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Motor function restored in three men after complete paralysis from spinal cord injury
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Is there a cure for aging?
Heart disease. Cancer. Diabetes. Dementia.
Researchers spend billions of dollars every year trying to eradicate these medical scourges.
Yet even if we discover cures to these and all other chronic conditions, it won’t change our ultimate prognosis: death.
“That’s because you haven’t stopped aging,” says Jay Olshansky, PhD, a professor of epidemiology and biostatistics at the University of Illinois at Chicago School of Public Health.
But what if we could?
Some scientists think so. Fueled in part by a billion dollars of investor money, they are attempting to reverse-engineer your molecular biological clock. Their goal? To eliminate not merely diseases that kill people, but to prevent death itself.
Hacking the code for immortality
Aubrey de Grey, PhD, a biomedical gerontologist, has drawn wide attention for his belief that the first person who will live to be 1,000 years old is already among us.
He believes there’s no cap on how long we can live, depending on what medicines we develop in the future.
“The whole idea is that there would not be a limit on how long we can keep people healthy,” Dr. de Grey says. He’s the chief science officer and co-founder of the SENS Research Foundation, which funds research on how to put the brakes on aging.
Dr. De Grey’s view, in theory, isn’t so far-fetched.
Scientists have studied the immortal jellyfish, Turritopsis dohrnii. It’s the only animal that can cheat death by reverting from adulthood back to its polyp stage when threatened with danger or starvation.
Other clues to possible eternal life also may exist underwater. Certain marine clams can live more than 500 years. And lobsters stock a seemingly limitless supply of a youthful enzyme that has some scientists wondering if the crustacean, under the best conditions, just might live forever.
Among humans, researchers have been studying “super-agers” – people who not only live exceptionally long, but also do so without many of the chronic diseases that plague their peers. That’s even though they share some of the same bad habits as everyone else.
“They are making it past the age of 80 with their minds completely intact. That’s what’s so unusual,” Dr. Olshansky says. The rest of their bodies are doing better than those of average 80-year-olds, too.
People who reached ages 95 to 112 got cancer, heart disease, diabetes, osteoporosis, and stroke up to 24 years later than those with average lifespans, data show. Figuring out why might pave the way for targeted gene therapy to mimic the DNA of these nonagenarians and centenarians.
“There’s likely to be secrets contained within their genome that are eventually discovered that will help us develop therapeutic interventions to mimic the effects of decelerated aging,” Dr. Olshansky says.
Treating aging this way may offer a bigger payoff than targeting individual diseases. That’s because even if you manage to dodge any illnesses, there’s ultimately no escaping old age.
“Longevity is a side effect of health,” Dr. de Grey says. “If we can keep people healthy, then their likelihood of dying is reduced.”
Aging as a preventable condition
In 2015, Michael Cantor was prescribed metformin for prediabetes. Once that was under control, his doctor said Mr. Cantor could quit the drug. But Mr. Cantor had heard about studies testing it as an anti-aging drug. The 62-year-old Connecticut-based attorney asked if he could stay on it. A year ago Cantor’s wife, Shari, who is mayor of West Hartford, Conn., started to take metformin, too.
“I read the articles, they made a lot of sense to me, and with the number of people that have been taking this drug worldwide for decades, I felt like there was nothing to lose,” he says.
The couple can’t say if their daily doses have led to any changes in how they look or feel. After all, they’re taking the pills not to treat current ailments but to prevent ones in the future.
They may have answers soon. Nir Barzilai, MD, director of the National Institutes of Health’s Nathan Shock Centers of Excellence in the Basic Biology of Aging, is leading a study that hopes to prove aging is a preventable health condition. The TAME (Targeting Aging with Metformin) study is designed to do this by demonstrating that metformin, a cheap and widely prescribed pill for diabetes, may also be an anti-aging elixir.
The TAME trial is currently in phase III – typically the final step of research into any treatment before drugmakers can apply for FDA approval.
Earlier studies found that people with type 2 diabetes who take metformin have lower death rates from any cause, compared to peers who don’t take the drug. Metformin also seems to help curb the incidence of age-related diseases, including heart disease, dementia, and Alzheimer›s. It also may lower the risk of many types of cancer as well as raise the chances of survival. Observations made since the beginning of the COVID-19 pandemic suggest that people who get the virus while taking metformin are less likely to land in the hospital or die from it.
It’s not clear exactly how metformin works to do all that. The compound was originally derived from Galega officinalis, also known as goat’s rue, a perennial plant used as medicine since medieval times.
Dr. Barzilai says he hopes to prove that aging is a preventable condition.
“If the results are what they think they will be, the whole world could go on metformin and extend life for everybody – extend your good quality of life,” Dr. Barzilai says. “That’s what we all want. Every extra year that we could get where we’re still vigorous and vital would be amazing.”
Long life versus healthy life
Some researchers argue that only the “healthspan” – the period of life free of illness – is worth extending. Of course, a healthy lifestyle can add years to most people’s lives and actually improve cellular aging. Some of the biggest payoffs come from quitting or never smoking, logging more than 5½ hours of physical activity per week, and keeping a normal weight.
Drugs may be able to do that as well by interrupting common markers of aging, including telomere length, inflammation, oxidative stress, and slower cell metabolism.
“You don’t have to target all of these hallmarks to get improvement” in healthspans, says Dr. Barzilai, who also is director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx and scientific director of the American Federation for Aging Research.
“If you target one, you show benefit in the others.”
The medical term for growing old is senescence. Buffeted by DNA damage and stresses, your cells deteriorate and eventually stop multiplying, but don’t die.
That slowdown may have big consequences for your health. Your genes become more likely to get mutations, which can pave the way for cancer. Mitochondria, which produce energy in the cell, struggle to fuel your body. That can damage cells and cause chronic inflammation, which plays a part in diabetes, arthritis, ulcerative colitis, and many other diseases.
One major hallmark of aging is the growing stockpile of these senescent cells. Damaged cells become deactivated as a way to protect your body from harmful or uncontrolled cell division. But like the rotten apple that spoils the whole bunch, senescent cells encourage their neighbors to turn dysfunctional, too. They also emit proteins that trigger inflammation. Your body naturally removes these dormant cells. But older immune systems have a harder time cleaning up, so the senescent cells are more likely to hang around.
Flushing out this accumulated debris may be one way to avert aging, some experts say.
Dr. De Grey also believes that could be done with drugs.
“These therapies would actually repair [cellular] damage,” he says. “They’ll eliminate damage from the body by resetting or turning back the clock.”
James Kirkland, MD, PhD, of the Mayo Clinic, is one researcher exploring this theory. He gave a mixture of the cancer drug dasatinib and a plant pigment called quercetin to people with diabetic kidney disease. Quercetin is an antioxidant that gives grapes, tomatoes, and other fruits and vegetables their flavor.
A small phase I clinical trial showed that the dasatinib-quercetin combination got rid of senescent cells in the tissues of people with the disease.
The researchers don’t know yet if the results will translate into prolonged youth. They also don’t know how high a dosage is needed and what long-term problems the treatment might cause. People with chronic leukemia take dasatinib for years with few serious ill effects.
In another recent study, scientists used oxygen therapy to tackle senescent cells. Thirty-five adults ages 64 and older received oxygen therapy in a pressurized chamber. After 60 daily sessions, they showed a decrease in senescent cells and improvement in the length of DNA segments called telomeres. Shortened segments of telomeres are thought to be another marker of aging.
Researchers are also looking to the gene-editing technology CRISPR for anti-aging treatments, but the testing is only in mice so far.
Dr. Barzilai hopes that if the metformin trial succeeds, it will open the floodgates to a wave of new drugs that can stop or reverse human aging. Some of the major players in this field include Juvenescence, AgeX Therapeutics, LyGenesis, and Life Biosciences, which Dr. Barzilai founded.
“Until aging is seen as preventable, health plans won’t have to pay for this type of treatment,” he says. And if health plans won’t cover aging, pharmaceutical companies have little incentive to invest in drug development.
That may be the only thing standing between humans and unprecedented lifespans. The Census Bureau projects that Americans born in 2060 should live an average of 85.6 years, up from 78.7 years in 2018. Dr. De Grey’s prediction tops that mark by a factor of about 50. He believes that the life expectancy for someone born in 2100 may well be 5,000 years.
