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Hip fracture patients with dementia benefit from increased rehab intensity
according to a recent Japanese study in the Archives of Physical Medicine and Rehabilitation.
Looking at 43,506 patients cared for at 1,053 hospitals, Kazuaki Uda, MPH, and colleagues of the University of Tokyo found that scores on the Barthel Index, a measure of functional status, climbed significantly as the frequency and duration of postoperative rehabilitation increased. There was also a statistically significant, but small, association with improved functional status and early initiation of rehabilitation.
“Our results suggest that additional days of rehabilitation or an additional 20 minutes for each daily rehabilitation session in acute-care hospitals may provide better functional outcomes for patients with dementia,” concluded Mr. Uda and coinvestigators.
The Barthel Index (BI) measures independence in performing 10 activities of daily living (ADLs), including feeding, bathing, grooming, and dressing; bowel, bladder, and toileting; and transfers, mobility, and stair use. Each ADL is rate 0, 5, 10, or, for some, 15 points, and higher scores indicate more independence.
Compared with patients who received 3 days or fewer of rehabilitation weekly, patients receiving 3-4 days of rehabilitation saw an improvement of 2.62 on the BI. For those receiving 4-5 days, 5-6 days, and 6 or more days of rehabilitation, BI scores were higher by 5.83, 7.56, and 9.16, respectively. The results were statistically significant for all but the 3-4 day rehabilitation group.
Similarly, patients who received longer periods of rehabilitation saw more improvement in functional status. Compared with those who received 20-39 minutes per day of rehabilitation, those who received 40-59 minutes of therapy saw an increase of 4.37 on the BI, and those receiving an hour or more of therapy saw BI scores rise by 6.60 – both significant increases.
These results included a multivariable analysis that accounted for a number of patient characteristics such as comorbidities and body mass index, as well as fracture, fixation, and anesthesia type, and the interval from injury to surgery.
Representing the data in another way, the investigators found that “each increase in the average units of rehabilitation (units per day) was associated with a 5.46 increase in the BI.”
This retrospective cohort study, when placed in the context of previous work, suggests that “patients with cognitive impairment may benefit from rehabilitation for functional gains after hip fracture surgery in both acute and postacute settings,” the investigators wrote. They noted, however, that patients with dementia have often been excluded from larger outcome studies of hip fracture rehabilitation.
Patients in this study had a median 21-day inpatient stay after admission for their hip fracture, so much of the rehabilitation included as inpatient care in the Japanese schema would be delivered in the outpatient setting in the United States, where the mean inpatient length of stay after hip fracture is about 5 days.
Patients aged 65 years and older were included in the study if they had a prefracture diagnosis of dementia and sustained a hip fracture that was surgically repaired. Patients with multiple fracture sites, those with incomplete data, and those who didn’t undergo surgery or died in the hospital were excluded from the study. Almost two-thirds of patients (65.7%) were aged 85 years or older, and about a third (36.6%) were living in nursing facilities at the time of fracture. About 60% of patients were assessed as having mild dementia – a classification requiring little assistance with ADLs – before admission.
The authors noted that their study broke out timing, duration, and frequency of rehabilitation separately, unlike some previous work. They posited that longer or more frequent rounds of rehabilitation may be particularly effective in patients with dementia, who may face some communication barriers and require reteaching.
The study was unrandomized by design, and unmeasured confounders may have affected the results, they noted. Also, the study wasn’t designed to detect whether patient factors such as premorbid functional status, level of dementia, or living situation affected the timing, duration, and intensity of rehabilitation they were provided. The investigators recommended randomized studies to validate the effect of early, intensive rehabilitation for hip fracture surgery in patients with dementia.
The study was funded by the Japanese Ministry of Health, Labor, and Welfare. The authors reported that they have no relevant conflicts of interest.
SOURCE: Uda K et al. Arch Phys Med Rehabil. 2019;100:2301-7.
according to a recent Japanese study in the Archives of Physical Medicine and Rehabilitation.
Looking at 43,506 patients cared for at 1,053 hospitals, Kazuaki Uda, MPH, and colleagues of the University of Tokyo found that scores on the Barthel Index, a measure of functional status, climbed significantly as the frequency and duration of postoperative rehabilitation increased. There was also a statistically significant, but small, association with improved functional status and early initiation of rehabilitation.
“Our results suggest that additional days of rehabilitation or an additional 20 minutes for each daily rehabilitation session in acute-care hospitals may provide better functional outcomes for patients with dementia,” concluded Mr. Uda and coinvestigators.
The Barthel Index (BI) measures independence in performing 10 activities of daily living (ADLs), including feeding, bathing, grooming, and dressing; bowel, bladder, and toileting; and transfers, mobility, and stair use. Each ADL is rate 0, 5, 10, or, for some, 15 points, and higher scores indicate more independence.
