures changed during the study period and whether patient age changed over time. Significance was set at P < .05.
Results
Of the 7640 patients who underwent arthroscopic shoulder procedures between 2004 and 2014, 2125 had LHB tenodesis (CPT code 23430).
Discussion
Tenodesis has become a common treatment option for several pathologic shoulder conditions involving the LHB tendon.5 We set out to determine trends in LHB tenodesis at a subspecialty-focused shoulder orthopedic practice and hypothesized that the rate of LHB tenodesis would increase significantly over time and that there would be no significant change in the age of patients who underwent LHB tenodesis. Our hypotheses were confirmed: The number of LHB tenodesis cases increased significantly without a significant change in patient age.
Treatment options for LHB pathology and SLAP tears include simple tenotomy, débridement, open biceps tenodesis, and arthroscopic tenodesis.11,12,15
Recent evidence has called into question the results of SLAP repairs and suggested biceps tenodesis may be a better treatment option for SLAP tears.10,13,21 Studies have found excellent outcomes with open subpectoral biceps tenodesis in the treatment of SLAP tears, and others have found better restoration of pitchers’ thoracic rotation with open subpectoral biceps tenodesis than with SLAP repair.13,14 Similarly, comparison studies have largely favored biceps tenodesis over SLAP repair, particularly in patients older than 35 years to 40 years.22 Given these results, it is not surprising that, querying the American Board of Orthopaedic Surgeons (ABOS) part II database for isolated SLAP lesions treated between 2002 and 2011, Patterson and colleagues23 found the percentage of SLAP repairs decreased from 69.3% to 44.8% (P < .0001), whereas the percentage of biceps tenodesis procedures increased from 1.9% to 18.8% (P < .0001), indicating the realization of improved outcomes with LHB tenodesis in the treatment of SLAP tears. On the other hand, in the ABOS part II database for the period 2003 to 2008, Weber and colleagues24 found that, despite a decrease in the percentage of SLAP repairs, total number of SLAP repairs increased from 9.4% to 10.1% (P = .0163). According to our study results, the number of SLAP repairs is decreasing over time, whereas the number of LHB tenodesis procedures is continuing to rise. The practice patterns seen in our study correlate with those in previous studies of the treatment of SLAP tears: good results in tenodesis groups and poor results in SLAP repair groups.10,13Werner and colleagues25 recently used the large PearlDiver database, which includes information from both private payers and Medicare, to determine overall LHB tenodesis trends in the United States for the period 2008 to 2011. Over those years, the incidence of LHB tenodesis increased 1.7-fold, and the rate of arthroscopic LHB tenodesis increased significantly more than the rate of open LHB tenodesis. These results are similar to ours in that the number of LHB tenodesis cases increased significantly over time. However, as the overwhelming majority of patients in our practice undergo open biceps tenodesis, the faster rate of growth in the arthroscopic cohort relative to the open cohort cannot be assessed. Additional randomized studies comparing biceps tenodesis, both open and arthroscopic, with SLAP repair are needed to properly determine the superiority of LHB tenodesis over SLAP repair.
One strength of this database study was the number of patients: more than 7000, 2125 of whom underwent biceps tenodesis performed by 1 of 4 fellowship-trained orthopedic surgeons. There were several study limitations. First, because the original diagnoses were not recorded, it was unclear exactly which pathologies were treated with tenodesis, limiting our ability to make recommendations regarding treatment trends for specific pathologies. Similarly, we did not assess outcome variables, which would have allowed us to draw conclusions about the effectiveness of the biceps tenodesis procedures. Furthermore, some procedures may have been coded incorrectly, and therefore some patients may have been erroneously included or excluded. In addition, using data from only one institution may have introduced bias into our conclusions, though the results are consistent with national trends. Finally, there was some variability among the 4 surgeons in the number of LHB tenodesis procedures performed, and this variability may have confounded results, though these surgeons treat biceps pathology in similar ways.
Am J Orthop. 2017;46(4):E219-E223. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Denard PJ, Dai X, Hanypsiak BT, Burkhart SS. Anatomy of the biceps tendon: implications for restoring physiological length–tension relation during biceps tenodesis with interference screw fixation. Arthroscopy. 2012;28(10):1352-1358.
