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How the ADA shapes health care
Question: After many years of diabetes, a 60-year-old office worker develops nephropathy followed by end-stage renal disease, and now requires dialysis. He has opted for peritoneal dialysis rather than hemodialysis, so that he does not have to be away from the workplace for treatment. His diabetes is insulin requiring, and he has occasional hypoglycemic reactions. Although he qualifies for Social Security disability benefits, he prefers to continue working full time. The employer is considering terminating him.
Which of the following is best?
A. The Americans with Disabilities Act prohibits job discrimination against patients with disabilities, so long as they are otherwise qualified for every aspect of the job.
B. Renal insufficiency and diabetes are considered disabilities under the ADA.
C. The employer is obligated to provide full accommodation to enable this employee to continue working.
D. If the accommodations needed for a disabled person are unreasonable, or prove too disruptive or expensive, then the employer is not obligated to provide them.
E. This patient should simply retire and enjoy his SS disability benefits.
Answer: D. Enacted in 1990, the Americans with Disabilities Act seeks to provide clear, strong, consistent, and enforceable standards for ending discrimination against individuals with disabilities.1 The main thrust of the ADA, Title I, is to protect otherwise qualified workers with permanent disabilities from losing their jobs or seeking one, so long as they are qualified to perform the essential (not necessarily all) functions of the job.
In addition, the law prohibits discrimination against people with disabilities from accessing public accommodations (Title III), which include doctors’ offices and health care facilities, as well as restaurants, retail stores, etc. Other areas under the purview of the omnibus ADA include transportation, communications, and access to state and local government programs and services.
The Equal Employment Opportunity Commission (EEOC) enforces Title I of the ADA, the section that deals with job discrimination. Its compliance manual sets out guidelines for determining whether an individual in fact has a disability.
The word “disability” has three components, and the term is not synonymous with “impairment.” However, a disability begins with having an impairment, defined as a physiological disorder affecting one or more of a number of body systems or a mental or psychological disorder.
An example given by the EEOC: If a person cannot find a job because that person has the equivalent of a second-grade education and therefore cannot read, that person does not have an impairment for purposes of the ADA. If, however, that person cannot read because of severe dyslexia, that person has an impairment. Likewise, being overweight is not considered an impairment (unless due to an underlying physical condition, e.g., hypothyroidism), although extreme obesity in excess of 100% ideal body weight is.
Having determined that an impairment exists, the next step in the analysis is to ascertain if the impairment limits one or more “major life activities.” These have classically included activities such as caring for oneself, performing manual tasks, walking, seeing, hearing, speaking, and breathing.
Third, the limitation must be substantial, meaning sufficiently severe, compared with what an average person is capable of doing. According to the EEOC, a mild type 2 diabetes patient on diet treatment alone and no other restriction has an impairment; but the impairment does not substantially limit any of his major life activities. On the other hand, some impairments are so severe that there is no doubt they substantially limit major life activities, e.g., insulin-dependent diabetes, legal blindness, deafness, manic-depressive syndrome, alcoholism, and HIV infection.
There is litigation aplenty over these issues.
In its seminal 1988 case, the U.S. Supreme Court provided the analytical steps listed above in arriving at its holding that, under the ADA, asymptomatic HIV infection is a disability.2 The case involved a dentist who was sued when he declined to treat an HIV-positive female patient in the office, offering instead to treat her in a hospital without any additional charge. A dental office, like a doctor’s office, is recognized as a place of public accommodations, and therefore falls under the protection of Title III of the ADA.
The court first considered whether HIV infection was a physical impairment. Second, it identified the major life activity upon which the plaintiff relied (reproduction and childbearing) and determined whether it constituted a major life activity under the ADA. Third, it tied the two statutory phrases together, and asked whether the impairment substantially limited these major life activities.
The court held that, in light of the immediacy with which the HIV virus begins to damage the infected person’s white blood cells and the severity of the disease, it is an impairment from the moment of infection, even if the patient was asymptomatic. It also ruled that the HIV infection substantially limited her ability to reproduce in two independent ways. First, a woman infected with HIV who tries to conceive a child imposes on the man a significant risk of becoming infected, and second, an infected woman risks infecting her child during gestation and childbirth, i.e., perinatal transmission.