Dr. Barzilai, for his part, has a prediction that’s seemingly more modest.
“We die at 80. Getting an additional 35 years is relatively low-hanging fruit,” he says. “But I don’t believe that is a fixed limit.”
A version of this article first appeared on WebMD.com.
Heart disease. Cancer. Diabetes. Dementia.
Researchers spend billions of dollars every year trying to eradicate these medical scourges.
Yet even if we discover cures to these and all other chronic conditions, it won’t change our ultimate prognosis: death.
“That’s because you haven’t stopped aging,” says Jay Olshansky, PhD, a professor of epidemiology and biostatistics at the University of Illinois at Chicago School of Public Health.
But what if we could?
Some scientists think so. Fueled in part by a billion dollars of investor money, they are attempting to reverse-engineer your molecular biological clock. Their goal? To eliminate not merely diseases that kill people, but to prevent death itself.
Hacking the code for immortality
Aubrey de Grey, PhD, a biomedical gerontologist, has drawn wide attention for his belief that the first person who will live to be 1,000 years old is already among us.
He believes there’s no cap on how long we can live, depending on what medicines we develop in the future.
“The whole idea is that there would not be a limit on how long we can keep people healthy,” Dr. de Grey says. He’s the chief science officer and co-founder of the SENS Research Foundation, which funds research on how to put the brakes on aging.
Dr. De Grey’s view, in theory, isn’t so far-fetched.
Scientists have studied the immortal jellyfish, Turritopsis dohrnii. It’s the only animal that can cheat death by reverting from adulthood back to its polyp stage when threatened with danger or starvation.
Other clues to possible eternal life also may exist underwater. Certain marine clams can live more than 500 years. And lobsters stock a seemingly limitless supply of a youthful enzyme that has some scientists wondering if the crustacean, under the best conditions, just might live forever.
Among humans, researchers have been studying “super-agers” – people who not only live exceptionally long, but also do so without many of the chronic diseases that plague their peers. That’s even though they share some of the same bad habits as everyone else.
“They are making it past the age of 80 with their minds completely intact. That’s what’s so unusual,” Dr. Olshansky says. The rest of their bodies are doing better than those of average 80-year-olds, too.
People who reached ages 95 to 112 got cancer, heart disease, diabetes, osteoporosis, and stroke up to 24 years later than those with average lifespans, data show. Figuring out why might pave the way for targeted gene therapy to mimic the DNA of these nonagenarians and centenarians.
“There’s likely to be secrets contained within their genome that are eventually discovered that will help us develop therapeutic interventions to mimic the effects of decelerated aging,” Dr. Olshansky says.
Treating aging this way may offer a bigger payoff than targeting individual diseases. That’s because even if you manage to dodge any illnesses, there’s ultimately no escaping old age.
“Longevity is a side effect of health,” Dr. de Grey says. “If we can keep people healthy, then their likelihood of dying is reduced.”
Aging as a preventable condition
In 2015, Michael Cantor was prescribed metformin for prediabetes. Once that was under control, his doctor said Mr. Cantor could quit the drug. But Mr. Cantor had heard about studies testing it as an anti-aging drug. The 62-year-old Connecticut-based attorney asked if he could stay on it. A year ago Cantor’s wife, Shari, who is mayor of West Hartford, Conn., started to take metformin, too.
“I read the articles, they made a lot of sense to me, and with the number of people that have been taking this drug worldwide for decades, I felt like there was nothing to lose,” he says.
The couple can’t say if their daily doses have led to any changes in how they look or feel. After all, they’re taking the pills not to treat current ailments but to prevent ones in the future.
They may have answers soon. Nir Barzilai, MD, director of the National Institutes of Health’s Nathan Shock Centers of Excellence in the Basic Biology of Aging, is leading a study that hopes to prove aging is a preventable health condition. The TAME (Targeting Aging with Metformin) study is designed to do this by demonstrating that metformin, a cheap and widely prescribed pill for diabetes, may also be an anti-aging elixir.
The TAME trial is currently in phase III – typically the final step of research into any treatment before drugmakers can apply for FDA approval.
Earlier studies found that people with type 2 diabetes who take metformin have lower death rates from any cause, compared to peers who don’t take the drug. Metformin also seems to help curb the incidence of age-related diseases, including heart disease, dementia, and Alzheimer›s. It also may lower the risk of many types of cancer as well as raise the chances of survival. Observations made since the beginning of the COVID-19 pandemic suggest that people who get the virus while taking metformin are less likely to land in the hospital or die from it.
It’s not clear exactly how metformin works to do all that. The compound was originally derived from Galega officinalis, also known as goat’s rue, a perennial plant used as medicine since medieval times.
Dr. Barzilai says he hopes to prove that aging is a preventable condition.
“If the results are what they think they will be, the whole world could go on metformin and extend life for everybody – extend your good quality of life,” Dr. Barzilai says. “That’s what we all want. Every extra year that we could get where we’re still vigorous and vital would be amazing.”
Long life versus healthy life
Some researchers argue that only the “healthspan” – the period of life free of illness – is worth extending. Of course, a healthy lifestyle can add years to most people’s lives and actually improve cellular aging. Some of the biggest payoffs come from quitting or never smoking, logging more than 5½ hours of physical activity per week, and keeping a normal weight.
Drugs may be able to do that as well by interrupting common markers of aging, including telomere length, inflammation, oxidative stress, and slower cell metabolism.
“You don’t have to target all of these hallmarks to get improvement” in healthspans, says Dr. Barzilai, who also is director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx and scientific director of the American Federation for Aging Research.
“If you target one, you show benefit in the others.”
The medical term for growing old is senescence. Buffeted by DNA damage and stresses, your cells deteriorate and eventually stop multiplying, but don’t die.
That slowdown may have big consequences for your health. Your genes become more likely to get mutations, which can pave the way for cancer. Mitochondria, which produce energy in the cell, struggle to fuel your body. That can damage cells and cause chronic inflammation, which plays a part in diabetes, arthritis, ulcerative colitis, and many other diseases.
One major hallmark of aging is the growing stockpile of these senescent cells. Damaged cells become deactivated as a way to protect your body from harmful or uncontrolled cell division. But like the rotten apple that spoils the whole bunch, senescent cells encourage their neighbors to turn dysfunctional, too. They also emit proteins that trigger inflammation. Your body naturally removes these dormant cells. But older immune systems have a harder time cleaning up, so the senescent cells are more likely to hang around.
Flushing out this accumulated debris may be one way to avert aging, some experts say.
Dr. De Grey also believes that could be done with drugs.
“These therapies would actually repair [cellular] damage,” he says. “They’ll eliminate damage from the body by resetting or turning back the clock.”
James Kirkland, MD, PhD, of the Mayo Clinic, is one researcher exploring this theory. He gave a mixture of the cancer drug dasatinib and a plant pigment called quercetin to people with diabetic kidney disease. Quercetin is an antioxidant that gives grapes, tomatoes, and other fruits and vegetables their flavor.
A small phase I clinical trial showed that the dasatinib-quercetin combination got rid of senescent cells in the tissues of people with the disease.
The researchers don’t know yet if the results will translate into prolonged youth. They also don’t know how high a dosage is needed and what long-term problems the treatment might cause. People with chronic leukemia take dasatinib for years with few serious ill effects.
In another recent study, scientists used oxygen therapy to tackle senescent cells. Thirty-five adults ages 64 and older received oxygen therapy in a pressurized chamber. After 60 daily sessions, they showed a decrease in senescent cells and improvement in the length of DNA segments called telomeres. Shortened segments of telomeres are thought to be another marker of aging.
Researchers are also looking to the gene-editing technology CRISPR for anti-aging treatments, but the testing is only in mice so far.
Dr. Barzilai hopes that if the metformin trial succeeds, it will open the floodgates to a wave of new drugs that can stop or reverse human aging. Some of the major players in this field include Juvenescence, AgeX Therapeutics, LyGenesis, and Life Biosciences, which Dr. Barzilai founded.
“Until aging is seen as preventable, health plans won’t have to pay for this type of treatment,” he says. And if health plans won’t cover aging, pharmaceutical companies have little incentive to invest in drug development.
That may be the only thing standing between humans and unprecedented lifespans. The Census Bureau projects that Americans born in 2060 should live an average of 85.6 years, up from 78.7 years in 2018. Dr. De Grey’s prediction tops that mark by a factor of about 50. He believes that the life expectancy for someone born in 2100 may well be 5,000 years.
