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'Paradigm shift’: Luspatercept for MDS
“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.
“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.
Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.
“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.
“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.
In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.
Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.
While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.
Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.
In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.
To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.
For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.
Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.
For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).
In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).
Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.
Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).
The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.
In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.
Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).
“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.
Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”
“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.
Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.
“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”
“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.
“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.
The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.
“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.
“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.
Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.
“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.
“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.
In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.
Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.
While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.
Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.
In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.
To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.
For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.
Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.
For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).
In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).
Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.
Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).
The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.
In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.
Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).
“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.
Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”
“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.
Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.
“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”
“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.
“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.
The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.
“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.
“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.
Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.
“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.
“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.
In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.
Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.
While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.
Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.
In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.
To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.
For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.
Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.
For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).
In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).
Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.
Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).
The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.
In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.
Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).
“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.
Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”
“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.
Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.
“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”
“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.
“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.
The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.
FROM ASCO 2023
People still want their medical intelligence in human form
Doctors or AI? Lukewarm vote of confidence goes to …
Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.
And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.
They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?
And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.
How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
Explaining the joke makes it funnier, right?
Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”
This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.
Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.
In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.
During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.
The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
Hot take: Humans aren’t that special
We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.
Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.
This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.
“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.
The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.
Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.
So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.
Doctors or AI? Lukewarm vote of confidence goes to …
Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.
And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.
They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?
And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.
How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
Explaining the joke makes it funnier, right?
Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”
This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.
Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.
In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.
During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.
The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
Hot take: Humans aren’t that special
We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.
Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.
This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.
“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.
The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.
Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.
So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.
Doctors or AI? Lukewarm vote of confidence goes to …
Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.
And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.
They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?
And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.
How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
Explaining the joke makes it funnier, right?
Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”
This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.
Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.
In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.
During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.
The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
Hot take: Humans aren’t that special
We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.
Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.
This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.
“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.
The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.
Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.
So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.
FDA approves new indication for avapritinib
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Focus of new ASH VTE guidelines: Thrombophilia testing
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
FROM BLOOD ADVANCES
Venetoclax boosts ibrutinib in high-risk CLL
Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.
By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”
According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”
The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.
Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.
For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.
An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.
At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.
It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”
The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”
The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.
In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”
She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”
Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”
AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.
Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.
By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”
According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”
The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.
Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.
For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.
An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.
At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.
It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”
The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”
The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.
In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”
She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”
Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”
AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.
Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.
By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”
According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”
The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.
Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.
For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.
An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.
At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.
It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”
The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”
The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.
In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”
She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”
Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”
AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.
FROM LEUKEMIA
FDA approves epcoritamab for r/r DLBCL
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
Morning PT
Tuesdays and Fridays are tough. Not so much because of clinic, but rather because of the 32 minutes before clinic that I’m on the Peloton bike. They are the mornings I dedicate to training VO2max.
Training VO2max, or maximal oxygen consumption, is simple. Spin for a leisurely, easy-breathing, 4 minutes, then for 4 minutes push yourself until you see the light of heaven and wish for death to come. Then relax for 4 minutes again. Repeat this cycle four to six times. Done justly, you will dread Tuesdays and Fridays too. The punishing cycle of a 4-minute push, then 4-minute recovery is, however, an excellent way to improve cardiovascular fitness. And no, I’m not training for the Boston Marathon, so why am I working so hard? Because I’m training for marathon clinic days for the next 20 years.
Now more than ever, I feel we have to be physically fit to deal with a physicians’ day’s work. It’s exhausting. The root cause is too much work, yes, but I believe being physically fit could help.
I was talking to an 86-year-old patient about this very topic recently. He was short, with a well-manicured goatee and shiny head. He stuck his arm out to shake my hand. “Glad we’re back to handshakes again, doc.” His grip was that of a 30-year-old. “Buff” you’d likely describe him: He is noticeably muscular, not a skinny old man. He’s an old Navy Master Chief who started a business in wholesale flowers, which distributes all over the United States. And he’s still working full time. Impressed, I asked his secret for such vigor. PT, he replied.
PT, or physical training, is a foundational element of the Navy. Every sailor starts his or her day with morning PT before carrying out their duties. Some 30 years later, this guy is still getting after it. He does push-ups, sit-ups, and pull-ups nearly every morning. Morning PT is what he attributes to his success not only in health, but also business. As he sees it, he has the business savvy and experience of an old guy and the energy and stamina of a college kid. A good combination for a successful life.
I’ve always been pretty fit. Lately, I’ve been trying to take it to the next level, to not just be “physically active,” but rather “high-performance fit.” There are plenty of sources for instruction; how to stay young and healthy isn’t a new idea after all. I mean, Herodotus wrote of finding the Fountain of Youth in the 5th century BCE. A couple thousand years later, it’s still on trend. One of my favorite sages giving health span advice is Peter Attia, MD. I’ve been a fan since I met him at TEDMED in 2013 and I marvel at the astounding body of work he has created since. A Johns Hopkins–trained surgeon, he has spent his career reviewing the scientific literature about longevity and sharing it as actionable content. His book, “Outlive: The Science and Art of Longevity” (New York: Penguin Random House, 2023) is a nice summary of his work. I recommend it.