In 2004, a case reached the U.S. Third Circuit Court of Appeals regarding Cathy Fiscus, an employee at a Walmart Sam’s Club warehouse store in Pittsburgh, who faced being terminated after 12 years at her job. A lower U.S. district court had ruled in favor of the company, agreeing with Walmart that the woman’s end-stage renal disease had not left her significantly limited in a major life activity. Ms. Fiscus sought a reasonable accommodation from her employer during the period of her peritoneal dialysis, which required her to self administer the 45-minute dialysis process at the workplace. Walmart initially agreed, but later declined. The appeals court overturned the lower court’s ruling, writing, “A physical impairment that limits an individual’s ability to cleanse and eliminate body waste does impair a major life activity.”3
Not all conditions are covered by the ADA’s definition of disability. The list includes temporary physical or mental impairments, current illegal drug use, predisposition to illness, personality traits, advanced age, and pregnancy, to name a few.
To avoid running afoul of the ADA, an employer is required to make “reasonable accommodations” for the disabled employee. This refers to practices that allow a disabled person to perform the essential functions of the job.
Examples of reasonable accommodations include making existing facilities readily accessible to and usable by individuals with disabilities, restructuring jobs, modifying work schedules, and providing qualified readers or interpreters.
A “qualified individual with a disability” is an individual with a disability who, “with or without reasonable accommodation,” can perform the essential functions of the employment position in question. A person is not a qualified individual with a disability, however, if he or she cannot satisfy the basic attendance requirements of a position.
Employers are not required to offer any and all accommodations, such as those that are disruptive to the business, overly burdensome, or prohibitively expensive. Providing a clean and private area in the workplace for self-administered peritoneal dialysis fluid exchange would likely qualify as a reasonable accommodation that should be offered, absent some compelling reason not to.
The protection given by the ADA may be suspended if the condition poses a direct threat, defined as “a significant risk to the health or safety of others that cannot be eliminated by a modification of policies, practices, or procedures, or by the provision of auxiliary aids or services.”4 The U.S. Supreme Court has noted that this should be assessed by the objective reasonableness of the views of health care professionals.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Americans with Disabilities Act of 1990 (ADA), 104 Stat. 327, 42 U. S. C. § 12101 et seq.
2. Bragdon v. Abbott et al. 524 U.S. 624 (1998).
3. Cathy A. Fiscus v. Wal-Mart Stores Inc., 385 F.3d 378 (3d Cir. 2004).
4. 42 U. S. C. § 12182(b)(3).
5. Available at www.kidney.org/atoz/content/employersguide.
Question: After many years of diabetes, a 60-year-old office worker develops nephropathy followed by end-stage renal disease, and now requires dialysis. He has opted for peritoneal dialysis rather than hemodialysis, so that he does not have to be away from the workplace for treatment. His diabetes is insulin requiring, and he has occasional hypoglycemic reactions. Although he qualifies for Social Security disability benefits, he prefers to continue working full time. The employer is considering terminating him.
Which of the following is best?
A. The Americans with Disabilities Act prohibits job discrimination against patients with disabilities, so long as they are otherwise qualified for every aspect of the job.
B. Renal insufficiency and diabetes are considered disabilities under the ADA.
C. The employer is obligated to provide full accommodation to enable this employee to continue working.
D. If the accommodations needed for a disabled person are unreasonable, or prove too disruptive or expensive, then the employer is not obligated to provide them.
E. This patient should simply retire and enjoy his SS disability benefits.
Answer: D. Enacted in 1990, the Americans with Disabilities Act seeks to provide clear, strong, consistent, and enforceable standards for ending discrimination against individuals with disabilities.1 The main thrust of the ADA, Title I, is to protect otherwise qualified workers with permanent disabilities from losing their jobs or seeking one, so long as they are qualified to perform the essential (not necessarily all) functions of the job.
In addition, the law prohibits discrimination against people with disabilities from accessing public accommodations (Title III), which include doctors’ offices and health care facilities, as well as restaurants, retail stores, etc. Other areas under the purview of the omnibus ADA include transportation, communications, and access to state and local government programs and services.
