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When CPI fails, HL patients should get timely allo-HCT
In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York.
“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”
To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.
Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).
“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)
At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor.
They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).
However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”
The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.
Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”
Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.
The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.
“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.”
However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York.
“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”
To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.
Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).
“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)
At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor.
They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).
However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”
The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.
Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”
Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.
The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.
“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.”
However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York.
“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”
To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.
Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).
“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)
At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor.
They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).
However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”
The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.
Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”
Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.
The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.
“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.”
However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
Long-term cannabis use linked to dementia risk factors
A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.
“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.
“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.
The study was recently published online in the American Journal of Psychiatry.
Growing use in Boomers
Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.
Others found no significant structural differences between the brains of cannabis users and nonusers.
An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.
Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.
To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.
The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.
Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier.
Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.
This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
Shrinking hippocampal volume
Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:
- Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
- Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
- Long-term tobacco users (n = 75)
- Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
- Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation
Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.
The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.
The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).
Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.
However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.
Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.
Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
More potent
“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.
The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.
“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.
Additionally, some group sizes were small, raising concerns about low statistical power.
“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.
“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.
The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.
“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.
A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.
The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
‘Fantastic’ research
Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”
“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.
“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.
On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.
Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.
“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.
“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.
The study was recently published online in the American Journal of Psychiatry.
Growing use in Boomers
Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.
Others found no significant structural differences between the brains of cannabis users and nonusers.
An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.
Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.
To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.
The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.
Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier.
Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.
This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
Shrinking hippocampal volume
Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:
- Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
- Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
- Long-term tobacco users (n = 75)
- Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
- Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation
Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.
The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.
The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).
Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.
However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.
Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.
Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
More potent
“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.
The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.
“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.
Additionally, some group sizes were small, raising concerns about low statistical power.
“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.
“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.
The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.
“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.
A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.
The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
‘Fantastic’ research
Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”
“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.
“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.
On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.
Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.
“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.
“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.
The study was recently published online in the American Journal of Psychiatry.
Growing use in Boomers
Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.
Others found no significant structural differences between the brains of cannabis users and nonusers.
An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.
Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.
To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.
The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.
Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier.
Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.
This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
Shrinking hippocampal volume
Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:
- Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
- Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
- Long-term tobacco users (n = 75)
- Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
- Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation
Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.
The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.
The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).
Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.
However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.
Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.
Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
More potent
“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.
The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.
“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.
Additionally, some group sizes were small, raising concerns about low statistical power.
“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.
“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.
The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.
“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.
A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.
The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
‘Fantastic’ research
Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”
“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.
“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.
On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.
Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
University of Washington, Harvard ranked top medical schools for second year
It may seem like déjà vu, as not much has changed regarding the rankings of top U.S. medical schools over the past 2 years.
The University of Washington, Seattle retained its ranking from the U.S. News & World Report as the top medical school for primary care for 2023. Also repeating its 2022 standing as the top medical school for research is Harvard University.
In the primary care ranking, the top 10 schools after the University of Washington were the University of California, San Francisco; the University of Minnesota; Oregon Health and Science University; the University of North Carolina at Chapel Hill; the University of Colorado; the University of Nebraska Medical Center; the University of California, Davis; and Harvard. Three schools tied for the no. 10 slot: the University of Kansas Medical Center, the University of Massachusetts Chan Medical Center, and the University of Pittsburgh.
The top five schools with the most graduates practicing in primary care specialties are Des Moines University, Iowa (50.6%); the University of Pikeville (Ky.) (46.8%); Western University of Health Sciences, Pomona, California (46%); William Carey University College of Osteopathic Medicine, Hattiesburg, Mississippi (44.7%); and A.T. Still University of Health Sciences, Kirksville, Missouri (44.3%).
Best for research
When it comes to schools ranking the highest for research, the Grossman School of Medicine at New York University takes the no. 2 spot after Harvard. Three schools were tied for the no. 3 spot: Columbia University, Johns Hopkins University, and the University of California, San Francisco; and two schools for no. 6: Duke University and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. No. 8 goes to Stanford University, followed by the University of Washington. Rounding out the top 10 is Yale University.