Right now I’m switching between type 2 muscle fiber work (lots of jumping like my 2-year-old) and cardiovascular training including the aforementioned VO2max work. I cannot say that my patient inbox is any cleaner, or that I’m faster in the office, but I’m not flagging by the end of the day anymore. Master Chief challenged me to match his 10 pull-ups before he returns for his follow up visit. I’ll gladly give up Peloton sprints to work on that.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Tuesdays and Fridays are tough. Not so much because of clinic, but rather because of the 32 minutes before clinic that I’m on the Peloton bike. They are the mornings I dedicate to training VO2max.
Training VO2max, or maximal oxygen consumption, is simple. Spin for a leisurely, easy-breathing, 4 minutes, then for 4 minutes push yourself until you see the light of heaven and wish for death to come. Then relax for 4 minutes again. Repeat this cycle four to six times. Done justly, you will dread Tuesdays and Fridays too. The punishing cycle of a 4-minute push, then 4-minute recovery is, however, an excellent way to improve cardiovascular fitness. And no, I’m not training for the Boston Marathon, so why am I working so hard? Because I’m training for marathon clinic days for the next 20 years.
Now more than ever, I feel we have to be physically fit to deal with a physicians’ day’s work. It’s exhausting. The root cause is too much work, yes, but I believe being physically fit could help.
I was talking to an 86-year-old patient about this very topic recently. He was short, with a well-manicured goatee and shiny head. He stuck his arm out to shake my hand. “Glad we’re back to handshakes again, doc.” His grip was that of a 30-year-old. “Buff” you’d likely describe him: He is noticeably muscular, not a skinny old man. He’s an old Navy Master Chief who started a business in wholesale flowers, which distributes all over the United States. And he’s still working full time. Impressed, I asked his secret for such vigor. PT, he replied.
PT, or physical training, is a foundational element of the Navy. Every sailor starts his or her day with morning PT before carrying out their duties. Some 30 years later, this guy is still getting after it. He does push-ups, sit-ups, and pull-ups nearly every morning. Morning PT is what he attributes to his success not only in health, but also business. As he sees it, he has the business savvy and experience of an old guy and the energy and stamina of a college kid. A good combination for a successful life.
I’ve always been pretty fit. Lately, I’ve been trying to take it to the next level, to not just be “physically active,” but rather “high-performance fit.” There are plenty of sources for instruction; how to stay young and healthy isn’t a new idea after all. I mean, Herodotus wrote of finding the Fountain of Youth in the 5th century BCE. A couple thousand years later, it’s still on trend. One of my favorite sages giving health span advice is Peter Attia, MD. I’ve been a fan since I met him at TEDMED in 2013 and I marvel at the astounding body of work he has created since. A Johns Hopkins–trained surgeon, he has spent his career reviewing the scientific literature about longevity and sharing it as actionable content. His book, “Outlive: The Science and Art of Longevity” (New York: Penguin Random House, 2023) is a nice summary of his work. I recommend it.
Right now I’m switching between type 2 muscle fiber work (lots of jumping like my 2-year-old) and cardiovascular training including the aforementioned VO2max work. I cannot say that my patient inbox is any cleaner, or that I’m faster in the office, but I’m not flagging by the end of the day anymore. Master Chief challenged me to match his 10 pull-ups before he returns for his follow up visit. I’ll gladly give up Peloton sprints to work on that.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Tuesdays and Fridays are tough. Not so much because of clinic, but rather because of the 32 minutes before clinic that I’m on the Peloton bike. They are the mornings I dedicate to training VO2max.
Training VO2max, or maximal oxygen consumption, is simple. Spin for a leisurely, easy-breathing, 4 minutes, then for 4 minutes push yourself until you see the light of heaven and wish for death to come. Then relax for 4 minutes again. Repeat this cycle four to six times. Done justly, you will dread Tuesdays and Fridays too. The punishing cycle of a 4-minute push, then 4-minute recovery is, however, an excellent way to improve cardiovascular fitness. And no, I’m not training for the Boston Marathon, so why am I working so hard? Because I’m training for marathon clinic days for the next 20 years.
Now more than ever, I feel we have to be physically fit to deal with a physicians’ day’s work. It’s exhausting. The root cause is too much work, yes, but I believe being physically fit could help.