Compared with patients who received 3 days or fewer of rehabilitation weekly, patients receiving 3-4 days of rehabilitation saw an improvement of 2.62 on the BI. For those receiving 4-5 days, 5-6 days, and 6 or more days of rehabilitation, BI scores were higher by 5.83, 7.56, and 9.16, respectively. The results were statistically significant for all but the 3-4 day rehabilitation group.
Similarly, patients who received longer periods of rehabilitation saw more improvement in functional status. Compared with those who received 20-39 minutes per day of rehabilitation, those who received 40-59 minutes of therapy saw an increase of 4.37 on the BI, and those receiving an hour or more of therapy saw BI scores rise by 6.60 – both significant increases.
These results included a multivariable analysis that accounted for a number of patient characteristics such as comorbidities and body mass index, as well as fracture, fixation, and anesthesia type, and the interval from injury to surgery.
Representing the data in another way, the investigators found that “each increase in the average units of rehabilitation (units per day) was associated with a 5.46 increase in the BI.”
This retrospective cohort study, when placed in the context of previous work, suggests that “patients with cognitive impairment may benefit from rehabilitation for functional gains after hip fracture surgery in both acute and postacute settings,” the investigators wrote. They noted, however, that patients with dementia have often been excluded from larger outcome studies of hip fracture rehabilitation.
Patients in this study had a median 21-day inpatient stay after admission for their hip fracture, so much of the rehabilitation included as inpatient care in the Japanese schema would be delivered in the outpatient setting in the United States, where the mean inpatient length of stay after hip fracture is about 5 days.
Patients aged 65 years and older were included in the study if they had a prefracture diagnosis of dementia and sustained a hip fracture that was surgically repaired. Patients with multiple fracture sites, those with incomplete data, and those who didn’t undergo surgery or died in the hospital were excluded from the study. Almost two-thirds of patients (65.7%) were aged 85 years or older, and about a third (36.6%) were living in nursing facilities at the time of fracture. About 60% of patients were assessed as having mild dementia – a classification requiring little assistance with ADLs – before admission.
The authors noted that their study broke out timing, duration, and frequency of rehabilitation separately, unlike some previous work. They posited that longer or more frequent rounds of rehabilitation may be particularly effective in patients with dementia, who may face some communication barriers and require reteaching.
The study was unrandomized by design, and unmeasured confounders may have affected the results, they noted. Also, the study wasn’t designed to detect whether patient factors such as premorbid functional status, level of dementia, or living situation affected the timing, duration, and intensity of rehabilitation they were provided. The investigators recommended randomized studies to validate the effect of early, intensive rehabilitation for hip fracture surgery in patients with dementia.
The study was funded by the Japanese Ministry of Health, Labor, and Welfare. The authors reported that they have no relevant conflicts of interest.
SOURCE: Uda K et al. Arch Phys Med Rehabil. 2019;100:2301-7.
according to a recent Japanese study in the Archives of Physical Medicine and Rehabilitation.
Looking at 43,506 patients cared for at 1,053 hospitals, Kazuaki Uda, MPH, and colleagues of the University of Tokyo found that scores on the Barthel Index, a measure of functional status, climbed significantly as the frequency and duration of postoperative rehabilitation increased. There was also a statistically significant, but small, association with improved functional status and early initiation of rehabilitation.
“Our results suggest that additional days of rehabilitation or an additional 20 minutes for each daily rehabilitation session in acute-care hospitals may provide better functional outcomes for patients with dementia,” concluded Mr. Uda and coinvestigators.
The Barthel Index (BI) measures independence in performing 10 activities of daily living (ADLs), including feeding, bathing, grooming, and dressing; bowel, bladder, and toileting; and transfers, mobility, and stair use. Each ADL is rate 0, 5, 10, or, for some, 15 points, and higher scores indicate more independence.
Compared with patients who received 3 days or fewer of rehabilitation weekly, patients receiving 3-4 days of rehabilitation saw an improvement of 2.62 on the BI. For those receiving 4-5 days, 5-6 days, and 6 or more days of rehabilitation, BI scores were higher by 5.83, 7.56, and 9.16, respectively. The results were statistically significant for all but the 3-4 day rehabilitation group.
Similarly, patients who received longer periods of rehabilitation saw more improvement in functional status. Compared with those who received 20-39 minutes per day of rehabilitation, those who received 40-59 minutes of therapy saw an increase of 4.37 on the BI, and those receiving an hour or more of therapy saw BI scores rise by 6.60 – both significant increases.
These results included a multivariable analysis that accounted for a number of patient characteristics such as comorbidities and body mass index, as well as fracture, fixation, and anesthesia type, and the interval from injury to surgery.
Representing the data in another way, the investigators found that “each increase in the average units of rehabilitation (units per day) was associated with a 5.46 increase in the BI.”