The Equal Employment Opportunity Commission (EEOC) enforces Title I of the ADA, the section that deals with job discrimination. Its compliance manual sets out guidelines for determining whether an individual in fact has a disability.
The word “disability” has three components, and the term is not synonymous with “impairment.” However, a disability begins with having an impairment, defined as a physiological disorder affecting one or more of a number of body systems or a mental or psychological disorder.
An example given by the EEOC: If a person cannot find a job because that person has the equivalent of a second-grade education and therefore cannot read, that person does not have an impairment for purposes of the ADA. If, however, that person cannot read because of severe dyslexia, that person has an impairment. Likewise, being overweight is not considered an impairment (unless due to an underlying physical condition, e.g., hypothyroidism), although extreme obesity in excess of 100% ideal body weight is.
Having determined that an impairment exists, the next step in the analysis is to ascertain if the impairment limits one or more “major life activities.” These have classically included activities such as caring for oneself, performing manual tasks, walking, seeing, hearing, speaking, and breathing.
Third, the limitation must be substantial, meaning sufficiently severe, compared with what an average person is capable of doing. According to the EEOC, a mild type 2 diabetes patient on diet treatment alone and no other restriction has an impairment; but the impairment does not substantially limit any of his major life activities. On the other hand, some impairments are so severe that there is no doubt they substantially limit major life activities, e.g., insulin-dependent diabetes, legal blindness, deafness, manic-depressive syndrome, alcoholism, and HIV infection.
There is litigation aplenty over these issues.
In its seminal 1988 case, the U.S. Supreme Court provided the analytical steps listed above in arriving at its holding that, under the ADA, asymptomatic HIV infection is a disability.2 The case involved a dentist who was sued when he declined to treat an HIV-positive female patient in the office, offering instead to treat her in a hospital without any additional charge. A dental office, like a doctor’s office, is recognized as a place of public accommodations, and therefore falls under the protection of Title III of the ADA.
The court first considered whether HIV infection was a physical impairment. Second, it identified the major life activity upon which the plaintiff relied (reproduction and childbearing) and determined whether it constituted a major life activity under the ADA. Third, it tied the two statutory phrases together, and asked whether the impairment substantially limited these major life activities.
The court held that, in light of the immediacy with which the HIV virus begins to damage the infected person’s white blood cells and the severity of the disease, it is an impairment from the moment of infection, even if the patient was asymptomatic. It also ruled that the HIV infection substantially limited her ability to reproduce in two independent ways. First, a woman infected with HIV who tries to conceive a child imposes on the man a significant risk of becoming infected, and second, an infected woman risks infecting her child during gestation and childbirth, i.e., perinatal transmission.
In 2004, a case reached the U.S. Third Circuit Court of Appeals regarding Cathy Fiscus, an employee at a Walmart Sam’s Club warehouse store in Pittsburgh, who faced being terminated after 12 years at her job. A lower U.S. district court had ruled in favor of the company, agreeing with Walmart that the woman’s end-stage renal disease had not left her significantly limited in a major life activity. Ms. Fiscus sought a reasonable accommodation from her employer during the period of her peritoneal dialysis, which required her to self administer the 45-minute dialysis process at the workplace. Walmart initially agreed, but later declined. The appeals court overturned the lower court’s ruling, writing, “A physical impairment that limits an individual’s ability to cleanse and eliminate body waste does impair a major life activity.”3
Not all conditions are covered by the ADA’s definition of disability. The list includes temporary physical or mental impairments, current illegal drug use, predisposition to illness, personality traits, advanced age, and pregnancy, to name a few.
To avoid running afoul of the ADA, an employer is required to make “reasonable accommodations” for the disabled employee. This refers to practices that allow a disabled person to perform the essential functions of the job.
Examples of reasonable accommodations include making existing facilities readily accessible to and usable by individuals with disabilities, restructuring jobs, modifying work schedules, and providing qualified readers or interpreters.
A “qualified individual with a disability” is an individual with a disability who, “with or without reasonable accommodation,” can perform the essential functions of the employment position in question. A person is not a qualified individual with a disability, however, if he or she cannot satisfy the basic attendance requirements of a position.