Specialty ranks
The top-ranked schools in eight specialties are as follows:
- Anesthesiology: Harvard
- Family medicine: the University of Washington
- Internal medicine: Johns Hopkins
- Obstetrics/gynecology: Harvard
- Pediatrics: the University of Pennsylvania (Perelman)
- Psychiatry: Harvard
- Radiology: Johns Hopkins
- Surgery: Harvard
Most diverse student body
If you’re looking for a school with significant minority representation, Howard University, Washington, D.C., ranked highest (76.8%), followed by the Wertheim College of Medicine at Florida International University, Miami (43.2%). The University of California, Davis (40%), Sacramento, California, and the University of Vermont (Larner), Burlington (14.1%), tied for third.
Three southern schools take top honors for the most graduates practicing in underserved areas, starting with the University of South Carolina (70.9%), followed by the University of Mississippi (66.2%), and East Tennessee State University (Quillen), Johnson City, Tennessee (65.8%).
The colleges with the most graduates practicing in rural areas are William Carey University College of Osteopathic Medicine (28%), the University of Pikesville (25.6%), and the University of Mississippi (22.1%).
College debt
The medical school where graduates have the most debt is Nova Southeastern University Patel College of Osteopathic Medicine, Fort Lauderdale, Florida. Graduates incurred an average debt of $309,206. Western University of Health Sciences graduates racked up $276,840 in debt, followed by graduates of West Virginia School of Osteopathic Medicine, owing $268,416.
Ranking criteria
Each year, U.S. News ranks hundreds of U.S. colleges and universities. Medical schools fall under the rankings for best graduate schools.
U.S. News surveyed 192 medical and osteopathic schools accredited in 2021 by the Liaison Committee on Medical Education or the American Osteopathic Association. Among the schools surveyed in fall 2021 and early 2022, 130 schools responded. Of those, 124 were included in both the research and primary care rankings.
The criteria for ranking include faculty resources, academic achievements of entering students, and qualitative assessments by schools and residency directors.
A version of this article first appeared on Medscape.com.
It may seem like déjà vu, as not much has changed regarding the rankings of top U.S. medical schools over the past 2 years.
The University of Washington, Seattle retained its ranking from the U.S. News & World Report as the top medical school for primary care for 2023. Also repeating its 2022 standing as the top medical school for research is Harvard University.
In the primary care ranking, the top 10 schools after the University of Washington were the University of California, San Francisco; the University of Minnesota; Oregon Health and Science University; the University of North Carolina at Chapel Hill; the University of Colorado; the University of Nebraska Medical Center; the University of California, Davis; and Harvard. Three schools tied for the no. 10 slot: the University of Kansas Medical Center, the University of Massachusetts Chan Medical Center, and the University of Pittsburgh.
The top five schools with the most graduates practicing in primary care specialties are Des Moines University, Iowa (50.6%); the University of Pikeville (Ky.) (46.8%); Western University of Health Sciences, Pomona, California (46%); William Carey University College of Osteopathic Medicine, Hattiesburg, Mississippi (44.7%); and A.T. Still University of Health Sciences, Kirksville, Missouri (44.3%).
Best for research
When it comes to schools ranking the highest for research, the Grossman School of Medicine at New York University takes the no. 2 spot after Harvard. Three schools were tied for the no. 3 spot: Columbia University, Johns Hopkins University, and the University of California, San Francisco; and two schools for no. 6: Duke University and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. No. 8 goes to Stanford University, followed by the University of Washington. Rounding out the top 10 is Yale University.
Specialty ranks
The top-ranked schools in eight specialties are as follows:
- Anesthesiology: Harvard
- Family medicine: the University of Washington
- Internal medicine: Johns Hopkins
- Obstetrics/gynecology: Harvard
- Pediatrics: the University of Pennsylvania (Perelman)
- Psychiatry: Harvard
- Radiology: Johns Hopkins
- Surgery: Harvard
Most diverse student body
If you’re looking for a school with significant minority representation, Howard University, Washington, D.C., ranked highest (76.8%), followed by the Wertheim College of Medicine at Florida International University, Miami (43.2%). The University of California, Davis (40%), Sacramento, California, and the University of Vermont (Larner), Burlington (14.1%), tied for third.
Three southern schools take top honors for the most graduates practicing in underserved areas, starting with the University of South Carolina (70.9%), followed by the University of Mississippi (66.2%), and East Tennessee State University (Quillen), Johnson City, Tennessee (65.8%).
The colleges with the most graduates practicing in rural areas are William Carey University College of Osteopathic Medicine (28%), the University of Pikesville (25.6%), and the University of Mississippi (22.1%).