I was talking to an 86-year-old patient about this very topic recently. He was short, with a well-manicured goatee and shiny head. He stuck his arm out to shake my hand. “Glad we’re back to handshakes again, doc.” His grip was that of a 30-year-old. “Buff” you’d likely describe him: He is noticeably muscular, not a skinny old man. He’s an old Navy Master Chief who started a business in wholesale flowers, which distributes all over the United States. And he’s still working full time. Impressed, I asked his secret for such vigor. PT, he replied.
PT, or physical training, is a foundational element of the Navy. Every sailor starts his or her day with morning PT before carrying out their duties. Some 30 years later, this guy is still getting after it. He does push-ups, sit-ups, and pull-ups nearly every morning. Morning PT is what he attributes to his success not only in health, but also business. As he sees it, he has the business savvy and experience of an old guy and the energy and stamina of a college kid. A good combination for a successful life.
I’ve always been pretty fit. Lately, I’ve been trying to take it to the next level, to not just be “physically active,” but rather “high-performance fit.” There are plenty of sources for instruction; how to stay young and healthy isn’t a new idea after all. I mean, Herodotus wrote of finding the Fountain of Youth in the 5th century BCE. A couple thousand years later, it’s still on trend. One of my favorite sages giving health span advice is Peter Attia, MD. I’ve been a fan since I met him at TEDMED in 2013 and I marvel at the astounding body of work he has created since. A Johns Hopkins–trained surgeon, he has spent his career reviewing the scientific literature about longevity and sharing it as actionable content. His book, “Outlive: The Science and Art of Longevity” (New York: Penguin Random House, 2023) is a nice summary of his work. I recommend it.
Right now I’m switching between type 2 muscle fiber work (lots of jumping like my 2-year-old) and cardiovascular training including the aforementioned VO2max work. I cannot say that my patient inbox is any cleaner, or that I’m faster in the office, but I’m not flagging by the end of the day anymore. Master Chief challenged me to match his 10 pull-ups before he returns for his follow up visit. I’ll gladly give up Peloton sprints to work on that.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Review supports continued mask-wearing in health care visits
A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.
Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.
The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.
Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.
“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.
Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.
The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.
The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.
A version of this article first appeared on WebMD.com.
A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.
Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.
The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.
Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.
“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.
Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.
The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.
The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.
A version of this article first appeared on WebMD.com.
A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.
Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.
The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.
Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.
“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.
Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.
The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.
The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.
A version of this article first appeared on WebMD.com.
FROM ANNALS OF INTERNAL MEDICINE
COVID emergency over, but hundreds are still dying weekly
Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren.
Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.
Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.
“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.”
Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.
The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members.
It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.
“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”
The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.
“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
Historic drop in life expectancy
More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.
What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.
“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”
By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century.
Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.
As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
What is an acceptable threshold of death?
In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID.
The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.
“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said.
Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J., home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.
“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”
At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.
“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.”
One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”
Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.
What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks.
“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”
Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.
“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”
A version of this article first appeared on WebMD.com.
Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren.
Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.
Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.
“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.”
Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.
The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members.
It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.
“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”
The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.
“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
Historic drop in life expectancy
More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.
What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.
“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”
By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century.
Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.
As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
What is an acceptable threshold of death?
In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID.
The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.
“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said.
Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J., home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.
“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”
At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.
“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.”
One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”
Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.
What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks.
“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”
Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.
“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”
A version of this article first appeared on WebMD.com.
Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren.
Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.
Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.
“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.”
Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.
The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members.
It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.
“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”
The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.
“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
Historic drop in life expectancy
More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.
What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.
“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”
By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century.
Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.
As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
What is an acceptable threshold of death?
In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID.
The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.
“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said.
Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J., home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.
“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”
At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.
“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.”
One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”
Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.
What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks.
“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”
Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.
“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”
A version of this article first appeared on WebMD.com.
The antimicrobial peptide that even Pharma can love
Fastest peptide north, south, east, aaaaand west of the Pecos
Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.
Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.
Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.
The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.
The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
Speed healing: The wavy wound gets the swirl
Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?
You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.
They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.
The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.
Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.
The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.
As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
A little Jekyll, a little Hyde, and a little shop of horrors
More “Little Shop of Horrors” references are coming, so be prepared.
We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.
No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.
T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.
A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”
Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.
Fastest peptide north, south, east, aaaaand west of the Pecos
Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.
Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.
Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.
The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.
The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
Speed healing: The wavy wound gets the swirl
Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?
You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.
They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.
The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.
Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.
The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.
As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
A little Jekyll, a little Hyde, and a little shop of horrors
More “Little Shop of Horrors” references are coming, so be prepared.
We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.
No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.
T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.
A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”
Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.
Fastest peptide north, south, east, aaaaand west of the Pecos
Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.
Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.
Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.
The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.
The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
Speed healing: The wavy wound gets the swirl
Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?
You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.
They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.
The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.
Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.
The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.
As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
A little Jekyll, a little Hyde, and a little shop of horrors
More “Little Shop of Horrors” references are coming, so be prepared.
We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.
No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.
T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.
A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”
Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.