This retrospective cohort study, when placed in the context of previous work, suggests that “patients with cognitive impairment may benefit from rehabilitation for functional gains after hip fracture surgery in both acute and postacute settings,” the investigators wrote. They noted, however, that patients with dementia have often been excluded from larger outcome studies of hip fracture rehabilitation.
Patients in this study had a median 21-day inpatient stay after admission for their hip fracture, so much of the rehabilitation included as inpatient care in the Japanese schema would be delivered in the outpatient setting in the United States, where the mean inpatient length of stay after hip fracture is about 5 days.
Patients aged 65 years and older were included in the study if they had a prefracture diagnosis of dementia and sustained a hip fracture that was surgically repaired. Patients with multiple fracture sites, those with incomplete data, and those who didn’t undergo surgery or died in the hospital were excluded from the study. Almost two-thirds of patients (65.7%) were aged 85 years or older, and about a third (36.6%) were living in nursing facilities at the time of fracture. About 60% of patients were assessed as having mild dementia – a classification requiring little assistance with ADLs – before admission.
The authors noted that their study broke out timing, duration, and frequency of rehabilitation separately, unlike some previous work. They posited that longer or more frequent rounds of rehabilitation may be particularly effective in patients with dementia, who may face some communication barriers and require reteaching.
The study was unrandomized by design, and unmeasured confounders may have affected the results, they noted. Also, the study wasn’t designed to detect whether patient factors such as premorbid functional status, level of dementia, or living situation affected the timing, duration, and intensity of rehabilitation they were provided. The investigators recommended randomized studies to validate the effect of early, intensive rehabilitation for hip fracture surgery in patients with dementia.
The study was funded by the Japanese Ministry of Health, Labor, and Welfare. The authors reported that they have no relevant conflicts of interest.
SOURCE: Uda K et al. Arch Phys Med Rehabil. 2019;100:2301-7.
REPORTING FROM THE ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
First-time marathon runners rewind the clock on vascular aging
Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.
Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.
Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.
“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”
The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.
Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.
Anthropometric data, peripheral BP, and aerobic capacity (peak VO2) were also assessed at both study points.
Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.
Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.
For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.
The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.
In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.
The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.
Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO2 didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.
The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.
Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”
The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.
SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.
Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.
Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.
Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.
“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”
The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.
Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.
Anthropometric data, peripheral BP, and aerobic capacity (peak VO2) were also assessed at both study points.
Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.
Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.
For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.
The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.
In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.
The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.
Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO2 didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.
The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.
Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”
The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.
SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.
Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.
Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.
Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.
“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”
The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.
Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.
Anthropometric data, peripheral BP, and aerobic capacity (peak VO2) were also assessed at both study points.
Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.
Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.
For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.
The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.
In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.
The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.
Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO2 didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.
The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.
Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”
The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.
SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Pelvic insufficiency fractures are common after chemoradiotherapy for cervical cancer
CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.
“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.
Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.
In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.
The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.
The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m2 of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.
Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m2.
Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.
Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.
Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.
Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.
Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.
Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.
CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.
“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.
Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.
In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.
The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.
The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m2 of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.
Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m2.
Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.
Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.
Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.
Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.
Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.
Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.
CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.
“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.
Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.
In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.
The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.
The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m2 of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.
Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m2.
Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.
Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.
The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.
Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.
Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.
Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.
Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.
REPORTING FROM RSNA 2019
Iscalimab normalizes thyroid hormone levels in some patients with Graves disease
CHICAGO – The investigational monoclonal antibody iscalimab reduced levels of thyroid hormone and thyroid-stimulating hormone–receptor antibodies (TSHR-Ab) in some patients with Graves disease in a small study.
Of 15 patients with Graves disease, 7 patients, or 47%, saw their thyroid hormone levels normalize, and levels of TSHR-Ab normalized in 4 patients, or 27% of the cohort. In addition, mean levels of a chemokine associated with Graves disease activity dropped.
“These results suggest that iscalimab may be an effective and attractive immunomodulation strategy for Graves disease,” said George Kahaly, MD, PhD, in his presentation of the phase 2 results at the annual meeting of the American Thyroid Association (J Clin Endocrinol Metab. 2019 Sep 12. doi: 10.1210/clinem/dgz013).
Overall, patients who responded had lower levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSHR-Ab and lower thyroid volume at baseline.
Iscalimab is a fully human monoclonal antibody that is active against the costimulatory protein CD40 that is present on the surface of antigen-presenting cells. Dr. Kahaly, professor of endocrinology at Johannes Gutenberg University Medical Center, Mainz, Germany, explained that in primate studies, iscalimab inhibits the T cell–dependent antibody response to an antigen, without depletion of B cells. However, iscalimab would be expected to block B-cell activation and differentiation, “leading to reduced de novo TSHR antibody production,” said Dr. Kahaly. Inhibition of T cell–dependent antibody response was seen when iscalimab was given at a dose of 3 mg/kg in healthy human study participants.