Dr. Barzilai, for his part, has a prediction that’s seemingly more modest.
“We die at 80. Getting an additional 35 years is relatively low-hanging fruit,” he says. “But I don’t believe that is a fixed limit.”
A version of this article first appeared on WebMD.com.
Heart disease. Cancer. Diabetes. Dementia.
Researchers spend billions of dollars every year trying to eradicate these medical scourges.
Yet even if we discover cures to these and all other chronic conditions, it won’t change our ultimate prognosis: death.
“That’s because you haven’t stopped aging,” says Jay Olshansky, PhD, a professor of epidemiology and biostatistics at the University of Illinois at Chicago School of Public Health.
But what if we could?
Some scientists think so. Fueled in part by a billion dollars of investor money, they are attempting to reverse-engineer your molecular biological clock. Their goal? To eliminate not merely diseases that kill people, but to prevent death itself.
Hacking the code for immortality
Aubrey de Grey, PhD, a biomedical gerontologist, has drawn wide attention for his belief that the first person who will live to be 1,000 years old is already among us.
He believes there’s no cap on how long we can live, depending on what medicines we develop in the future.
“The whole idea is that there would not be a limit on how long we can keep people healthy,” Dr. de Grey says. He’s the chief science officer and co-founder of the SENS Research Foundation, which funds research on how to put the brakes on aging.
Dr. De Grey’s view, in theory, isn’t so far-fetched.
Scientists have studied the immortal jellyfish, Turritopsis dohrnii. It’s the only animal that can cheat death by reverting from adulthood back to its polyp stage when threatened with danger or starvation.
Other clues to possible eternal life also may exist underwater. Certain marine clams can live more than 500 years. And lobsters stock a seemingly limitless supply of a youthful enzyme that has some scientists wondering if the crustacean, under the best conditions, just might live forever.
Among humans, researchers have been studying “super-agers” – people who not only live exceptionally long, but also do so without many of the chronic diseases that plague their peers. That’s even though they share some of the same bad habits as everyone else.
“They are making it past the age of 80 with their minds completely intact. That’s what’s so unusual,” Dr. Olshansky says. The rest of their bodies are doing better than those of average 80-year-olds, too.
People who reached ages 95 to 112 got cancer, heart disease, diabetes, osteoporosis, and stroke up to 24 years later than those with average lifespans, data show. Figuring out why might pave the way for targeted gene therapy to mimic the DNA of these nonagenarians and centenarians.
“There’s likely to be secrets contained within their genome that are eventually discovered that will help us develop therapeutic interventions to mimic the effects of decelerated aging,” Dr. Olshansky says.
Treating aging this way may offer a bigger payoff than targeting individual diseases. That’s because even if you manage to dodge any illnesses, there’s ultimately no escaping old age.
“Longevity is a side effect of health,” Dr. de Grey says. “If we can keep people healthy, then their likelihood of dying is reduced.”
Aging as a preventable condition
In 2015, Michael Cantor was prescribed metformin for prediabetes. Once that was under control, his doctor said Mr. Cantor could quit the drug. But Mr. Cantor had heard about studies testing it as an anti-aging drug. The 62-year-old Connecticut-based attorney asked if he could stay on it. A year ago Cantor’s wife, Shari, who is mayor of West Hartford, Conn., started to take metformin, too.
“I read the articles, they made a lot of sense to me, and with the number of people that have been taking this drug worldwide for decades, I felt like there was nothing to lose,” he says.
The couple can’t say if their daily doses have led to any changes in how they look or feel. After all, they’re taking the pills not to treat current ailments but to prevent ones in the future.
They may have answers soon. Nir Barzilai, MD, director of the National Institutes of Health’s Nathan Shock Centers of Excellence in the Basic Biology of Aging, is leading a study that hopes to prove aging is a preventable health condition. The TAME (Targeting Aging with Metformin) study is designed to do this by demonstrating that metformin, a cheap and widely prescribed pill for diabetes, may also be an anti-aging elixir.
The TAME trial is currently in phase III – typically the final step of research into any treatment before drugmakers can apply for FDA approval.
Earlier studies found that people with type 2 diabetes who take metformin have lower death rates from any cause, compared to peers who don’t take the drug. Metformin also seems to help curb the incidence of age-related diseases, including heart disease, dementia, and Alzheimer›s. It also may lower the risk of many types of cancer as well as raise the chances of survival. Observations made since the beginning of the COVID-19 pandemic suggest that people who get the virus while taking metformin are less likely to land in the hospital or die from it.
It’s not clear exactly how metformin works to do all that. The compound was originally derived from Galega officinalis, also known as goat’s rue, a perennial plant used as medicine since medieval times.
Dr. Barzilai says he hopes to prove that aging is a preventable condition.
“If the results are what they think they will be, the whole world could go on metformin and extend life for everybody – extend your good quality of life,” Dr. Barzilai says. “That’s what we all want. Every extra year that we could get where we’re still vigorous and vital would be amazing.”
Long life versus healthy life
Some researchers argue that only the “healthspan” – the period of life free of illness – is worth extending. Of course, a healthy lifestyle can add years to most people’s lives and actually improve cellular aging. Some of the biggest payoffs come from quitting or never smoking, logging more than 5½ hours of physical activity per week, and keeping a normal weight.
Drugs may be able to do that as well by interrupting common markers of aging, including telomere length, inflammation, oxidative stress, and slower cell metabolism.
“You don’t have to target all of these hallmarks to get improvement” in healthspans, says Dr. Barzilai, who also is director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx and scientific director of the American Federation for Aging Research.
“If you target one, you show benefit in the others.”
The medical term for growing old is senescence. Buffeted by DNA damage and stresses, your cells deteriorate and eventually stop multiplying, but don’t die.
That slowdown may have big consequences for your health. Your genes become more likely to get mutations, which can pave the way for cancer. Mitochondria, which produce energy in the cell, struggle to fuel your body. That can damage cells and cause chronic inflammation, which plays a part in diabetes, arthritis, ulcerative colitis, and many other diseases.
One major hallmark of aging is the growing stockpile of these senescent cells. Damaged cells become deactivated as a way to protect your body from harmful or uncontrolled cell division. But like the rotten apple that spoils the whole bunch, senescent cells encourage their neighbors to turn dysfunctional, too. They also emit proteins that trigger inflammation. Your body naturally removes these dormant cells. But older immune systems have a harder time cleaning up, so the senescent cells are more likely to hang around.
Flushing out this accumulated debris may be one way to avert aging, some experts say.
Dr. De Grey also believes that could be done with drugs.
“These therapies would actually repair [cellular] damage,” he says. “They’ll eliminate damage from the body by resetting or turning back the clock.”
James Kirkland, MD, PhD, of the Mayo Clinic, is one researcher exploring this theory. He gave a mixture of the cancer drug dasatinib and a plant pigment called quercetin to people with diabetic kidney disease. Quercetin is an antioxidant that gives grapes, tomatoes, and other fruits and vegetables their flavor.
A small phase I clinical trial showed that the dasatinib-quercetin combination got rid of senescent cells in the tissues of people with the disease.
The researchers don’t know yet if the results will translate into prolonged youth. They also don’t know how high a dosage is needed and what long-term problems the treatment might cause. People with chronic leukemia take dasatinib for years with few serious ill effects.
In another recent study, scientists used oxygen therapy to tackle senescent cells. Thirty-five adults ages 64 and older received oxygen therapy in a pressurized chamber. After 60 daily sessions, they showed a decrease in senescent cells and improvement in the length of DNA segments called telomeres. Shortened segments of telomeres are thought to be another marker of aging.
Researchers are also looking to the gene-editing technology CRISPR for anti-aging treatments, but the testing is only in mice so far.
Dr. Barzilai hopes that if the metformin trial succeeds, it will open the floodgates to a wave of new drugs that can stop or reverse human aging. Some of the major players in this field include Juvenescence, AgeX Therapeutics, LyGenesis, and Life Biosciences, which Dr. Barzilai founded.
“Until aging is seen as preventable, health plans won’t have to pay for this type of treatment,” he says. And if health plans won’t cover aging, pharmaceutical companies have little incentive to invest in drug development.