Employers are not required to offer any and all accommodations, such as those that are disruptive to the business, overly burdensome, or prohibitively expensive. Providing a clean and private area in the workplace for self-administered peritoneal dialysis fluid exchange would likely qualify as a reasonable accommodation that should be offered, absent some compelling reason not to.
The protection given by the ADA may be suspended if the condition poses a direct threat, defined as “a significant risk to the health or safety of others that cannot be eliminated by a modification of policies, practices, or procedures, or by the provision of auxiliary aids or services.”4 The U.S. Supreme Court has noted that this should be assessed by the objective reasonableness of the views of health care professionals.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Americans with Disabilities Act of 1990 (ADA), 104 Stat. 327, 42 U. S. C. § 12101 et seq.
2. Bragdon v. Abbott et al. 524 U.S. 624 (1998).
3. Cathy A. Fiscus v. Wal-Mart Stores Inc., 385 F.3d 378 (3d Cir. 2004).
4. 42 U. S. C. § 12182(b)(3).
5. Available at www.kidney.org/atoz/content/employersguide.
Question: After many years of diabetes, a 60-year-old office worker develops nephropathy followed by end-stage renal disease, and now requires dialysis. He has opted for peritoneal dialysis rather than hemodialysis, so that he does not have to be away from the workplace for treatment. His diabetes is insulin requiring, and he has occasional hypoglycemic reactions. Although he qualifies for Social Security disability benefits, he prefers to continue working full time. The employer is considering terminating him.
Which of the following is best?
A. The Americans with Disabilities Act prohibits job discrimination against patients with disabilities, so long as they are otherwise qualified for every aspect of the job.
B. Renal insufficiency and diabetes are considered disabilities under the ADA.
C. The employer is obligated to provide full accommodation to enable this employee to continue working.
D. If the accommodations needed for a disabled person are unreasonable, or prove too disruptive or expensive, then the employer is not obligated to provide them.
E. This patient should simply retire and enjoy his SS disability benefits.
Answer: D. Enacted in 1990, the Americans with Disabilities Act seeks to provide clear, strong, consistent, and enforceable standards for ending discrimination against individuals with disabilities.1 The main thrust of the ADA, Title I, is to protect otherwise qualified workers with permanent disabilities from losing their jobs or seeking one, so long as they are qualified to perform the essential (not necessarily all) functions of the job.
In addition, the law prohibits discrimination against people with disabilities from accessing public accommodations (Title III), which include doctors’ offices and health care facilities, as well as restaurants, retail stores, etc. Other areas under the purview of the omnibus ADA include transportation, communications, and access to state and local government programs and services.
The Equal Employment Opportunity Commission (EEOC) enforces Title I of the ADA, the section that deals with job discrimination. Its compliance manual sets out guidelines for determining whether an individual in fact has a disability.
The word “disability” has three components, and the term is not synonymous with “impairment.” However, a disability begins with having an impairment, defined as a physiological disorder affecting one or more of a number of body systems or a mental or psychological disorder.
An example given by the EEOC: If a person cannot find a job because that person has the equivalent of a second-grade education and therefore cannot read, that person does not have an impairment for purposes of the ADA. If, however, that person cannot read because of severe dyslexia, that person has an impairment. Likewise, being overweight is not considered an impairment (unless due to an underlying physical condition, e.g., hypothyroidism), although extreme obesity in excess of 100% ideal body weight is.
Having determined that an impairment exists, the next step in the analysis is to ascertain if the impairment limits one or more “major life activities.” These have classically included activities such as caring for oneself, performing manual tasks, walking, seeing, hearing, speaking, and breathing.
Third, the limitation must be substantial, meaning sufficiently severe, compared with what an average person is capable of doing. According to the EEOC, a mild type 2 diabetes patient on diet treatment alone and no other restriction has an impairment; but the impairment does not substantially limit any of his major life activities. On the other hand, some impairments are so severe that there is no doubt they substantially limit major life activities, e.g., insulin-dependent diabetes, legal blindness, deafness, manic-depressive syndrome, alcoholism, and HIV infection.