The study results presented by Dr. Kahaly were drawn from a single-arm, proof-of-concept study that enrolled 15 patients with Graves disease to 12 weeks of treatment with iscalimab. The participants were followed for an additional 24 weeks after receiving intravenous iscalimab at 10 mg/kg on study days 1, 15, 29, 57, and 85.
All participants were receiving beta blockers at enrollment; four patients had new-onset Graves disease, and the rest were experiencing a treatment relapse.
The participants were a median 49 years old, and all but two were female. One patient was Asian, and the remainder were white. They were mostly normal weight, with a mean body mass index of about 23 kg/m2.
A group of seven patients who were clear responders to iscalimab saw normalization of FT4 levels; of the eight patients considered to be nonresponders, six required rescue medication with antithyroid drugs.
For responders, the initial mean FT4 level was 33.5 pmol/L, whereas for nonresponders, it was 51.3 pmol/L (P less than .05). Similarly, mean FT3 levels were 13.6 pmol/L in responders, compared with 22 pmol/L in nonresponders (P less than .05).
Mean thyroid volume was 14.5 ml in responders, compared with 26 ml in nonresponders (P less than .005).
A subgroup of four patients within the responder group became TSHR-Ab negative, with sustained low antibody levels seen during the follow-up period. All but one of the eight nonresponders had initial TSHR-Ab levels of more than 20 U/L, whereas the seven responders began with TSHR-Ab levels of about 10 U/L or less. Mean TSHR-Ab levels at baseline were 5.6 IU/L for responders, compared with 27.3 IU/L for nonresponders (P less than .001).
Most responders also had lower initial levels of antithyroid peroxidase IgG antibodies, compared with the nonresponder group.
Levels of chemokine (motif C-X-C) ligand 13 (CXCL13) fell throughout the study period. Higher CXCL13 levels are associated with lymphocytic infiltrates seen in autoimmune thyroiditis.
Occupancy of CD40 was initially measured at week 4 of the study and it remained high until week 16, when free CD40 receptors rose rapidly for several participants in both the responder and nonresponder groups. “The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks,” wrote Dr. Kahaly and colleagues in the abstract accompanying the presentation.
In assessing CD40 target engagement, the investigators found that total soluble CD40 levels climbed during the treatment period, reaching peaks as high as 400-500 ng/mL, and then plummeted back to zero by study’s end for all participants.
A pharmacokinetic analysis revealed expected peaks of serum iscalimab after treatments, with levels dropping sharply at the end of the study period and falling to levels approaching zero by week 24 for most participants.
In terms of safety, 12 patients experienced at least one adverse event, with 3 participants reporting an episode of cystitis during the study. Fatigue, headache, insomnia, nausea, and viral upper respiratory infection were each reported by 2 patients. No injection site reactions were seen. All adverse events were mild or moderate, did not result in study withdrawal, and resolved by the end of the study period, Dr. Kahaly noted.
“These encouraging results suggest that iscalimab should be tested further to understand better its potential therapeutic benefit,” the investigators wrote.
The study was funded by Novartis, which is developing iscalimab for Graves disease, other autoimmune disorders, and as an antirejection drug for patients with kidney transplants.
CHICAGO – The investigational monoclonal antibody iscalimab reduced levels of thyroid hormone and thyroid-stimulating hormone–receptor antibodies (TSHR-Ab) in some patients with Graves disease in a small study.
Of 15 patients with Graves disease, 7 patients, or 47%, saw their thyroid hormone levels normalize, and levels of TSHR-Ab normalized in 4 patients, or 27% of the cohort. In addition, mean levels of a chemokine associated with Graves disease activity dropped.
“These results suggest that iscalimab may be an effective and attractive immunomodulation strategy for Graves disease,” said George Kahaly, MD, PhD, in his presentation of the phase 2 results at the annual meeting of the American Thyroid Association (J Clin Endocrinol Metab. 2019 Sep 12. doi: 10.1210/clinem/dgz013).
Overall, patients who responded had lower levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSHR-Ab and lower thyroid volume at baseline.
Iscalimab is a fully human monoclonal antibody that is active against the costimulatory protein CD40 that is present on the surface of antigen-presenting cells. Dr. Kahaly, professor of endocrinology at Johannes Gutenberg University Medical Center, Mainz, Germany, explained that in primate studies, iscalimab inhibits the T cell–dependent antibody response to an antigen, without depletion of B cells. However, iscalimab would be expected to block B-cell activation and differentiation, “leading to reduced de novo TSHR antibody production,” said Dr. Kahaly. Inhibition of T cell–dependent antibody response was seen when iscalimab was given at a dose of 3 mg/kg in healthy human study participants.