2. Ejnisman B, Monteiro GC, Andreoli CV, de Castro Pochini A. Disorder of the long head of the biceps tendon. Br J Sports Med. 2010;44(5):347-354.
3. Mellano CR, Shin JJ, Yanke AB, Verma NN. Disorders of the long head of the biceps tendon. Instr Course Lect. 2015;64:567-576.
4. Szabo I, Boileau P, Walch G. The proximal biceps as a pain generator and results of tenotomy. Sports Med Arthrosc Rev. 2008;16(3):180-186.
5. Harwin SF, Birns ME, Mbabuike JJ, Porter DA, Galano GJ. Arthroscopic tenodesis of the long head of the biceps. Orthopedics. 2014;37(11):743-747.
6. Holtby R, Razmjou H. Accuracy of the Speed’s and Yergason’s tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings. Arthroscopy. 2004;20(3):231-236.
7. Ben Kibler W, Sciascia AD, Hester P, Dome D, Jacobs C. Clinical utility of traditional and new tests in the diagnosis of biceps tendon injuries and superior labrum anterior and posterior lesions in the shoulder. Am J Sports Med. 2009;37(9):1840-1847.
8. Lafosse L, Reiland Y, Baier GP, Toussaint B, Jost B. Anterior and posterior instability of the long head of the biceps tendon in rotator cuff tears: a new classification based on arthroscopic observations. Arthroscopy. 2007;23(1):73-80.
9. Adams CR, Schoolfield JD, Burkhart SS. The results of arthroscopic subscapularis tendon repairs. Arthroscopy. 2008;24(12):1381-1389.
10. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.
11. Gombera MM, Kahlenberg CA, Nair R, Saltzman MD, Terry MA. All-arthroscopic suprapectoral versus open subpectoral tenodesis of the long head of the biceps brachii. Am J Sports Med. 2015;43(5):1077-1083.
12. Delle Rose G, Borroni M, Silvestro A, et al. The long head of biceps as a source of pain in active population: tenotomy or tenodesis? A comparison of 2 case series with isolated lesions. Musculoskelet Surg. 2012;96(suppl 1):S47-S52.
13. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.
14. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.
15. Ge H, Zhang Q, Sun Y, Li J, Sun L, Cheng B. Tenotomy or tenodesis for the long head of biceps lesions in shoulders: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0121286.
16. Kaback LA, Gowda AL, Paller D, Green A, Blaine T. Long head biceps tenodesis with a knotless cinch suture anchor: a biomechanical analysis. Arthroscopy. 2015;31(5):831-835.
17. Kany J, Guinand R, Amaravathi RS, Alassaf I. The keyhole technique for arthroscopic tenodesis of the long head of the biceps tendon. In vivo prospective study with a radio-opaque marker. Orthop Traumatol Surg Res. 2015;101(1):31-34.
18. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
19. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc Rev. 2008;16(3):170-176.
20. Erickson BJ, Jain A, Abrams GD, et al. SLAP lesions: trends in treatment. Arthroscopy. 2016;32(6):976-981.
21. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.
22. Denard PJ, Ladermann A, Parsley BK, Burkhart SS. Arthroscopic biceps tenodesis compared with repair of isolated type II SLAP lesions in patients older than 35 years. Orthopedics. 2014;37(3):e292-e297.
23. Patterson BM, Creighton RA, Spang JT, Roberson JR, Kamath GV. Surgical trends in the treatment of superior labrum anterior and posterior lesions of the shoulder: analysis of data from the American Board of Orthopaedic Surgery certification examination database. Am J Sports Med. 2014;42(8):1904-1910.
24. Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.
25. Werner BC, Brockmeier SF, Gwathmey FW. Trends in long head biceps tenodesis. Am J Sports Med. 2015;43(3):570-578.
1. Denard PJ, Dai X, Hanypsiak BT, Burkhart SS. Anatomy of the biceps tendon: implications for restoring physiological length–tension relation during biceps tenodesis with interference screw fixation. Arthroscopy. 2012;28(10):1352-1358.
2. Ejnisman B, Monteiro GC, Andreoli CV, de Castro Pochini A. Disorder of the long head of the biceps tendon. Br J Sports Med. 2010;44(5):347-354.