There is litigation aplenty over these issues.
In its seminal 1988 case, the U.S. Supreme Court provided the analytical steps listed above in arriving at its holding that, under the ADA, asymptomatic HIV infection is a disability.2 The case involved a dentist who was sued when he declined to treat an HIV-positive female patient in the office, offering instead to treat her in a hospital without any additional charge. A dental office, like a doctor’s office, is recognized as a place of public accommodations, and therefore falls under the protection of Title III of the ADA.
The court first considered whether HIV infection was a physical impairment. Second, it identified the major life activity upon which the plaintiff relied (reproduction and childbearing) and determined whether it constituted a major life activity under the ADA. Third, it tied the two statutory phrases together, and asked whether the impairment substantially limited these major life activities.
The court held that, in light of the immediacy with which the HIV virus begins to damage the infected person’s white blood cells and the severity of the disease, it is an impairment from the moment of infection, even if the patient was asymptomatic. It also ruled that the HIV infection substantially limited her ability to reproduce in two independent ways. First, a woman infected with HIV who tries to conceive a child imposes on the man a significant risk of becoming infected, and second, an infected woman risks infecting her child during gestation and childbirth, i.e., perinatal transmission.
In 2004, a case reached the U.S. Third Circuit Court of Appeals regarding Cathy Fiscus, an employee at a Walmart Sam’s Club warehouse store in Pittsburgh, who faced being terminated after 12 years at her job. A lower U.S. district court had ruled in favor of the company, agreeing with Walmart that the woman’s end-stage renal disease had not left her significantly limited in a major life activity. Ms. Fiscus sought a reasonable accommodation from her employer during the period of her peritoneal dialysis, which required her to self administer the 45-minute dialysis process at the workplace. Walmart initially agreed, but later declined. The appeals court overturned the lower court’s ruling, writing, “A physical impairment that limits an individual’s ability to cleanse and eliminate body waste does impair a major life activity.”3
Not all conditions are covered by the ADA’s definition of disability. The list includes temporary physical or mental impairments, current illegal drug use, predisposition to illness, personality traits, advanced age, and pregnancy, to name a few.
To avoid running afoul of the ADA, an employer is required to make “reasonable accommodations” for the disabled employee. This refers to practices that allow a disabled person to perform the essential functions of the job.
Examples of reasonable accommodations include making existing facilities readily accessible to and usable by individuals with disabilities, restructuring jobs, modifying work schedules, and providing qualified readers or interpreters.
A “qualified individual with a disability” is an individual with a disability who, “with or without reasonable accommodation,” can perform the essential functions of the employment position in question. A person is not a qualified individual with a disability, however, if he or she cannot satisfy the basic attendance requirements of a position.
Employers are not required to offer any and all accommodations, such as those that are disruptive to the business, overly burdensome, or prohibitively expensive. Providing a clean and private area in the workplace for self-administered peritoneal dialysis fluid exchange would likely qualify as a reasonable accommodation that should be offered, absent some compelling reason not to.
The protection given by the ADA may be suspended if the condition poses a direct threat, defined as “a significant risk to the health or safety of others that cannot be eliminated by a modification of policies, practices, or procedures, or by the provision of auxiliary aids or services.”4 The U.S. Supreme Court has noted that this should be assessed by the objective reasonableness of the views of health care professionals.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Americans with Disabilities Act of 1990 (ADA), 104 Stat. 327, 42 U. S. C. § 12101 et seq.
2. Bragdon v. Abbott et al. 524 U.S. 624 (1998).
3. Cathy A. Fiscus v. Wal-Mart Stores Inc., 385 F.3d 378 (3d Cir. 2004).
4. 42 U. S. C. § 12182(b)(3).