College debt
The medical school where graduates have the most debt is Nova Southeastern University Patel College of Osteopathic Medicine, Fort Lauderdale, Florida. Graduates incurred an average debt of $309,206. Western University of Health Sciences graduates racked up $276,840 in debt, followed by graduates of West Virginia School of Osteopathic Medicine, owing $268,416.
Ranking criteria
Each year, U.S. News ranks hundreds of U.S. colleges and universities. Medical schools fall under the rankings for best graduate schools.
U.S. News surveyed 192 medical and osteopathic schools accredited in 2021 by the Liaison Committee on Medical Education or the American Osteopathic Association. Among the schools surveyed in fall 2021 and early 2022, 130 schools responded. Of those, 124 were included in both the research and primary care rankings.
The criteria for ranking include faculty resources, academic achievements of entering students, and qualitative assessments by schools and residency directors.
A version of this article first appeared on Medscape.com.
It may seem like déjà vu, as not much has changed regarding the rankings of top U.S. medical schools over the past 2 years.
The University of Washington, Seattle retained its ranking from the U.S. News & World Report as the top medical school for primary care for 2023. Also repeating its 2022 standing as the top medical school for research is Harvard University.
In the primary care ranking, the top 10 schools after the University of Washington were the University of California, San Francisco; the University of Minnesota; Oregon Health and Science University; the University of North Carolina at Chapel Hill; the University of Colorado; the University of Nebraska Medical Center; the University of California, Davis; and Harvard. Three schools tied for the no. 10 slot: the University of Kansas Medical Center, the University of Massachusetts Chan Medical Center, and the University of Pittsburgh.
The top five schools with the most graduates practicing in primary care specialties are Des Moines University, Iowa (50.6%); the University of Pikeville (Ky.) (46.8%); Western University of Health Sciences, Pomona, California (46%); William Carey University College of Osteopathic Medicine, Hattiesburg, Mississippi (44.7%); and A.T. Still University of Health Sciences, Kirksville, Missouri (44.3%).
Best for research
When it comes to schools ranking the highest for research, the Grossman School of Medicine at New York University takes the no. 2 spot after Harvard. Three schools were tied for the no. 3 spot: Columbia University, Johns Hopkins University, and the University of California, San Francisco; and two schools for no. 6: Duke University and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. No. 8 goes to Stanford University, followed by the University of Washington. Rounding out the top 10 is Yale University.
Specialty ranks
The top-ranked schools in eight specialties are as follows:
- Anesthesiology: Harvard
- Family medicine: the University of Washington
- Internal medicine: Johns Hopkins
- Obstetrics/gynecology: Harvard
- Pediatrics: the University of Pennsylvania (Perelman)
- Psychiatry: Harvard
- Radiology: Johns Hopkins
- Surgery: Harvard
Most diverse student body
If you’re looking for a school with significant minority representation, Howard University, Washington, D.C., ranked highest (76.8%), followed by the Wertheim College of Medicine at Florida International University, Miami (43.2%). The University of California, Davis (40%), Sacramento, California, and the University of Vermont (Larner), Burlington (14.1%), tied for third.
Three southern schools take top honors for the most graduates practicing in underserved areas, starting with the University of South Carolina (70.9%), followed by the University of Mississippi (66.2%), and East Tennessee State University (Quillen), Johnson City, Tennessee (65.8%).
The colleges with the most graduates practicing in rural areas are William Carey University College of Osteopathic Medicine (28%), the University of Pikesville (25.6%), and the University of Mississippi (22.1%).
College debt
The medical school where graduates have the most debt is Nova Southeastern University Patel College of Osteopathic Medicine, Fort Lauderdale, Florida. Graduates incurred an average debt of $309,206. Western University of Health Sciences graduates racked up $276,840 in debt, followed by graduates of West Virginia School of Osteopathic Medicine, owing $268,416.
Ranking criteria
Each year, U.S. News ranks hundreds of U.S. colleges and universities. Medical schools fall under the rankings for best graduate schools.
U.S. News surveyed 192 medical and osteopathic schools accredited in 2021 by the Liaison Committee on Medical Education or the American Osteopathic Association. Among the schools surveyed in fall 2021 and early 2022, 130 schools responded. Of those, 124 were included in both the research and primary care rankings.