The study results presented by Dr. Kahaly were drawn from a single-arm, proof-of-concept study that enrolled 15 patients with Graves disease to 12 weeks of treatment with iscalimab. The participants were followed for an additional 24 weeks after receiving intravenous iscalimab at 10 mg/kg on study days 1, 15, 29, 57, and 85.
All participants were receiving beta blockers at enrollment; four patients had new-onset Graves disease, and the rest were experiencing a treatment relapse.
The participants were a median 49 years old, and all but two were female. One patient was Asian, and the remainder were white. They were mostly normal weight, with a mean body mass index of about 23 kg/m2.
A group of seven patients who were clear responders to iscalimab saw normalization of FT4 levels; of the eight patients considered to be nonresponders, six required rescue medication with antithyroid drugs.
For responders, the initial mean FT4 level was 33.5 pmol/L, whereas for nonresponders, it was 51.3 pmol/L (P less than .05). Similarly, mean FT3 levels were 13.6 pmol/L in responders, compared with 22 pmol/L in nonresponders (P less than .05).
Mean thyroid volume was 14.5 ml in responders, compared with 26 ml in nonresponders (P less than .005).
A subgroup of four patients within the responder group became TSHR-Ab negative, with sustained low antibody levels seen during the follow-up period. All but one of the eight nonresponders had initial TSHR-Ab levels of more than 20 U/L, whereas the seven responders began with TSHR-Ab levels of about 10 U/L or less. Mean TSHR-Ab levels at baseline were 5.6 IU/L for responders, compared with 27.3 IU/L for nonresponders (P less than .001).
Most responders also had lower initial levels of antithyroid peroxidase IgG antibodies, compared with the nonresponder group.
Levels of chemokine (motif C-X-C) ligand 13 (CXCL13) fell throughout the study period. Higher CXCL13 levels are associated with lymphocytic infiltrates seen in autoimmune thyroiditis.
Occupancy of CD40 was initially measured at week 4 of the study and it remained high until week 16, when free CD40 receptors rose rapidly for several participants in both the responder and nonresponder groups. “The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks,” wrote Dr. Kahaly and colleagues in the abstract accompanying the presentation.
In assessing CD40 target engagement, the investigators found that total soluble CD40 levels climbed during the treatment period, reaching peaks as high as 400-500 ng/mL, and then plummeted back to zero by study’s end for all participants.
A pharmacokinetic analysis revealed expected peaks of serum iscalimab after treatments, with levels dropping sharply at the end of the study period and falling to levels approaching zero by week 24 for most participants.
In terms of safety, 12 patients experienced at least one adverse event, with 3 participants reporting an episode of cystitis during the study. Fatigue, headache, insomnia, nausea, and viral upper respiratory infection were each reported by 2 patients. No injection site reactions were seen. All adverse events were mild or moderate, did not result in study withdrawal, and resolved by the end of the study period, Dr. Kahaly noted.
“These encouraging results suggest that iscalimab should be tested further to understand better its potential therapeutic benefit,” the investigators wrote.
The study was funded by Novartis, which is developing iscalimab for Graves disease, other autoimmune disorders, and as an antirejection drug for patients with kidney transplants.
CHICAGO – The investigational monoclonal antibody iscalimab reduced levels of thyroid hormone and thyroid-stimulating hormone–receptor antibodies (TSHR-Ab) in some patients with Graves disease in a small study.
Of 15 patients with Graves disease, 7 patients, or 47%, saw their thyroid hormone levels normalize, and levels of TSHR-Ab normalized in 4 patients, or 27% of the cohort. In addition, mean levels of a chemokine associated with Graves disease activity dropped.
“These results suggest that iscalimab may be an effective and attractive immunomodulation strategy for Graves disease,” said George Kahaly, MD, PhD, in his presentation of the phase 2 results at the annual meeting of the American Thyroid Association (J Clin Endocrinol Metab. 2019 Sep 12. doi: 10.1210/clinem/dgz013).
Overall, patients who responded had lower levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSHR-Ab and lower thyroid volume at baseline.
Iscalimab is a fully human monoclonal antibody that is active against the costimulatory protein CD40 that is present on the surface of antigen-presenting cells. Dr. Kahaly, professor of endocrinology at Johannes Gutenberg University Medical Center, Mainz, Germany, explained that in primate studies, iscalimab inhibits the T cell–dependent antibody response to an antigen, without depletion of B cells. However, iscalimab would be expected to block B-cell activation and differentiation, “leading to reduced de novo TSHR antibody production,” said Dr. Kahaly. Inhibition of T cell–dependent antibody response was seen when iscalimab was given at a dose of 3 mg/kg in healthy human study participants.