5. Available at www.kidney.org/atoz/content/employersguide.
VAM Registration Now Open
Registration and housing for the 2018 Vascular Annual Meeting are now open. Register today for VAM, June 20 to 23 in Boston, including looking over housing options. Following a full day of postgraduate courses, VESS abstracts, workshops and international programming on Wednesday, June 20, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Registration and housing for the 2018 Vascular Annual Meeting are now open. Register today for VAM, June 20 to 23 in Boston, including looking over housing options. Following a full day of postgraduate courses, VESS abstracts, workshops and international programming on Wednesday, June 20, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Registration and housing for the 2018 Vascular Annual Meeting are now open. Register today for VAM, June 20 to 23 in Boston, including looking over housing options. Following a full day of postgraduate courses, VESS abstracts, workshops and international programming on Wednesday, June 20, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Catch the Innovation Spirit: Register for VRIC
Register today for this year’s Vascular Research Initiatives Conference, May 9, in San Francisco. The theme “Road to Innovation, Invention and Enterprise,” is reflected in the Translational Panel presentation, "Road to Entrepreneurship." Also part of VRIC are four abstract sessions, on stem cells and regeneration, PAD, vascular endothelium and thrombosis and vascular inflammation and injury.
Register today for this year’s Vascular Research Initiatives Conference, May 9, in San Francisco. The theme “Road to Innovation, Invention and Enterprise,” is reflected in the Translational Panel presentation, "Road to Entrepreneurship." Also part of VRIC are four abstract sessions, on stem cells and regeneration, PAD, vascular endothelium and thrombosis and vascular inflammation and injury.
Register today for this year’s Vascular Research Initiatives Conference, May 9, in San Francisco. The theme “Road to Innovation, Invention and Enterprise,” is reflected in the Translational Panel presentation, "Road to Entrepreneurship." Also part of VRIC are four abstract sessions, on stem cells and regeneration, PAD, vascular endothelium and thrombosis and vascular inflammation and injury.
ABS announces Continuous Certification Program
The American Board of Surgery has announced the details of its new Continuous Certification Program, shaped by surgeon feedback and designed to provide greater value, flexibility and convenience in maintaining ABS board certification. Instead of taking one recertification exam every 10 years, surgeons will use the new program to demonstrate their surgical knowledge on a continual basis. General surgeons will follow the new assessment this year; members of other ABS specialties will do so over the next few years.
The American Board of Surgery has announced the details of its new Continuous Certification Program, shaped by surgeon feedback and designed to provide greater value, flexibility and convenience in maintaining ABS board certification. Instead of taking one recertification exam every 10 years, surgeons will use the new program to demonstrate their surgical knowledge on a continual basis. General surgeons will follow the new assessment this year; members of other ABS specialties will do so over the next few years.
The American Board of Surgery has announced the details of its new Continuous Certification Program, shaped by surgeon feedback and designed to provide greater value, flexibility and convenience in maintaining ABS board certification. Instead of taking one recertification exam every 10 years, surgeons will use the new program to demonstrate their surgical knowledge on a continual basis. General surgeons will follow the new assessment this year; members of other ABS specialties will do so over the next few years.
Women, Leadership Training Grant Deadline Extended to March 21
The application for the SVS Women’s Leadership Training Grant has been extended a week, to March 21. This grant seeks to identify female surgeons who want to sharpen their leadership skills. It provides a $5,000 award to help defray costs for travel, hotel accommodations and registration expenses to attend relevant courses and/or other leadership training opportunities and activities.
The application for the SVS Women’s Leadership Training Grant has been extended a week, to March 21. This grant seeks to identify female surgeons who want to sharpen their leadership skills. It provides a $5,000 award to help defray costs for travel, hotel accommodations and registration expenses to attend relevant courses and/or other leadership training opportunities and activities.
The application for the SVS Women’s Leadership Training Grant has been extended a week, to March 21. This grant seeks to identify female surgeons who want to sharpen their leadership skills. It provides a $5,000 award to help defray costs for travel, hotel accommodations and registration expenses to attend relevant courses and/or other leadership training opportunities and activities.
Children, adolescents with TBI at risk of secondary ADHD
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
Key clinical point: Children and adolescents with traumatic brain injury (TBI) should continue to be monitored for possible attention problems many years after the injury.
Major finding: In assessments taken up to 6.8 years after injury, severe TBI was associated with secondary ADHD, compared with a control group (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26).
Study details: Analysis of a prospective concurrent cohort study including 187 children aged 3 to 7 years who were hospitalized for TBI or orthopedic injury.