The criteria for ranking include faculty resources, academic achievements of entering students, and qualitative assessments by schools and residency directors.
A version of this article first appeared on Medscape.com.
Survivor’s story foreshadows one of oncology’s greatest successes
At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.
Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.
Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.
Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.
“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.
Transplantation for Hodgkin: The early 90s
Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.
When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”
However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.
It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.
In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
Mr. Unger’s experience, 30 years ago
According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).
“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”
Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”
The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.
After discussing the situation with his father, Mr. Unger decided to undergo the transplant.
The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”
Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.
“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”
The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.
However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”
“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
Treatment for Hodgkin lymphoma: 2022
For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.
Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”
Another key change, Dr. Perales said, is in the up-front management of the disease.
For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.
“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.
Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.
Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.
Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)
Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.
In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.
Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.
In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.
As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.
The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.
Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.
Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
The future: No chemo, no transplants?
“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.
What else remains to be done in the world of transplants for Hodgkin lymphoma?
Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”
The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.
Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.
Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.
Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.
“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.
Transplantation for Hodgkin: The early 90s
Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.
When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”
However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.
It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.
In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
Mr. Unger’s experience, 30 years ago
According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).
“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”
Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”
The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.
After discussing the situation with his father, Mr. Unger decided to undergo the transplant.
The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”
Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.
“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”
The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.
However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”
“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
Treatment for Hodgkin lymphoma: 2022
For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.
Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”
Another key change, Dr. Perales said, is in the up-front management of the disease.
For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.
“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.
Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.
Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.
Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)
Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.
In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.
Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.
In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.
As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.
The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.
Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.
Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
The future: No chemo, no transplants?
“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.
What else remains to be done in the world of transplants for Hodgkin lymphoma?
Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”
The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.
Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.
Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.
Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.
“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.
Transplantation for Hodgkin: The early 90s
Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.
When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”
However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.
It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.
In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
Mr. Unger’s experience, 30 years ago
According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).
“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”
Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”
The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.
After discussing the situation with his father, Mr. Unger decided to undergo the transplant.
The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”
Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.
“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”
The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.
However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”
“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
Treatment for Hodgkin lymphoma: 2022
For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.
Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”
Another key change, Dr. Perales said, is in the up-front management of the disease.
For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.
“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.
Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.
Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.
Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)
Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.
In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.
Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.
In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.
As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.
The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.
Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.
Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
The future: No chemo, no transplants?
“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.
What else remains to be done in the world of transplants for Hodgkin lymphoma?
Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”
The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”
Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
COVID-19 cardiovascular complications in children: AHA statement
Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.
However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.
The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.
It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.
On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.
The scientific statement was published online on in Circulation.
“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.
Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.
In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.
Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.
In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.
Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.
In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.
But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
MIS-C: Rare but severe
The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.
In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.
As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.
Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.
However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.
Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.
The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.
The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.
Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
COVID-19 vaccination
The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.
On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.
For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.
But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.
The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.
“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”
A version of this article first appeared on Medscape.com.
Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.
However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.
The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.
It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.
On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.
The scientific statement was published online on in Circulation.
“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.
Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.
In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.
Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.
In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.
Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.
In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.
But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
MIS-C: Rare but severe
The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.
In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.
As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.
Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.
However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.
Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.
The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.
The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.
Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
COVID-19 vaccination
The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.
On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.
For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.
But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.
The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.
“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”
A version of this article first appeared on Medscape.com.
Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.
However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.
The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.
It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.
On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.
The scientific statement was published online on in Circulation.
“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.
Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.
In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.
Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.
In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.
Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.
In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.
But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
MIS-C: Rare but severe
The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.
In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.
As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.
Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.
However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.
Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.
The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.
The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.
Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
COVID-19 vaccination
The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.
On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.
For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.
But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.
The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.
“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Statins tied to lower risk for parkinsonism
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Study finds discrepancies in biopsy decisions, diagnoses based on skin type
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Some leukemias detectable up to 16 years before diagnosis?
Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”
“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.
Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.
Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.
This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.
“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”
Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.
“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.
The investigators also found that:
- Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
- High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
- The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
- No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.
“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.
The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”
The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”
“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.
In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .
They also raise new questions and point to new directions for research, Dr. Marti noted.
“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”
The study authors and Dr. Marti reported having no competing financial interests.
Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”
“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.
Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.
Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.
This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.
“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”
Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.
“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.
The investigators also found that:
- Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
- High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
- The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
- No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.
“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.
The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”
The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”
“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.
In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .
They also raise new questions and point to new directions for research, Dr. Marti noted.