That may be the only thing standing between humans and unprecedented lifespans. The Census Bureau projects that Americans born in 2060 should live an average of 85.6 years, up from 78.7 years in 2018. Dr. De Grey’s prediction tops that mark by a factor of about 50. He believes that the life expectancy for someone born in 2100 may well be 5,000 years.
Dr. Barzilai, for his part, has a prediction that’s seemingly more modest.
“We die at 80. Getting an additional 35 years is relatively low-hanging fruit,” he says. “But I don’t believe that is a fixed limit.”
A version of this article first appeared on WebMD.com.
Rapid Desensitization after a Type I Hypersensitivity Reaction to Ceftazidime/Avibactam
Cerebral palsy (CP) embodies a collection of disorders involving permanent but nonprogressive motor dysfunction secondary to one of a variety of abnormal disturbances that can occur in the developing fetal or infantile brain.1 The motor impairment of CP classically leads to irregularities in muscle tone, posture, and/or movement, resulting in limitations of functional abilities that vary in severity.1,2 Patients with CP commonly experience dysphagia, gastroesophageal reflux disease, impaired airway clearance, chest wall and spine deformities, restrictive lung disease, and/or recurrent aspiration.1 Consequently, pulmonary disease is the leading cause of morbidity and mortality in patients with severe CP, characterized by recurrent bacterial infections.3,4
Frequent antibiotic use increases the risk of multidrug-resistant pathogen formation and hypersensitivity to antibiotics. Life-threatening allergic reactions in a patient population with impaired lung function significantly complicates patient management, often leading to suboptimal treatment with second-line agents.5 This case study describes a previously penicillin-tolerant patient with CP who developed a type I hypersensitivity reaction to ceftazidime/avibactam and was treated successfully with the antibiotic after rapid induction of temporary tolerance.
Case Presentation
A 34-year-old male with a complex medical history of severe spastic CP and atonic seizures was recently diagnosed with adenocarcinoma of the colon and admitted for ileostomy and sigmoidectomy. The surgery was complicated by spillage of intestinal contents into the peritoneal cavity 3 days postoperation. The patient was urgently taken to the operating room for exploratory laparotomy, culminating in remaining colectomy, complete abdominal washout, and wound vacuum placement. He continued to deteriorate clinically over the next few weeks, beginning with the development of feculent peritonitis and septic shock. Respiratory distress ensued, and the patient required a tracheostomy with mechanical ventilation. A computed tomography of the chest was consistent with multifocal pneumonia, and a respiratory culture of bronchioalveolar lavage fluid cultivated Klebsiella pneumoniae, a carbapenem-resistant Enterobacteriaceae.
The infectious disease service was consulted and recommended ceftazidime/avibactam as the only acceptable antibiotic to treat this organism. The patient had no history of drug hypersensitivities. However, he developed diffuse, generalized urticaria and predominately right-sided flushing immediately following the onset of the antibiotic infusion. The urticaria was pruritic. The patient did not have angioedema, and he did not experience any adverse respiratory, cardiac, gastrointestinal, or neurologic symptoms. The infusion was ceased immediately, and the patient was treated with a combination of diphenhydramine 50 mg IV and ranitidine 50 mg IV. Resolution of his hypersensitivity symptoms occurred within an hour of treatment, and vital signs remained stable with no resurgence of symptoms. At the time of his reaction, the patient also was taking pantoprazole, valproate, metoprolol, risperidone, and oxycodone as needed for pain. A tryptase level was not measured.
The allergy and immunology service was consulted for rapid desensitization to ceftazidime/avibactam as the culture and sensitivity test demonstrated the bacterium to be resistant to alternative antibiotics. Skin testing to ceftazidime/avibactam was deferred at the time due to the patient’s critical illness. The patient was premedicated with diphenhydramine and ranitidine 50 mg IV. Rapid IV desensitization was performed using a standard 12-step protocol developed for chemotherapeutic agents but demonstrated as safe and effective when applied to antibiotics in patients with cystic fibrosis.5 The antibiotic was administered in sequential 15-minute intervals for a total of 12 progressively doubled doses with continuous monitoring for the appearance of allergic reactions (Table). The target dose of 2.5 g was successfully achieved, and the patient tolerated a complete 14-day treatment regimen with no further adverse reactions to the medication. During the remainder of his hospital admission, the patient improved significantly without further complications.
Discussion
This is the first reported case in the literature to describe a type I hypersensitivity reaction with rapid IV induction of tolerance to ceftazidime/avibactam. We describe his reaction as type I hypersensitivity because the patient developed immediate generalized urticaria and flushing. Use of a safe desensitization protocol, demonstrated in this case report, is paramount to optimal management of infections in patient populations with severely decreased lung function, such as CP.5-7 It provides a safe and effective technique to maintain patients on first line, preferred therapy, despite their increased risk of potentially life-threatening allergic reactions.
Interestingly, this patient previously tolerated penicillins and cephalosporins without adverse reactions, suggesting the possibility of a non–IgE-mediated vs an IgE-mediated mechanism to the hypersensitivity reaction. The patient also was receiving oxycodone at the time of his reaction, and oxycodone can cause nonspecific mast cell degranulation. Additional information from skin testing to ceftazidime/avibactam could help determine whether the patient had an IgE-mediated hypersensitivity reaction. This information could help clarify the culprit agent and guide further avoidance recommendations.
Unfortunately, because the patient was critically ill, skin testing was not performed, and he underwent an urgent antibiotic desensitization with success. It was recommended that the patient follow up in the allergy and immunology clinic for further evaluation with skin testing to ceftazidime/avibactam as well as other β-lactams to determine his future risk of reaction. Unfortunately, he was lost to follow-up.
Frequent IV antibiotic use is a risk factor for the development of antibiotic allergies.8,9 This patient had received many prior courses of IV antibiotics, and this factor most likely contributed to his immediate hypersensitivity reaction to ceftazidime/avibactam. Fortunately, he tolerated a rapid induction of tolerance.
As life expectancies for patients with chronic medical conditions that involve recurrent infections increase, the associated emergence of multidrug-resistant pathogens and necessity for use of novel combination antibiotics should prompt further investigation of nonirritating doses of these drugs for skin testing in the case of drug hypersensitivities. This information would be essential for skin prick testing and determination of whether patients have a true IgE-mediated reaction to these antibiotics.
Conclusions
This is the first case report demonstrating a successful rapid induction of tolerance for the antibiotic ceftazidime/avibactam. Fortunately, the patient tolerated the desensitization procedure without further adverse reactions, and he had a resolution of his infection.
1. Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol. 2007;109:8-14.
2. Haak P, Lenski M, Hidecker MJ, et al. Cerebral palsy and aging. Dev Med Child Neurol. 2009;51(suppl 4):16-23. doi:10.1111/j.1469-8749.2009.03428.x
3. Duruflé-Tapin A, Colin A, Nicolas B, Lebreton C, Dauvergne F, Gallien P. Analysis of the medical causes of death in cerebral palsy. Ann Phys Rehabil Med. 2014;57(1):24-37. doi:10.1016/j.rehab.2013.11.002
4. Boel L, Pernet K, Toussaint M, et al. Respiratory morbidity in children with cerebral palsy: an overview. Dev Med Child Neurol. 2019;61(6):646-653. doi:10.1111/dmcn.14060
5. Legere HJ 3rd, Palis RI, Rodriguez Bouza T, Uluer AZ, Castells MC. A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros. 2009;8(6):418-424. doi:10.1016/j.jcf.2009.08.002
6. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am. 2009;29(3):585-606. doi:10.1016/j.iac.2009.04.012
7. Liu A, Fanning L, Chong H, et al. Desensitization regimens for drug allergy: state of the art in the 21st century. Clin Exp Allergy. 2011;41(12):1679-1689. doi:10.1111/j.1365-2222.2011.03825.x
8. Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol. 2011;71(5):684-700. doi:10.1111/j.1365-2125.2010.03774.x
9. Adkinson NF Jr. Risk factors for drug allergy. J Allergy Clin Immunol. 1984;74(4, pt 2):567-572. doi:10.1016/0091-6749(84)90108-8
Cerebral palsy (CP) embodies a collection of disorders involving permanent but nonprogressive motor dysfunction secondary to one of a variety of abnormal disturbances that can occur in the developing fetal or infantile brain.1 The motor impairment of CP classically leads to irregularities in muscle tone, posture, and/or movement, resulting in limitations of functional abilities that vary in severity.1,2 Patients with CP commonly experience dysphagia, gastroesophageal reflux disease, impaired airway clearance, chest wall and spine deformities, restrictive lung disease, and/or recurrent aspiration.1 Consequently, pulmonary disease is the leading cause of morbidity and mortality in patients with severe CP, characterized by recurrent bacterial infections.3,4
Frequent antibiotic use increases the risk of multidrug-resistant pathogen formation and hypersensitivity to antibiotics. Life-threatening allergic reactions in a patient population with impaired lung function significantly complicates patient management, often leading to suboptimal treatment with second-line agents.5 This case study describes a previously penicillin-tolerant patient with CP who developed a type I hypersensitivity reaction to ceftazidime/avibactam and was treated successfully with the antibiotic after rapid induction of temporary tolerance.