Disclosures: The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services. The authors reported conflict of interest disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
Source: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi:10.1001/jamapediatrics.2017.5746.
Pre-screening could help identify NAFLD biopsy candidates
PHILADELPHIA – When evaluating patients with established non-alcoholic fatty liver disease (NAFLD), using pre-screening criteria may help identify the subset of patients who should be subjected to liver biopsy, according to Vinod K. Rustgi, MD.
The recently described pre-screening criteria include a set of patient and disease characteristics that identify who might be at highest risk for non-alcoholic steatohepatitis (NASH) and fibrosis, said Dr. Rustgi, chief of hepatology at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.
“Eighty-five percent of the patients who fall into this category will actually have fibrosis on liver biopsy. So it’s a good way to screen out who you want to actually biopsy,” Dr. Rustgi said at the meeting, jointly provided by Rutgers and Global Academy for Medical Education.
Liver biopsy needs to be considered in patients with NAFLD who are at increased risk of having advanced fibrosis, according to the latest practice guidance on diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57).
While it’s the most accurate means to diagnose and stage severity of NASH, biopsy is invasive, costly, and associated with potential complications, according to a recent Hepatology review article (2017 Dec 9. doi: 10.1002/hep.29721).
Criteria to pinpoint patients at highest risk for NASH and fibrosis could be useful for streamlining clinical trial enrollment and limiting screening failures, according to authors who recently described the pre-screening criteria in the Journal of Hepatology (2018 Feb. doi: 10.1016/j.jhep.2017.10.015).
, or who have a vibration controlled transient elastography (VCTE, FibroScan) score of kPa greater than 8.5, or an AST/ALT ratio greater than 1, among several other criteria described in the article.
“The patients who have a low likelihood of NASH and fibrosis are those who are under the age of 40, who may not be diabetic, who have a elastography score of kPa less than 7, or an AST less than 20,” Dr. Rustgi said of the pre-screening criteria.
In his presentation, Dr. Rustgi provided other notes on when to biopsy as described in the January 2018 practice guidance from Hepatology.
In particular, the guidance states that presence of metabolic syndrome, NAFLD fibrosis score or Fibrosis 4 Score, or liver stiffness measured by VCTE or magnetic resonance elastography might be used to help identify patients at risk for steatohepatitis or advanced fibrosis.
Liver biopsy also should be considered in NAFLD when competing etiologies cannot be excluded except by a liver biopsy, according to the recent guidance.
Dr. Rustgi reported disclosures related to AbbVie, Genfit, and Gilead Sciences.
Global Academy for Medical Education and this news organization are owned by the same company.
PHILADELPHIA – When evaluating patients with established non-alcoholic fatty liver disease (NAFLD), using pre-screening criteria may help identify the subset of patients who should be subjected to liver biopsy, according to Vinod K. Rustgi, MD.
The recently described pre-screening criteria include a set of patient and disease characteristics that identify who might be at highest risk for non-alcoholic steatohepatitis (NASH) and fibrosis, said Dr. Rustgi, chief of hepatology at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.
“Eighty-five percent of the patients who fall into this category will actually have fibrosis on liver biopsy. So it’s a good way to screen out who you want to actually biopsy,” Dr. Rustgi said at the meeting, jointly provided by Rutgers and Global Academy for Medical Education.
Liver biopsy needs to be considered in patients with NAFLD who are at increased risk of having advanced fibrosis, according to the latest practice guidance on diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57).
While it’s the most accurate means to diagnose and stage severity of NASH, biopsy is invasive, costly, and associated with potential complications, according to a recent Hepatology review article (2017 Dec 9. doi: 10.1002/hep.29721).
Criteria to pinpoint patients at highest risk for NASH and fibrosis could be useful for streamlining clinical trial enrollment and limiting screening failures, according to authors who recently described the pre-screening criteria in the Journal of Hepatology (2018 Feb. doi: 10.1016/j.jhep.2017.10.015).
, or who have a vibration controlled transient elastography (VCTE, FibroScan) score of kPa greater than 8.5, or an AST/ALT ratio greater than 1, among several other criteria described in the article.