The study results presented by Dr. Kahaly were drawn from a single-arm, proof-of-concept study that enrolled 15 patients with Graves disease to 12 weeks of treatment with iscalimab. The participants were followed for an additional 24 weeks after receiving intravenous iscalimab at 10 mg/kg on study days 1, 15, 29, 57, and 85.
All participants were receiving beta blockers at enrollment; four patients had new-onset Graves disease, and the rest were experiencing a treatment relapse.
The participants were a median 49 years old, and all but two were female. One patient was Asian, and the remainder were white. They were mostly normal weight, with a mean body mass index of about 23 kg/m2.
A group of seven patients who were clear responders to iscalimab saw normalization of FT4 levels; of the eight patients considered to be nonresponders, six required rescue medication with antithyroid drugs.
For responders, the initial mean FT4 level was 33.5 pmol/L, whereas for nonresponders, it was 51.3 pmol/L (P less than .05). Similarly, mean FT3 levels were 13.6 pmol/L in responders, compared with 22 pmol/L in nonresponders (P less than .05).
Mean thyroid volume was 14.5 ml in responders, compared with 26 ml in nonresponders (P less than .005).
A subgroup of four patients within the responder group became TSHR-Ab negative, with sustained low antibody levels seen during the follow-up period. All but one of the eight nonresponders had initial TSHR-Ab levels of more than 20 U/L, whereas the seven responders began with TSHR-Ab levels of about 10 U/L or less. Mean TSHR-Ab levels at baseline were 5.6 IU/L for responders, compared with 27.3 IU/L for nonresponders (P less than .001).
Most responders also had lower initial levels of antithyroid peroxidase IgG antibodies, compared with the nonresponder group.
Levels of chemokine (motif C-X-C) ligand 13 (CXCL13) fell throughout the study period. Higher CXCL13 levels are associated with lymphocytic infiltrates seen in autoimmune thyroiditis.
Occupancy of CD40 was initially measured at week 4 of the study and it remained high until week 16, when free CD40 receptors rose rapidly for several participants in both the responder and nonresponder groups. “The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks,” wrote Dr. Kahaly and colleagues in the abstract accompanying the presentation.
In assessing CD40 target engagement, the investigators found that total soluble CD40 levels climbed during the treatment period, reaching peaks as high as 400-500 ng/mL, and then plummeted back to zero by study’s end for all participants.
A pharmacokinetic analysis revealed expected peaks of serum iscalimab after treatments, with levels dropping sharply at the end of the study period and falling to levels approaching zero by week 24 for most participants.
In terms of safety, 12 patients experienced at least one adverse event, with 3 participants reporting an episode of cystitis during the study. Fatigue, headache, insomnia, nausea, and viral upper respiratory infection were each reported by 2 patients. No injection site reactions were seen. All adverse events were mild or moderate, did not result in study withdrawal, and resolved by the end of the study period, Dr. Kahaly noted.
“These encouraging results suggest that iscalimab should be tested further to understand better its potential therapeutic benefit,” the investigators wrote.
The study was funded by Novartis, which is developing iscalimab for Graves disease, other autoimmune disorders, and as an antirejection drug for patients with kidney transplants.
REPORTING FROM ATA 2019
Albinism awareness goes global in dermatologists’ nonprofit work
A dermatologist-led nonprofit organization has entered into a
Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.
“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.
Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
Striving to do good work
Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.
Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.
“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.
“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.
Albinism is more common by a factor of about 10 in certain sub-Saharan African populations in Tanzania and Malawi, compared with worldwide prevalence. The condition is stigmatized, but people with albinism are also believed to possess some magical powers. People with albinism are attacked, maimed, and even killed for their body parts, which are used by traditional “witch doctors” in ceremonies designed to generate wealth and good fortune. Raping a woman with albinism is thought by some to cure HIV/AIDS and infertility.
If African individuals with albinism escapes these horrors, they are still at high risk of developing a disfiguring, or even fatal, skin cancer. Even in higher-resource countries and in places farther from the equator, though, people with albinism still need stringent sun-exposure precautions and frequent dermatologic surveillance.
Philanthropic work in dermatology
Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.
“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.
He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”
Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.
“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”
Dr. Colbert reported that he has no relevant conflicts of interest.
Standing Voice also provides resources in East Africa
The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.
Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.
This and other work by Standing Voice were on display in an exhibit at the World Congress of Dermatology meeting in Milan in June 2019. In an interview at the meeting, Dr. Sharp, who spent his childhood in East Africa, contrasted access to dermatology care in the United States and United Kingdom with that in Africa, where an entire country may have hardly more than a few dermatologists.
“I go about three times a year, for about a week,” explained Dr. Sharp. “I’ll do a workshop to teach basic skin surgery techniques – excisions and biopsies. Very simple stuff. I’ll teach skin grafting as well because some of these patients have large lesions that won’t close directly,” he said. “On the whole, we like to use good grafts, rather than flaps, because often a local flap is just moving sun-damaged skin.”