Case Presentation
A 34-year-old male with a complex medical history of severe spastic CP and atonic seizures was recently diagnosed with adenocarcinoma of the colon and admitted for ileostomy and sigmoidectomy. The surgery was complicated by spillage of intestinal contents into the peritoneal cavity 3 days postoperation. The patient was urgently taken to the operating room for exploratory laparotomy, culminating in remaining colectomy, complete abdominal washout, and wound vacuum placement. He continued to deteriorate clinically over the next few weeks, beginning with the development of feculent peritonitis and septic shock. Respiratory distress ensued, and the patient required a tracheostomy with mechanical ventilation. A computed tomography of the chest was consistent with multifocal pneumonia, and a respiratory culture of bronchioalveolar lavage fluid cultivated Klebsiella pneumoniae, a carbapenem-resistant Enterobacteriaceae.
The infectious disease service was consulted and recommended ceftazidime/avibactam as the only acceptable antibiotic to treat this organism. The patient had no history of drug hypersensitivities. However, he developed diffuse, generalized urticaria and predominately right-sided flushing immediately following the onset of the antibiotic infusion. The urticaria was pruritic. The patient did not have angioedema, and he did not experience any adverse respiratory, cardiac, gastrointestinal, or neurologic symptoms. The infusion was ceased immediately, and the patient was treated with a combination of diphenhydramine 50 mg IV and ranitidine 50 mg IV. Resolution of his hypersensitivity symptoms occurred within an hour of treatment, and vital signs remained stable with no resurgence of symptoms. At the time of his reaction, the patient also was taking pantoprazole, valproate, metoprolol, risperidone, and oxycodone as needed for pain. A tryptase level was not measured.
The allergy and immunology service was consulted for rapid desensitization to ceftazidime/avibactam as the culture and sensitivity test demonstrated the bacterium to be resistant to alternative antibiotics. Skin testing to ceftazidime/avibactam was deferred at the time due to the patient’s critical illness. The patient was premedicated with diphenhydramine and ranitidine 50 mg IV. Rapid IV desensitization was performed using a standard 12-step protocol developed for chemotherapeutic agents but demonstrated as safe and effective when applied to antibiotics in patients with cystic fibrosis.5 The antibiotic was administered in sequential 15-minute intervals for a total of 12 progressively doubled doses with continuous monitoring for the appearance of allergic reactions (Table). The target dose of 2.5 g was successfully achieved, and the patient tolerated a complete 14-day treatment regimen with no further adverse reactions to the medication. During the remainder of his hospital admission, the patient improved significantly without further complications.
Discussion
This is the first reported case in the literature to describe a type I hypersensitivity reaction with rapid IV induction of tolerance to ceftazidime/avibactam. We describe his reaction as type I hypersensitivity because the patient developed immediate generalized urticaria and flushing. Use of a safe desensitization protocol, demonstrated in this case report, is paramount to optimal management of infections in patient populations with severely decreased lung function, such as CP.5-7 It provides a safe and effective technique to maintain patients on first line, preferred therapy, despite their increased risk of potentially life-threatening allergic reactions.
Interestingly, this patient previously tolerated penicillins and cephalosporins without adverse reactions, suggesting the possibility of a non–IgE-mediated vs an IgE-mediated mechanism to the hypersensitivity reaction. The patient also was receiving oxycodone at the time of his reaction, and oxycodone can cause nonspecific mast cell degranulation. Additional information from skin testing to ceftazidime/avibactam could help determine whether the patient had an IgE-mediated hypersensitivity reaction. This information could help clarify the culprit agent and guide further avoidance recommendations.
Unfortunately, because the patient was critically ill, skin testing was not performed, and he underwent an urgent antibiotic desensitization with success. It was recommended that the patient follow up in the allergy and immunology clinic for further evaluation with skin testing to ceftazidime/avibactam as well as other β-lactams to determine his future risk of reaction. Unfortunately, he was lost to follow-up.
Frequent IV antibiotic use is a risk factor for the development of antibiotic allergies.8,9 This patient had received many prior courses of IV antibiotics, and this factor most likely contributed to his immediate hypersensitivity reaction to ceftazidime/avibactam. Fortunately, he tolerated a rapid induction of tolerance.
As life expectancies for patients with chronic medical conditions that involve recurrent infections increase, the associated emergence of multidrug-resistant pathogens and necessity for use of novel combination antibiotics should prompt further investigation of nonirritating doses of these drugs for skin testing in the case of drug hypersensitivities. This information would be essential for skin prick testing and determination of whether patients have a true IgE-mediated reaction to these antibiotics.
Conclusions
This is the first case report demonstrating a successful rapid induction of tolerance for the antibiotic ceftazidime/avibactam. Fortunately, the patient tolerated the desensitization procedure without further adverse reactions, and he had a resolution of his infection.
Cerebral palsy (CP) embodies a collection of disorders involving permanent but nonprogressive motor dysfunction secondary to one of a variety of abnormal disturbances that can occur in the developing fetal or infantile brain.1 The motor impairment of CP classically leads to irregularities in muscle tone, posture, and/or movement, resulting in limitations of functional abilities that vary in severity.1,2 Patients with CP commonly experience dysphagia, gastroesophageal reflux disease, impaired airway clearance, chest wall and spine deformities, restrictive lung disease, and/or recurrent aspiration.1 Consequently, pulmonary disease is the leading cause of morbidity and mortality in patients with severe CP, characterized by recurrent bacterial infections.3,4
Frequent antibiotic use increases the risk of multidrug-resistant pathogen formation and hypersensitivity to antibiotics. Life-threatening allergic reactions in a patient population with impaired lung function significantly complicates patient management, often leading to suboptimal treatment with second-line agents.5 This case study describes a previously penicillin-tolerant patient with CP who developed a type I hypersensitivity reaction to ceftazidime/avibactam and was treated successfully with the antibiotic after rapid induction of temporary tolerance.
Case Presentation
A 34-year-old male with a complex medical history of severe spastic CP and atonic seizures was recently diagnosed with adenocarcinoma of the colon and admitted for ileostomy and sigmoidectomy. The surgery was complicated by spillage of intestinal contents into the peritoneal cavity 3 days postoperation. The patient was urgently taken to the operating room for exploratory laparotomy, culminating in remaining colectomy, complete abdominal washout, and wound vacuum placement. He continued to deteriorate clinically over the next few weeks, beginning with the development of feculent peritonitis and septic shock. Respiratory distress ensued, and the patient required a tracheostomy with mechanical ventilation. A computed tomography of the chest was consistent with multifocal pneumonia, and a respiratory culture of bronchioalveolar lavage fluid cultivated Klebsiella pneumoniae, a carbapenem-resistant Enterobacteriaceae.
The infectious disease service was consulted and recommended ceftazidime/avibactam as the only acceptable antibiotic to treat this organism. The patient had no history of drug hypersensitivities. However, he developed diffuse, generalized urticaria and predominately right-sided flushing immediately following the onset of the antibiotic infusion. The urticaria was pruritic. The patient did not have angioedema, and he did not experience any adverse respiratory, cardiac, gastrointestinal, or neurologic symptoms. The infusion was ceased immediately, and the patient was treated with a combination of diphenhydramine 50 mg IV and ranitidine 50 mg IV. Resolution of his hypersensitivity symptoms occurred within an hour of treatment, and vital signs remained stable with no resurgence of symptoms. At the time of his reaction, the patient also was taking pantoprazole, valproate, metoprolol, risperidone, and oxycodone as needed for pain. A tryptase level was not measured.