3. Mellano CR, Shin JJ, Yanke AB, Verma NN. Disorders of the long head of the biceps tendon. Instr Course Lect. 2015;64:567-576.
4. Szabo I, Boileau P, Walch G. The proximal biceps as a pain generator and results of tenotomy. Sports Med Arthrosc Rev. 2008;16(3):180-186.
5. Harwin SF, Birns ME, Mbabuike JJ, Porter DA, Galano GJ. Arthroscopic tenodesis of the long head of the biceps. Orthopedics. 2014;37(11):743-747.
6. Holtby R, Razmjou H. Accuracy of the Speed’s and Yergason’s tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings. Arthroscopy. 2004;20(3):231-236.
7. Ben Kibler W, Sciascia AD, Hester P, Dome D, Jacobs C. Clinical utility of traditional and new tests in the diagnosis of biceps tendon injuries and superior labrum anterior and posterior lesions in the shoulder. Am J Sports Med. 2009;37(9):1840-1847.
8. Lafosse L, Reiland Y, Baier GP, Toussaint B, Jost B. Anterior and posterior instability of the long head of the biceps tendon in rotator cuff tears: a new classification based on arthroscopic observations. Arthroscopy. 2007;23(1):73-80.
9. Adams CR, Schoolfield JD, Burkhart SS. The results of arthroscopic subscapularis tendon repairs. Arthroscopy. 2008;24(12):1381-1389.
10. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.
11. Gombera MM, Kahlenberg CA, Nair R, Saltzman MD, Terry MA. All-arthroscopic suprapectoral versus open subpectoral tenodesis of the long head of the biceps brachii. Am J Sports Med. 2015;43(5):1077-1083.
12. Delle Rose G, Borroni M, Silvestro A, et al. The long head of biceps as a source of pain in active population: tenotomy or tenodesis? A comparison of 2 case series with isolated lesions. Musculoskelet Surg. 2012;96(suppl 1):S47-S52.
13. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.
14. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.
15. Ge H, Zhang Q, Sun Y, Li J, Sun L, Cheng B. Tenotomy or tenodesis for the long head of biceps lesions in shoulders: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0121286.
16. Kaback LA, Gowda AL, Paller D, Green A, Blaine T. Long head biceps tenodesis with a knotless cinch suture anchor: a biomechanical analysis. Arthroscopy. 2015;31(5):831-835.
17. Kany J, Guinand R, Amaravathi RS, Alassaf I. The keyhole technique for arthroscopic tenodesis of the long head of the biceps tendon. In vivo prospective study with a radio-opaque marker. Orthop Traumatol Surg Res. 2015;101(1):31-34.
18. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
19. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc Rev. 2008;16(3):170-176.
20. Erickson BJ, Jain A, Abrams GD, et al. SLAP lesions: trends in treatment. Arthroscopy. 2016;32(6):976-981.
21. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.
22. Denard PJ, Ladermann A, Parsley BK, Burkhart SS. Arthroscopic biceps tenodesis compared with repair of isolated type II SLAP lesions in patients older than 35 years. Orthopedics. 2014;37(3):e292-e297.
23. Patterson BM, Creighton RA, Spang JT, Roberson JR, Kamath GV. Surgical trends in the treatment of superior labrum anterior and posterior lesions of the shoulder: analysis of data from the American Board of Orthopaedic Surgery certification examination database. Am J Sports Med. 2014;42(8):1904-1910.
24. Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.
25. Werner BC, Brockmeier SF, Gwathmey FW. Trends in long head biceps tenodesis. Am J Sports Med. 2015;43(3):570-578.
No survival benefit with adjuvant girentuximab in high-risk RCC
The monoclonal antibody girentuximab does not appear to have a clinical benefit in patients with high-risk clear cell renal cell carcinoma (ccRCC).
Adjuvant therapy with girentuximab failed to improve either disease-free or overall survival, compared with placebo, in a cohort of patients who had undergone full surgical resection, according to phase 3 results of the ARISER trial.
In a subset of patients with CAIX scores of 200 or greater, however, there was disease-free survival benefit although it did not reach significance, reported lead author Karim Chamie, MD, of the David Geffen School of Medicine at UCLA, and his colleagues (JAMA Oncol. 2017;3[7]:913-20).
The drug was well tolerated, with an excellent safety profile, and there were no reported drug-related serious adverse events.