Many patients have to travel great distances to reach a facility where general anesthesia and a full operating room suite are available, resources that are in high demand in resource-restricted African nations, according to Dr. Sharp. Teaching African practitioners regional anesthesia techniques that can be used for skin cancer surgery also helps ensure that more patients with albinism and squamous cell carcinoma can be treated – and treated closer to home.
Dr. Sharp reported that he has no relevant conflicts of interest.
A dermatologist-led nonprofit organization has entered into a
Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.
“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.
Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
Striving to do good work
Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.
Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.
“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.
“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.
Albinism is more common by a factor of about 10 in certain sub-Saharan African populations in Tanzania and Malawi, compared with worldwide prevalence. The condition is stigmatized, but people with albinism are also believed to possess some magical powers. People with albinism are attacked, maimed, and even killed for their body parts, which are used by traditional “witch doctors” in ceremonies designed to generate wealth and good fortune. Raping a woman with albinism is thought by some to cure HIV/AIDS and infertility.
If African individuals with albinism escapes these horrors, they are still at high risk of developing a disfiguring, or even fatal, skin cancer. Even in higher-resource countries and in places farther from the equator, though, people with albinism still need stringent sun-exposure precautions and frequent dermatologic surveillance.
Philanthropic work in dermatology
Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.
“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.
He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”
Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.
“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”
Dr. Colbert reported that he has no relevant conflicts of interest.
Standing Voice also provides resources in East Africa
The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.
Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.
This and other work by Standing Voice were on display in an exhibit at the World Congress of Dermatology meeting in Milan in June 2019. In an interview at the meeting, Dr. Sharp, who spent his childhood in East Africa, contrasted access to dermatology care in the United States and United Kingdom with that in Africa, where an entire country may have hardly more than a few dermatologists.
“I go about three times a year, for about a week,” explained Dr. Sharp. “I’ll do a workshop to teach basic skin surgery techniques – excisions and biopsies. Very simple stuff. I’ll teach skin grafting as well because some of these patients have large lesions that won’t close directly,” he said. “On the whole, we like to use good grafts, rather than flaps, because often a local flap is just moving sun-damaged skin.”
Many patients have to travel great distances to reach a facility where general anesthesia and a full operating room suite are available, resources that are in high demand in resource-restricted African nations, according to Dr. Sharp. Teaching African practitioners regional anesthesia techniques that can be used for skin cancer surgery also helps ensure that more patients with albinism and squamous cell carcinoma can be treated – and treated closer to home.
Dr. Sharp reported that he has no relevant conflicts of interest.
A dermatologist-led nonprofit organization has entered into a
Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.
“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.
Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
Striving to do good work
Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.
Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.
“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.
“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.
Albinism is more common by a factor of about 10 in certain sub-Saharan African populations in Tanzania and Malawi, compared with worldwide prevalence. The condition is stigmatized, but people with albinism are also believed to possess some magical powers. People with albinism are attacked, maimed, and even killed for their body parts, which are used by traditional “witch doctors” in ceremonies designed to generate wealth and good fortune. Raping a woman with albinism is thought by some to cure HIV/AIDS and infertility.
If African individuals with albinism escapes these horrors, they are still at high risk of developing a disfiguring, or even fatal, skin cancer. Even in higher-resource countries and in places farther from the equator, though, people with albinism still need stringent sun-exposure precautions and frequent dermatologic surveillance.
Philanthropic work in dermatology
Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.
“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.
He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”
Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.
“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”
Dr. Colbert reported that he has no relevant conflicts of interest.
Standing Voice also provides resources in East Africa
The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.
Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.
This and other work by Standing Voice were on display in an exhibit at the World Congress of Dermatology meeting in Milan in June 2019. In an interview at the meeting, Dr. Sharp, who spent his childhood in East Africa, contrasted access to dermatology care in the United States and United Kingdom with that in Africa, where an entire country may have hardly more than a few dermatologists.
“I go about three times a year, for about a week,” explained Dr. Sharp. “I’ll do a workshop to teach basic skin surgery techniques – excisions and biopsies. Very simple stuff. I’ll teach skin grafting as well because some of these patients have large lesions that won’t close directly,” he said. “On the whole, we like to use good grafts, rather than flaps, because often a local flap is just moving sun-damaged skin.”
Many patients have to travel great distances to reach a facility where general anesthesia and a full operating room suite are available, resources that are in high demand in resource-restricted African nations, according to Dr. Sharp. Teaching African practitioners regional anesthesia techniques that can be used for skin cancer surgery also helps ensure that more patients with albinism and squamous cell carcinoma can be treated – and treated closer to home.
Dr. Sharp reported that he has no relevant conflicts of interest.