The allergy and immunology service was consulted for rapid desensitization to ceftazidime/avibactam as the culture and sensitivity test demonstrated the bacterium to be resistant to alternative antibiotics. Skin testing to ceftazidime/avibactam was deferred at the time due to the patient’s critical illness. The patient was premedicated with diphenhydramine and ranitidine 50 mg IV. Rapid IV desensitization was performed using a standard 12-step protocol developed for chemotherapeutic agents but demonstrated as safe and effective when applied to antibiotics in patients with cystic fibrosis.5 The antibiotic was administered in sequential 15-minute intervals for a total of 12 progressively doubled doses with continuous monitoring for the appearance of allergic reactions (Table). The target dose of 2.5 g was successfully achieved, and the patient tolerated a complete 14-day treatment regimen with no further adverse reactions to the medication. During the remainder of his hospital admission, the patient improved significantly without further complications.
Discussion
This is the first reported case in the literature to describe a type I hypersensitivity reaction with rapid IV induction of tolerance to ceftazidime/avibactam. We describe his reaction as type I hypersensitivity because the patient developed immediate generalized urticaria and flushing. Use of a safe desensitization protocol, demonstrated in this case report, is paramount to optimal management of infections in patient populations with severely decreased lung function, such as CP.5-7 It provides a safe and effective technique to maintain patients on first line, preferred therapy, despite their increased risk of potentially life-threatening allergic reactions.
Interestingly, this patient previously tolerated penicillins and cephalosporins without adverse reactions, suggesting the possibility of a non–IgE-mediated vs an IgE-mediated mechanism to the hypersensitivity reaction. The patient also was receiving oxycodone at the time of his reaction, and oxycodone can cause nonspecific mast cell degranulation. Additional information from skin testing to ceftazidime/avibactam could help determine whether the patient had an IgE-mediated hypersensitivity reaction. This information could help clarify the culprit agent and guide further avoidance recommendations.
Unfortunately, because the patient was critically ill, skin testing was not performed, and he underwent an urgent antibiotic desensitization with success. It was recommended that the patient follow up in the allergy and immunology clinic for further evaluation with skin testing to ceftazidime/avibactam as well as other β-lactams to determine his future risk of reaction. Unfortunately, he was lost to follow-up.
Frequent IV antibiotic use is a risk factor for the development of antibiotic allergies.8,9 This patient had received many prior courses of IV antibiotics, and this factor most likely contributed to his immediate hypersensitivity reaction to ceftazidime/avibactam. Fortunately, he tolerated a rapid induction of tolerance.
As life expectancies for patients with chronic medical conditions that involve recurrent infections increase, the associated emergence of multidrug-resistant pathogens and necessity for use of novel combination antibiotics should prompt further investigation of nonirritating doses of these drugs for skin testing in the case of drug hypersensitivities. This information would be essential for skin prick testing and determination of whether patients have a true IgE-mediated reaction to these antibiotics.
Conclusions
This is the first case report demonstrating a successful rapid induction of tolerance for the antibiotic ceftazidime/avibactam. Fortunately, the patient tolerated the desensitization procedure without further adverse reactions, and he had a resolution of his infection.
1. Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol. 2007;109:8-14.
2. Haak P, Lenski M, Hidecker MJ, et al. Cerebral palsy and aging. Dev Med Child Neurol. 2009;51(suppl 4):16-23. doi:10.1111/j.1469-8749.2009.03428.x
3. Duruflé-Tapin A, Colin A, Nicolas B, Lebreton C, Dauvergne F, Gallien P. Analysis of the medical causes of death in cerebral palsy. Ann Phys Rehabil Med. 2014;57(1):24-37. doi:10.1016/j.rehab.2013.11.002
4. Boel L, Pernet K, Toussaint M, et al. Respiratory morbidity in children with cerebral palsy: an overview. Dev Med Child Neurol. 2019;61(6):646-653. doi:10.1111/dmcn.14060
5. Legere HJ 3rd, Palis RI, Rodriguez Bouza T, Uluer AZ, Castells MC. A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros. 2009;8(6):418-424. doi:10.1016/j.jcf.2009.08.002
6. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am. 2009;29(3):585-606. doi:10.1016/j.iac.2009.04.012
7. Liu A, Fanning L, Chong H, et al. Desensitization regimens for drug allergy: state of the art in the 21st century. Clin Exp Allergy. 2011;41(12):1679-1689. doi:10.1111/j.1365-2222.2011.03825.x
8. Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol. 2011;71(5):684-700. doi:10.1111/j.1365-2125.2010.03774.x
9. Adkinson NF Jr. Risk factors for drug allergy. J Allergy Clin Immunol. 1984;74(4, pt 2):567-572. doi:10.1016/0091-6749(84)90108-8
1. Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol. 2007;109:8-14.
2. Haak P, Lenski M, Hidecker MJ, et al. Cerebral palsy and aging. Dev Med Child Neurol. 2009;51(suppl 4):16-23. doi:10.1111/j.1469-8749.2009.03428.x
3. Duruflé-Tapin A, Colin A, Nicolas B, Lebreton C, Dauvergne F, Gallien P. Analysis of the medical causes of death in cerebral palsy. Ann Phys Rehabil Med. 2014;57(1):24-37. doi:10.1016/j.rehab.2013.11.002
4. Boel L, Pernet K, Toussaint M, et al. Respiratory morbidity in children with cerebral palsy: an overview. Dev Med Child Neurol. 2019;61(6):646-653. doi:10.1111/dmcn.14060
5. Legere HJ 3rd, Palis RI, Rodriguez Bouza T, Uluer AZ, Castells MC. A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros. 2009;8(6):418-424. doi:10.1016/j.jcf.2009.08.002
6. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am. 2009;29(3):585-606. doi:10.1016/j.iac.2009.04.012
7. Liu A, Fanning L, Chong H, et al. Desensitization regimens for drug allergy: state of the art in the 21st century. Clin Exp Allergy. 2011;41(12):1679-1689. doi:10.1111/j.1365-2222.2011.03825.x
8. Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol. 2011;71(5):684-700. doi:10.1111/j.1365-2125.2010.03774.x
9. Adkinson NF Jr. Risk factors for drug allergy. J Allergy Clin Immunol. 1984;74(4, pt 2):567-572. doi:10.1016/0091-6749(84)90108-8
Chronic stress accelerates aging: Epigenetic evidence
The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”
The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.
The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:
1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.
2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
The study
In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.
The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
Results
1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.
2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.
3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
Implications
These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.
However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.
These results support the popular notion that
In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.
With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.
A version of this article first appeared on Medscape.com.
The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”
The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.
The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:
1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.
2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
The study
In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.
The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
Results
1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.
2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.
3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
Implications
These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.
However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.
These results support the popular notion that
In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.
With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.
A version of this article first appeared on Medscape.com.
The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”
The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.
The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:
1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.
2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
The study
In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.
The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
Results
1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.
2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.
3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
Implications
These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.
However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.
These results support the popular notion that
In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.
With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.
A version of this article first appeared on Medscape.com.
Why do some people escape infection that sickens others?
During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?
Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.
“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.
Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.
There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.
Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
A genetic quirk
In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.
The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.
The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.
Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.
Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.
Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
Locking out illness
“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”
Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.
Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.
The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.
“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
No norovirus
Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.
But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.
“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.
Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”
We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”
In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.
Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
Thwarting uberculosis
Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.
“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.
Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.
The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.
“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.
COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
Overcoming COVID
Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.
A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.
But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.
The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.
They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.
Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.
“Now we have modern technologies to do this more systematically.”
The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.
“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”
A version of this article first appeared on WebMD.com.
During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?
Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.
“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.
Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.
There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.
Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
A genetic quirk
In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.
The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.
The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.
Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.
Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.
Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
Locking out illness
“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”
Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.
Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.
The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.
“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
No norovirus
Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.
But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.
“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.
Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”
We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”
In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.
Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
Thwarting uberculosis
Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.
“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.
Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.
The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.
“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.
COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
Overcoming COVID
Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.
A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.
But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.
The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.
They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.
Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.
“Now we have modern technologies to do this more systematically.”
The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.
“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”
A version of this article first appeared on WebMD.com.
During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?
Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.
“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.
Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.
There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.
Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
A genetic quirk
In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.
The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.