“Our finding that girentuximab was more effective in the subgroup of patients younger than 65 years is consistent with these observations and, while requiring prospective confirmation, suggests that an insufficient activation of [antibody-dependent cellular cytotoxicity] could explain the failure of its efficacy,” wrote Dr. Chamie and his colleagues.
The authors also point out that “virtually all trials of adjuvant therapy in high-risk RCC have failed to show a treatment benefit,” and thus illustrates the difficulty in identifying successful adjuvant therapies.
“The success of future adjuvant trials will require use of inclusion criteria sufficiently broad to meet accrual goals while limiting inclusion to patients who are most likely to benefit from therapy,” they write.
Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein that is ubiquitously expressed in ccRCC. Phase 2 studies showed the agent to be safe and active in this setting, and served as the basis for conducting the current phase 3 ARISER trial (Adjuvant Rencarex Immunotherapy Phase 3 Trial to Study Efficacy in Nonmetastatic RCC).
The randomized, double-blind, placebo-controlled trial was conducted at 142 academic medical centers in 15 countries in North and South America and Europe and included a cohort of 864 patients who had undergone partial or radical nephrectomy for ccRCC and fell into one of the following high-risk groups: pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater.
The cohort was randomly assigned to either a single loading dose of girentuximab, 50 mg (week 1), followed by weekly intravenous infusions of girentuximab, 20 mg (weeks 2-24), or placebo, stratified by risk group and region.
The overall disease-free survival was comparable for the two groups: at 5 years it was 53.9% and 51.6% for the girentuximab and placebo groups, respectively, while the median disease-free survival was 71.4 months (interquartile range, 3 months to not reached) for patients who received girentuximab and was not reached for those receiving placebo (P = .74).
Median overall survival was not reached for either of the two groups, and there was no difference in overall survival between arms (hazard ratio, 0.99; 95% confidence interval, 0.74-1.32).
Adverse events were reported in 185 patients (21.6%), and were comparable between groups, and serious events occurred in 72 patients (8.4%), and were also comparable between the two arms.
The study was funded by Wilex, AG. Dr. Chamie receives research support from and serves as a consultant for UroGen Pharma, receives grant support from Phase One Foundation and Stop Cancer, and is a consultant for Cold Genesys and a scientific advisory board member of Altor. Several coauthors reported relationships with industry.
The monoclonal antibody girentuximab does not appear to have a clinical benefit in patients with high-risk clear cell renal cell carcinoma (ccRCC).
Adjuvant therapy with girentuximab failed to improve either disease-free or overall survival, compared with placebo, in a cohort of patients who had undergone full surgical resection, according to phase 3 results of the ARISER trial.
In a subset of patients with CAIX scores of 200 or greater, however, there was disease-free survival benefit although it did not reach significance, reported lead author Karim Chamie, MD, of the David Geffen School of Medicine at UCLA, and his colleagues (JAMA Oncol. 2017;3[7]:913-20).
The drug was well tolerated, with an excellent safety profile, and there were no reported drug-related serious adverse events.
“Our finding that girentuximab was more effective in the subgroup of patients younger than 65 years is consistent with these observations and, while requiring prospective confirmation, suggests that an insufficient activation of [antibody-dependent cellular cytotoxicity] could explain the failure of its efficacy,” wrote Dr. Chamie and his colleagues.
The authors also point out that “virtually all trials of adjuvant therapy in high-risk RCC have failed to show a treatment benefit,” and thus illustrates the difficulty in identifying successful adjuvant therapies.
“The success of future adjuvant trials will require use of inclusion criteria sufficiently broad to meet accrual goals while limiting inclusion to patients who are most likely to benefit from therapy,” they write.
Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein that is ubiquitously expressed in ccRCC. Phase 2 studies showed the agent to be safe and active in this setting, and served as the basis for conducting the current phase 3 ARISER trial (Adjuvant Rencarex Immunotherapy Phase 3 Trial to Study Efficacy in Nonmetastatic RCC).
The randomized, double-blind, placebo-controlled trial was conducted at 142 academic medical centers in 15 countries in North and South America and Europe and included a cohort of 864 patients who had undergone partial or radical nephrectomy for ccRCC and fell into one of the following high-risk groups: pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater.