“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”
The study authors and Dr. Marti reported having no competing financial interests.
Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”
“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.
Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.
Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.
This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.
“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”
Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.
“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.
The investigators also found that:
- Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
- High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
- The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
- No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.
“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.
The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”
The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”
“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.
In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .
They also raise new questions and point to new directions for research, Dr. Marti noted.
“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”
The study authors and Dr. Marti reported having no competing financial interests.
FROM BLOOD
Preterm C-sections, induced deliveries dropped during COVID-19 pandemic
Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.
Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.
The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.
The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.
That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.
Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”
Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.
So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.
To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.
If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.
Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.
“It’s always a good question for health care,” she said, “are we doing more than we need to?”
Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.
“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”
The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.
“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”
The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.
“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.
The study authors and Dr. Zapata reported no relevant financial relationships.
Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.
Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.
The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.
The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.
That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.
Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”
Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.
So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.
To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.
If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.
Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.
“It’s always a good question for health care,” she said, “are we doing more than we need to?”
Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.
“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”
The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.
“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”
The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.
“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.
The study authors and Dr. Zapata reported no relevant financial relationships.
Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.
Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.
The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.
The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.
That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.
Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”
Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.
So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.
To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.
If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.
Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.
“It’s always a good question for health care,” she said, “are we doing more than we need to?”
Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.
“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”
The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.
“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”
The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.
“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.
The study authors and Dr. Zapata reported no relevant financial relationships.
FROM PEDIATRICS
‘Eye-opening’ experience on the other side of the hospital bed
The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.
“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.
Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.
But she was propelled into quite a different role when her mother was admitted to the hospital.
Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.
“She needed someone to translate what was going on because she didn’t feel well,” she added.
Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”
Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”
“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.
Her thread has since garnered thousands of “likes” and scores of comments and retweets.
She began the Twitter thread explaining what prompted her comments:
“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”
“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’
2. End your patient visit with a summary of the plan for the day.
3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.
4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).
5. Many older [patients] get confused in the hospital. Repetition is a good thing.
6. Speak to a family member at least once per day to relay the plan.
7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’
8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).
9. When possible, sit at eye level with your patient (I love these stools from @YNHH).
10. Take time to listen.”
Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”
Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”
Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.
“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.
Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”
@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”
Patients also shared experiences and offered suggestions.
“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”
Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”
Dr. Kunz said she was taken aback but pleased by the response to her Tweet.
“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”
Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.
“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”
In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.
A version of this article first appeared on Medscape.com.
The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.
“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.
Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.
But she was propelled into quite a different role when her mother was admitted to the hospital.
Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.
“She needed someone to translate what was going on because she didn’t feel well,” she added.
Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”
Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”
“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.
Her thread has since garnered thousands of “likes” and scores of comments and retweets.
She began the Twitter thread explaining what prompted her comments:
“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”
“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’
2. End your patient visit with a summary of the plan for the day.
3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.
4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).
5. Many older [patients] get confused in the hospital. Repetition is a good thing.
6. Speak to a family member at least once per day to relay the plan.
7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’
8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).
9. When possible, sit at eye level with your patient (I love these stools from @YNHH).
10. Take time to listen.”
Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”
Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”
Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.
“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.
Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”
@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”
Patients also shared experiences and offered suggestions.
“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”
Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”
Dr. Kunz said she was taken aback but pleased by the response to her Tweet.
“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”
Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.
“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”
In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.
A version of this article first appeared on Medscape.com.
The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.
“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.
Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.
But she was propelled into quite a different role when her mother was admitted to the hospital.
Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.
“She needed someone to translate what was going on because she didn’t feel well,” she added.
Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”
Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”
“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.
Her thread has since garnered thousands of “likes” and scores of comments and retweets.
She began the Twitter thread explaining what prompted her comments:
“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”
“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’
2. End your patient visit with a summary of the plan for the day.
3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.
4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).
5. Many older [patients] get confused in the hospital. Repetition is a good thing.
6. Speak to a family member at least once per day to relay the plan.
7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’
8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).
9. When possible, sit at eye level with your patient (I love these stools from @YNHH).
10. Take time to listen.”
Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”
Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”
Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.
“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.
Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”
@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”
Patients also shared experiences and offered suggestions.
“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”
Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”
Dr. Kunz said she was taken aback but pleased by the response to her Tweet.
“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”
Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.
“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”
In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.
A version of this article first appeared on Medscape.com.