The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.
Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.
Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.
Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
Locking out illness
“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”
Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.
Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.
The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.
“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
No norovirus
Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.
But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.
“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.
Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”
We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”
In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.
Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
Thwarting uberculosis
Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.
“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.
Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.
The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.
“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.
COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
Overcoming COVID
Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.
A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.
But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.
The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.
They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.
Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.
“Now we have modern technologies to do this more systematically.”
The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.
“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”
A version of this article first appeared on WebMD.com.
Comments & Controversies
A broken system
I was relieved to see your article “I have a dream … for psychiatry” (From the Editor,
Psychiatry does need better treatments. On the other hand, we do have many effective treatments that simply are not available to many.
This brings me to ask, how is it that overall psychiatric care is actually worse now than in, say, the late 20th century? There might have been fewer psychopharmacologic treatments available back then, but there was overall better access to care, and a largely intact system. For lower-functioning patients, such as those who are homeless or in jail, I do believe this is the case, as I will explain. But even higher-functioning private practice patients are affected by the shortage of psychiatrists.
In 2022, the system is broken. Funding is abysmal, and numerous psychiatric hospital closures across the United States have led to simply no reasonable local access for many.
Prisons and jails are the new treatment centers! As you have rightly pointed out, by being housed in prisons with violent criminals, severely mentally ill patients are subjected to physical and sexual abuse daily.
Laws meant to protect mentally ill individuals, such as psychiatric holds, are often not implemented. Severely mentally ill patients can meet the criteria to be categorized as a danger to self, danger to others, or gravely disabled, but can’t get crisis intervention. Abandoning these patients to the streets is, in part, fueling homelessness and drug addiction.
In my opinion, the broken system is the fundamental problem that needs to be solved. Although I long for novel treatments, if there were such breakthrough treatments available—as exciting as that may be—how could they be delivered effectively in our current broken system? In other words, how can these patients be treated with neuroscientific breakthrough treatments without the necessary psychiatric infrastructure? We are at such an extreme, I worry for our specialty.
In Karl Menninger’s The Crime of Punishment, one passage stuck with me: “I suspect that all the crimes committed by all the jailed criminals do not equal in total social damage that of the crimes committed against them.”1 I have often wondered how that relates to the criminalized mentally ill, who are punished daily by being in horrific, abusive, unsafe settings. What truly is their crime? Being mentally ill?
Given how the system is now engineered to throw these patients in prison and allow them to be abused instead of admitting them to a psychiatric hospital, one must wonder: How did this come to be? Could it go beyond stigma to actual hatred and contempt for these people? After all, as psychiatrists, the abuse is in plain sight.
Finally, I have often wondered why there has not been a robust psychiatric organizational response to the breakdown in access to patient care. I can only hope that one day there can be.
Dr. Nasrallah responds
Thank you for your comments on my editorial. I sense that you are quite frustrated with the current status of psychiatry, and are longing for improvements.
I do share some of your concerns about: 1) society turning a blind eye to the mentally ill (and I have written about that from the angle of tragically high suicide rate1); 2) the hatred and contempt embedded within stigma of serious mental disorders; 3) the deplorable criminalization and trans-institutionalization of our patients from state hospitals to jails and prisons; 4) the shortage of acute psychiatric beds in many communities because the wards were converted to highly lucrative, procedure-oriented programs; 5) the dysfunctional public mental health system; and 6) the need for new and novel treatments.
However, despite those challenges, I remain optimistic that the future of psychiatry is bright because I keep abreast of the stunning neuroscience advances every day that will be translated into psychiatric treatments in the future. I envision a time when these brain research breakthroughs will lead to important clinical applications, such as a better diagnostic system using biomarkers (precision psychiatry), not just a cluster of clinical symptoms, and to brave new therapeutic interventions with superior efficacy and better safety. I would not be surprised if psychiatry and neurology will again merge after decades of separation, and that will certainly erase much of the stigma of disorders of the mind, which is the virtual brain.
Please hang in there, and do not let your patients perceive a sense of resignation and pessimism about psychiatry. Both our patients and psychiatrists need to be uplifted by hope for a better future.
1. Menninger K. The Crime of Punishment. Viking Adult; 1968.
2. Nasrallah HA. The scourge of societal anosognosia about the mentally ill. Current Psychiatry. 2016;15(6):19,23-24.
A broken system
I was relieved to see your article “I have a dream … for psychiatry” (From the Editor,
Psychiatry does need better treatments. On the other hand, we do have many effective treatments that simply are not available to many.
This brings me to ask, how is it that overall psychiatric care is actually worse now than in, say, the late 20th century? There might have been fewer psychopharmacologic treatments available back then, but there was overall better access to care, and a largely intact system. For lower-functioning patients, such as those who are homeless or in jail, I do believe this is the case, as I will explain. But even higher-functioning private practice patients are affected by the shortage of psychiatrists.
In 2022, the system is broken. Funding is abysmal, and numerous psychiatric hospital closures across the United States have led to simply no reasonable local access for many.
Prisons and jails are the new treatment centers! As you have rightly pointed out, by being housed in prisons with violent criminals, severely mentally ill patients are subjected to physical and sexual abuse daily.
Laws meant to protect mentally ill individuals, such as psychiatric holds, are often not implemented. Severely mentally ill patients can meet the criteria to be categorized as a danger to self, danger to others, or gravely disabled, but can’t get crisis intervention. Abandoning these patients to the streets is, in part, fueling homelessness and drug addiction.
In my opinion, the broken system is the fundamental problem that needs to be solved. Although I long for novel treatments, if there were such breakthrough treatments available—as exciting as that may be—how could they be delivered effectively in our current broken system? In other words, how can these patients be treated with neuroscientific breakthrough treatments without the necessary psychiatric infrastructure? We are at such an extreme, I worry for our specialty.
In Karl Menninger’s The Crime of Punishment, one passage stuck with me: “I suspect that all the crimes committed by all the jailed criminals do not equal in total social damage that of the crimes committed against them.”1 I have often wondered how that relates to the criminalized mentally ill, who are punished daily by being in horrific, abusive, unsafe settings. What truly is their crime? Being mentally ill?
Given how the system is now engineered to throw these patients in prison and allow them to be abused instead of admitting them to a psychiatric hospital, one must wonder: How did this come to be? Could it go beyond stigma to actual hatred and contempt for these people? After all, as psychiatrists, the abuse is in plain sight.
Finally, I have often wondered why there has not been a robust psychiatric organizational response to the breakdown in access to patient care. I can only hope that one day there can be.
Dr. Nasrallah responds
Thank you for your comments on my editorial. I sense that you are quite frustrated with the current status of psychiatry, and are longing for improvements.
I do share some of your concerns about: 1) society turning a blind eye to the mentally ill (and I have written about that from the angle of tragically high suicide rate1); 2) the hatred and contempt embedded within stigma of serious mental disorders; 3) the deplorable criminalization and trans-institutionalization of our patients from state hospitals to jails and prisons; 4) the shortage of acute psychiatric beds in many communities because the wards were converted to highly lucrative, procedure-oriented programs; 5) the dysfunctional public mental health system; and 6) the need for new and novel treatments.
However, despite those challenges, I remain optimistic that the future of psychiatry is bright because I keep abreast of the stunning neuroscience advances every day that will be translated into psychiatric treatments in the future. I envision a time when these brain research breakthroughs will lead to important clinical applications, such as a better diagnostic system using biomarkers (precision psychiatry), not just a cluster of clinical symptoms, and to brave new therapeutic interventions with superior efficacy and better safety. I would not be surprised if psychiatry and neurology will again merge after decades of separation, and that will certainly erase much of the stigma of disorders of the mind, which is the virtual brain.
Please hang in there, and do not let your patients perceive a sense of resignation and pessimism about psychiatry. Both our patients and psychiatrists need to be uplifted by hope for a better future.
A broken system
I was relieved to see your article “I have a dream … for psychiatry” (From the Editor,
Psychiatry does need better treatments. On the other hand, we do have many effective treatments that simply are not available to many.
This brings me to ask, how is it that overall psychiatric care is actually worse now than in, say, the late 20th century? There might have been fewer psychopharmacologic treatments available back then, but there was overall better access to care, and a largely intact system. For lower-functioning patients, such as those who are homeless or in jail, I do believe this is the case, as I will explain. But even higher-functioning private practice patients are affected by the shortage of psychiatrists.