The cohort was randomly assigned to either a single loading dose of girentuximab, 50 mg (week 1), followed by weekly intravenous infusions of girentuximab, 20 mg (weeks 2-24), or placebo, stratified by risk group and region.
The overall disease-free survival was comparable for the two groups: at 5 years it was 53.9% and 51.6% for the girentuximab and placebo groups, respectively, while the median disease-free survival was 71.4 months (interquartile range, 3 months to not reached) for patients who received girentuximab and was not reached for those receiving placebo (P = .74).
Median overall survival was not reached for either of the two groups, and there was no difference in overall survival between arms (hazard ratio, 0.99; 95% confidence interval, 0.74-1.32).
Adverse events were reported in 185 patients (21.6%), and were comparable between groups, and serious events occurred in 72 patients (8.4%), and were also comparable between the two arms.
The study was funded by Wilex, AG. Dr. Chamie receives research support from and serves as a consultant for UroGen Pharma, receives grant support from Phase One Foundation and Stop Cancer, and is a consultant for Cold Genesys and a scientific advisory board member of Altor. Several coauthors reported relationships with industry.
The monoclonal antibody girentuximab does not appear to have a clinical benefit in patients with high-risk clear cell renal cell carcinoma (ccRCC).
Adjuvant therapy with girentuximab failed to improve either disease-free or overall survival, compared with placebo, in a cohort of patients who had undergone full surgical resection, according to phase 3 results of the ARISER trial.
In a subset of patients with CAIX scores of 200 or greater, however, there was disease-free survival benefit although it did not reach significance, reported lead author Karim Chamie, MD, of the David Geffen School of Medicine at UCLA, and his colleagues (JAMA Oncol. 2017;3[7]:913-20).
The drug was well tolerated, with an excellent safety profile, and there were no reported drug-related serious adverse events.
“Our finding that girentuximab was more effective in the subgroup of patients younger than 65 years is consistent with these observations and, while requiring prospective confirmation, suggests that an insufficient activation of [antibody-dependent cellular cytotoxicity] could explain the failure of its efficacy,” wrote Dr. Chamie and his colleagues.
The authors also point out that “virtually all trials of adjuvant therapy in high-risk RCC have failed to show a treatment benefit,” and thus illustrates the difficulty in identifying successful adjuvant therapies.
“The success of future adjuvant trials will require use of inclusion criteria sufficiently broad to meet accrual goals while limiting inclusion to patients who are most likely to benefit from therapy,” they write.
Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein that is ubiquitously expressed in ccRCC. Phase 2 studies showed the agent to be safe and active in this setting, and served as the basis for conducting the current phase 3 ARISER trial (Adjuvant Rencarex Immunotherapy Phase 3 Trial to Study Efficacy in Nonmetastatic RCC).
The randomized, double-blind, placebo-controlled trial was conducted at 142 academic medical centers in 15 countries in North and South America and Europe and included a cohort of 864 patients who had undergone partial or radical nephrectomy for ccRCC and fell into one of the following high-risk groups: pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater.
The cohort was randomly assigned to either a single loading dose of girentuximab, 50 mg (week 1), followed by weekly intravenous infusions of girentuximab, 20 mg (weeks 2-24), or placebo, stratified by risk group and region.
The overall disease-free survival was comparable for the two groups: at 5 years it was 53.9% and 51.6% for the girentuximab and placebo groups, respectively, while the median disease-free survival was 71.4 months (interquartile range, 3 months to not reached) for patients who received girentuximab and was not reached for those receiving placebo (P = .74).
Median overall survival was not reached for either of the two groups, and there was no difference in overall survival between arms (hazard ratio, 0.99; 95% confidence interval, 0.74-1.32).
Adverse events were reported in 185 patients (21.6%), and were comparable between groups, and serious events occurred in 72 patients (8.4%), and were also comparable between the two arms.
The study was funded by Wilex, AG. Dr. Chamie receives research support from and serves as a consultant for UroGen Pharma, receives grant support from Phase One Foundation and Stop Cancer, and is a consultant for Cold Genesys and a scientific advisory board member of Altor. Several coauthors reported relationships with industry.
FROM JAMA ONCOLOGY
Key clinical point: Adjuvant girentuximab did not confer a survival benefit in patients with high-risk clear cell renal cell carcinoma.