“The patients who have a low likelihood of NASH and fibrosis are those who are under the age of 40, who may not be diabetic, who have a elastography score of kPa less than 7, or an AST less than 20,” Dr. Rustgi said of the pre-screening criteria.
In his presentation, Dr. Rustgi provided other notes on when to biopsy as described in the January 2018 practice guidance from Hepatology.
In particular, the guidance states that presence of metabolic syndrome, NAFLD fibrosis score or Fibrosis 4 Score, or liver stiffness measured by VCTE or magnetic resonance elastography might be used to help identify patients at risk for steatohepatitis or advanced fibrosis.
Liver biopsy also should be considered in NAFLD when competing etiologies cannot be excluded except by a liver biopsy, according to the recent guidance.
Dr. Rustgi reported disclosures related to AbbVie, Genfit, and Gilead Sciences.
Global Academy for Medical Education and this news organization are owned by the same company.
PHILADELPHIA – When evaluating patients with established non-alcoholic fatty liver disease (NAFLD), using pre-screening criteria may help identify the subset of patients who should be subjected to liver biopsy, according to Vinod K. Rustgi, MD.
The recently described pre-screening criteria include a set of patient and disease characteristics that identify who might be at highest risk for non-alcoholic steatohepatitis (NASH) and fibrosis, said Dr. Rustgi, chief of hepatology at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.
“Eighty-five percent of the patients who fall into this category will actually have fibrosis on liver biopsy. So it’s a good way to screen out who you want to actually biopsy,” Dr. Rustgi said at the meeting, jointly provided by Rutgers and Global Academy for Medical Education.
Liver biopsy needs to be considered in patients with NAFLD who are at increased risk of having advanced fibrosis, according to the latest practice guidance on diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57).
While it’s the most accurate means to diagnose and stage severity of NASH, biopsy is invasive, costly, and associated with potential complications, according to a recent Hepatology review article (2017 Dec 9. doi: 10.1002/hep.29721).
Criteria to pinpoint patients at highest risk for NASH and fibrosis could be useful for streamlining clinical trial enrollment and limiting screening failures, according to authors who recently described the pre-screening criteria in the Journal of Hepatology (2018 Feb. doi: 10.1016/j.jhep.2017.10.015).
, or who have a vibration controlled transient elastography (VCTE, FibroScan) score of kPa greater than 8.5, or an AST/ALT ratio greater than 1, among several other criteria described in the article.
“The patients who have a low likelihood of NASH and fibrosis are those who are under the age of 40, who may not be diabetic, who have a elastography score of kPa less than 7, or an AST less than 20,” Dr. Rustgi said of the pre-screening criteria.
In his presentation, Dr. Rustgi provided other notes on when to biopsy as described in the January 2018 practice guidance from Hepatology.
In particular, the guidance states that presence of metabolic syndrome, NAFLD fibrosis score or Fibrosis 4 Score, or liver stiffness measured by VCTE or magnetic resonance elastography might be used to help identify patients at risk for steatohepatitis or advanced fibrosis.
Liver biopsy also should be considered in NAFLD when competing etiologies cannot be excluded except by a liver biopsy, according to the recent guidance.
Dr. Rustgi reported disclosures related to AbbVie, Genfit, and Gilead Sciences.
Global Academy for Medical Education and this news organization are owned by the same company.
REPORTING FROM DIGESTIVE DISEASES: NEW ADVANCES
MDedge Daily News: Three daily meals best in type 2 diabetes
Three regular meals a day are best for type 2 diabetes, surgery is more successful for adrenal cortical carcinoma, how thyroid-stimulating hormone affects infertility, and new practice guidelines on testosterone therapy make their debut.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Three regular meals a day are best for type 2 diabetes, surgery is more successful for adrenal cortical carcinoma, how thyroid-stimulating hormone affects infertility, and new practice guidelines on testosterone therapy make their debut.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Three regular meals a day are best for type 2 diabetes, surgery is more successful for adrenal cortical carcinoma, how thyroid-stimulating hormone affects infertility, and new practice guidelines on testosterone therapy make their debut.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Stroke Patients May Have a Wider Window of Treatment Opportunity
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”
Metabolic changes in T cells may limit CAR potential in kids
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”