In 2022, the system is broken. Funding is abysmal, and numerous psychiatric hospital closures across the United States have led to simply no reasonable local access for many.
Prisons and jails are the new treatment centers! As you have rightly pointed out, by being housed in prisons with violent criminals, severely mentally ill patients are subjected to physical and sexual abuse daily.
Laws meant to protect mentally ill individuals, such as psychiatric holds, are often not implemented. Severely mentally ill patients can meet the criteria to be categorized as a danger to self, danger to others, or gravely disabled, but can’t get crisis intervention. Abandoning these patients to the streets is, in part, fueling homelessness and drug addiction.
In my opinion, the broken system is the fundamental problem that needs to be solved. Although I long for novel treatments, if there were such breakthrough treatments available—as exciting as that may be—how could they be delivered effectively in our current broken system? In other words, how can these patients be treated with neuroscientific breakthrough treatments without the necessary psychiatric infrastructure? We are at such an extreme, I worry for our specialty.
In Karl Menninger’s The Crime of Punishment, one passage stuck with me: “I suspect that all the crimes committed by all the jailed criminals do not equal in total social damage that of the crimes committed against them.”1 I have often wondered how that relates to the criminalized mentally ill, who are punished daily by being in horrific, abusive, unsafe settings. What truly is their crime? Being mentally ill?
Given how the system is now engineered to throw these patients in prison and allow them to be abused instead of admitting them to a psychiatric hospital, one must wonder: How did this come to be? Could it go beyond stigma to actual hatred and contempt for these people? After all, as psychiatrists, the abuse is in plain sight.
Finally, I have often wondered why there has not been a robust psychiatric organizational response to the breakdown in access to patient care. I can only hope that one day there can be.
Dr. Nasrallah responds
Thank you for your comments on my editorial. I sense that you are quite frustrated with the current status of psychiatry, and are longing for improvements.
I do share some of your concerns about: 1) society turning a blind eye to the mentally ill (and I have written about that from the angle of tragically high suicide rate1); 2) the hatred and contempt embedded within stigma of serious mental disorders; 3) the deplorable criminalization and trans-institutionalization of our patients from state hospitals to jails and prisons; 4) the shortage of acute psychiatric beds in many communities because the wards were converted to highly lucrative, procedure-oriented programs; 5) the dysfunctional public mental health system; and 6) the need for new and novel treatments.
However, despite those challenges, I remain optimistic that the future of psychiatry is bright because I keep abreast of the stunning neuroscience advances every day that will be translated into psychiatric treatments in the future. I envision a time when these brain research breakthroughs will lead to important clinical applications, such as a better diagnostic system using biomarkers (precision psychiatry), not just a cluster of clinical symptoms, and to brave new therapeutic interventions with superior efficacy and better safety. I would not be surprised if psychiatry and neurology will again merge after decades of separation, and that will certainly erase much of the stigma of disorders of the mind, which is the virtual brain.
Please hang in there, and do not let your patients perceive a sense of resignation and pessimism about psychiatry. Both our patients and psychiatrists need to be uplifted by hope for a better future.
1. Menninger K. The Crime of Punishment. Viking Adult; 1968.
2. Nasrallah HA. The scourge of societal anosognosia about the mentally ill. Current Psychiatry. 2016;15(6):19,23-24.
1. Menninger K. The Crime of Punishment. Viking Adult; 1968.
2. Nasrallah HA. The scourge of societal anosognosia about the mentally ill. Current Psychiatry. 2016;15(6):19,23-24.
‘Deaths of despair’ rising, but only in the U.S.
In the United States,
This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.
One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.
In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.
The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
U.S. is an outlier
From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.
However, much of modern life offers few opportunities for surprise and dopamine pulses.
“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.
The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.
The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.
Modern life is more isolating, often with hours spent alone in front of a computer screen.
Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.
So why has the United States suffered more deaths of despair?
Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.
This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.
By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.
However, they caution against the “medicalization” of every identified cause of rising death rates.
“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.
“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.
Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the United States,
This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.
One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.
In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.
The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
U.S. is an outlier
From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.
However, much of modern life offers few opportunities for surprise and dopamine pulses.
“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.
The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.
The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.
Modern life is more isolating, often with hours spent alone in front of a computer screen.
Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.
So why has the United States suffered more deaths of despair?
Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.
This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.
By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.
However, they caution against the “medicalization” of every identified cause of rising death rates.
“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.
“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.
Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the United States,
This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.
One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.
In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.
The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
U.S. is an outlier
From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.
However, much of modern life offers few opportunities for surprise and dopamine pulses.
“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.
The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.
The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.
Modern life is more isolating, often with hours spent alone in front of a computer screen.
Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.
So why has the United States suffered more deaths of despair?
Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.
This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.
By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.
However, they caution against the “medicalization” of every identified cause of rising death rates.
“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.
“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.
Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Infectious disease pop quiz: Clinical challenge #13 for the ObGyn
For a moderately ill pregnant woman, what is the most appropriate antibiotic combination for inpatient treatment of community-acquired pneumonia?
Continue to the answer...
This patient should be treated with intravenous ceftriaxone (2 g every 24 hours) plus oral or intravenous azithromycin. The appropriate oral dose of azithromycin is 500 mg on day 1, then 250 mg daily for 4 doses. The appropriate intravenous dose of azithromycin is 500 mg every 24 hours. The goal is to provide appropriate coverage for the most likely pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and mycoplasmas. (Antibacterial drugs for community-acquired pneumonia. Med Lett Drugs Ther. 2021:63:10-14. Postma DF, van Werkoven CH, van Eldin LJ, et al; CAP-START Study Group. Antibiotic treatment strategies for community acquired pneumonia in adults. N Engl J Med. 2015;372:1312-1323.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
For a moderately ill pregnant woman, what is the most appropriate antibiotic combination for inpatient treatment of community-acquired pneumonia?
Continue to the answer...
This patient should be treated with intravenous ceftriaxone (2 g every 24 hours) plus oral or intravenous azithromycin. The appropriate oral dose of azithromycin is 500 mg on day 1, then 250 mg daily for 4 doses. The appropriate intravenous dose of azithromycin is 500 mg every 24 hours. The goal is to provide appropriate coverage for the most likely pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and mycoplasmas. (Antibacterial drugs for community-acquired pneumonia. Med Lett Drugs Ther. 2021:63:10-14. Postma DF, van Werkoven CH, van Eldin LJ, et al; CAP-START Study Group. Antibiotic treatment strategies for community acquired pneumonia in adults. N Engl J Med. 2015;372:1312-1323.)
For a moderately ill pregnant woman, what is the most appropriate antibiotic combination for inpatient treatment of community-acquired pneumonia?
Continue to the answer...
This patient should be treated with intravenous ceftriaxone (2 g every 24 hours) plus oral or intravenous azithromycin. The appropriate oral dose of azithromycin is 500 mg on day 1, then 250 mg daily for 4 doses. The appropriate intravenous dose of azithromycin is 500 mg every 24 hours. The goal is to provide appropriate coverage for the most likely pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and mycoplasmas. (Antibacterial drugs for community-acquired pneumonia. Med Lett Drugs Ther. 2021:63:10-14. Postma DF, van Werkoven CH, van Eldin LJ, et al; CAP-START Study Group. Antibiotic treatment strategies for community acquired pneumonia in adults. N Engl J Med. 2015;372:1312-1323.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
“I didn’t want to meet you.” Dispelling myths about palliative care
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
Lipedema: A potentially devastating, often unrecognized disease
” according to C. William Hanke, MD, MPH.
“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.
“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”
Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.
Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”
One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
Lipedema stages, treatment
Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.
“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”
In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.
In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”
A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.
Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.
“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”
Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.
Dr. Hanke reported having no financial conflicts related to his presentation.
” according to C. William Hanke, MD, MPH.
“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.
“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”
Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.
Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”
One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
Lipedema stages, treatment
Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.
“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”
In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.
In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”
A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.
Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.
“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”
Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.
Dr. Hanke reported having no financial conflicts related to his presentation.
” according to C. William Hanke, MD, MPH.
“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.
“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”
Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.
Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”
One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
Lipedema stages, treatment
Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.
“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”
In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.
In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”
A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.
Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.
“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”
Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.
Dr. Hanke reported having no financial conflicts related to his presentation.
FROM ODAC 2022