Major finding: Five-year disease-free survival was 53.9% and 51.6% for the girentuximab and placebo groups, respectively.
Data source: A phase 3 placebo controlled multicenter clinical trial that included 864 patients with high-risk clear cell renal cell carcinoma.
Disclosures: The study was funded by Wilex, AG. Dr. Chamie receives research support from and serves as a consultant for UroGen Pharma, receives grant support from Phase One Foundation and Stop Cancer, and is a consultant for Cold Genesys and a scientific advisory board member of Altor. Several coauthors reported relationships with industry.
New tool predicts antimicrobial resistance in sepsis
Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.
Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).
The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).
Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.
Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.
Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.
The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.
Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.
The researchers had no financial conflicts to disclose.
Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.
Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).
The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).
Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.
Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.
Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.
The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.
Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.
The researchers had no financial conflicts to disclose.
Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.
Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).
The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).
Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.
Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.
Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.
The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.
Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.
The researchers had no financial conflicts to disclose.
FROM CLINICAL INFECTIOUS DISEASES
Key clinical point:
Major finding: The model found prevalence rates for resistance to piperacillin-tazobactam, cefepime, and meropenem of 28.6%, 21.8%, and 8.5%, respectively.
Data source: A review of 1,618 adults with sepsis.
Disclosures: The researchers had no financial conflicts to disclose.
VA Commits to Improving Health Care Provider Efficiency
The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”
In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:
- Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
- Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
- Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
- Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.
In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”
Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”
In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.
The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”
In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:
- Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
- Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
- Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
- Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.
In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”
Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”
In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.
The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”
In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:
- Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
- Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
- Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
- Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.
In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”
Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”
In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.
An Action Plan for Better COPD Care
A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.
The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.
An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:
- Empower patients, families, and caregivers to recognize and reduce the burden of COPD
- Equip health care professionals to provide comprehensive care to people with COPD
- Collect, analyze, report, and disseminate COPD data
- Increase and sustain COPD research
- Turn COPD recommendations into research and public health care actions
Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”
A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.
The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.
An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:
- Empower patients, families, and caregivers to recognize and reduce the burden of COPD
- Equip health care professionals to provide comprehensive care to people with COPD
- Collect, analyze, report, and disseminate COPD data
- Increase and sustain COPD research
- Turn COPD recommendations into research and public health care actions
Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”
A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.
The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.
An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:
- Empower patients, families, and caregivers to recognize and reduce the burden of COPD
- Equip health care professionals to provide comprehensive care to people with COPD
- Collect, analyze, report, and disseminate COPD data
- Increase and sustain COPD research
- Turn COPD recommendations into research and public health care actions
Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”
CAR T-cell therapy ‘highly effective’ in high-risk CLL
A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.
The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.
Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.
Researchers reported these results in The Journal of Clinical Oncology.
The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.
The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.
“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”
Treatment and safety
All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.
Patients received JCAR014 at 1 of 3 dose levels—2 x 105, 2 x 106, or 2 x 107 CAR T cells/kg.
Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.
Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).
Initial response
The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).
One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.
One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.
Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.
The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.
Second dose
Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).
Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).
Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.
Survival
Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.
The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).
The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).
The researchers also found that IGH sequencing revealed patients with durable PFS.
The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25). 
A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.
The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.
Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.
Researchers reported these results in The Journal of Clinical Oncology.
The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.
The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.
“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”
Treatment and safety
All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.
Patients received JCAR014 at 1 of 3 dose levels—2 x 105, 2 x 106, or 2 x 107 CAR T cells/kg.
Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.
Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).
Initial response
The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).
One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.
One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.
Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.
The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.
Second dose
Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).
Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).
Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.
Survival
Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.
The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).
The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).
The researchers also found that IGH sequencing revealed patients with durable PFS.
The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25).
A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.
The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.
Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.
Researchers reported these results in The Journal of Clinical Oncology.
The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.
The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.
“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”
Treatment and safety
All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.
Patients received JCAR014 at 1 of 3 dose levels—2 x 105, 2 x 106, or 2 x 107 CAR T cells/kg.
Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.
Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).
Initial response
The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).
One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.
One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.
Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.
The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.
Second dose
Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).
Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).
Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.
Survival
Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.
The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).
The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).
The researchers also found that IGH sequencing revealed patients with durable PFS.
The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25).