Patients need physicians who see – and feel – beyond the EMR
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
EXPERT ANALYSIS FROM RSNA 2019
Reward, decision-making brain regions altered in teens with obesity
CHICAGO – according to a Brazilian study that used MRI to detect these changes.
Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.
In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.
Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.
Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.
Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.
The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.
When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.
Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.
Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.
“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.
She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.
Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.
CHICAGO – according to a Brazilian study that used MRI to detect these changes.
Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.
In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.
Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.
Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.
Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.
The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.
When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.
Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.
Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.
“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.
She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.
Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.
CHICAGO – according to a Brazilian study that used MRI to detect these changes.
Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.
In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.
Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.
Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.
Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.
The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.
When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.
Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.
Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.
“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.
She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.
Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.
REPORTING FROM RSNA 2019
Oral contraceptive use associated with smaller hypothalamic and pituitary volumes
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
REPORTING FROM RSNA 2019
Gunshot wound victims are at high risk for readmission
CHICAGO –
A study of individuals at a single institution who were hospitalized and had a prior history of gunshot wound found some patterns of injury that set patients up for a greater likelihood of readmission.
In particular, patients who sustained visceral gunshot wounds were over six times more likely to be readmitted to the hospital, Corbin Pomeranz, MD, a radiology resident at Thomas Jefferson University, Philadelphia, said in an interview at the annual meeting of the Radiological Society of North America. Dr. Pomeranz led the retrospective study that begins to fill a knowledge gap about what happens over the long term to those who sustain gunshot wounds.
“There continues to be profound lack of substantial information related to gun violence, particularly in predicting long-term outcomes,” Dr. Pomeranz and coauthors wrote in the abstract accompanying the presentation.
The researchers performed a single-site retrospective analysis over 3 months in 2018, tapping into an imaging database and looking for inpatient imaging exams that were nonacute, but related to gunshot wounds. From this information, the researchers went back to the original gunshot wound injury imaging, and recorded the pattern of injury, classifying wounds as neurologic, vascular, visceral, musculoskeletal, or involving multiple systems.
The investigators were able to glean additional information including the initial admitting hospital unit, information about interval admissions or surgeries, and demographic data. Regarding the nature of the gunshot injury itself, Dr. Pomeranz and coauthors went back to the earlier imaging studies to note bullet morphology, recording whether the bullet was intact, deformed, or had splintered into shrapnel within injured tissues.
In all, 174 imaging studies involving 110 patients were examined. Men made up 92% of the study population; the average age was 49.7 years. Neurologic and visceral gunshot wounds were moderately correlated with subsequent readmission (r = .436; P less than .001). However, some of this effect was blunted when patient age was controlled for in the statistical analysis.
Patients who were initially admitted to the intensive care unit, and who presumably had more severe injuries, were also more likely to be readmitted (r = .494, P less than .001). Here, “controlling for age had very little effect on the strength of the relationship between these two variables,” noted Dr. Pomeranz and coauthors.
A more elaborate statistical model incorporated several independent variables including age, type of injury, and body region involved, as well as bullet morphology. In this model, visceral injury was the strongest predictor for readmission, with an odds ratio of 6.44.
Dr. Pomeranz said that both the initial gunshot wound and subsequent gaps in care can contribute to readmissions. A patient who has a spinal cord injury may not be reimbursed adequately for supportive cushioning, or an appropriate wheelchair, and so may require admission for decubitus ulcers.
The number of admissions for osteomyelitis, which made up more than half of the subsequent admissions, initially surprised Dr. Pomeranz, until he realized that lack of mobility and sensory losses from gunshot-induced spinal cord injuries could easily lead to nonhealing lower extremity wounds, with osteomyelitis as a sequela.
Several patients were admitted for small bowel obstructions with no interval surgery since treatment for the gunshot wound. These readmissions, said Dr. Pomeranz, were assessed as related to the gunshot wound since it’s extremely rare for a patient with no history of abdominal surgery and no malignancy to have a small bowel obstruction. Exploratory laparotomies are common in the context of abdominal trauma caused by gunshot wounds, and either the gunshot itself or the laparotomy was the likely cause of adhesions.
Dr. Pomeranz acknowledged the many limitations of the study, but pointed out that some will be addressed when he and his coauthors conduct a larger study they have planned to look at readmissions from gunshot wounds at multiple hospitals in the Philadelphia area. The small sample size in the current study meant that the impact of socioeconomic status and other lifestyle and social variables and comorbidities couldn’t be adequately addressed in the statistical analysis. By casting a wider net within the greater Philadelphia area, the investigators should be able to track patients who receive care in more than one hospital system, increasing participant numbers, he said.
“Morbidity and outcomes from gun violence can only be assessed after a firm understanding of injury patterns on imaging,” noted Dr. Pomeranz. He said that interdisciplinary research investigating individual and societal short- and long-term costs of gun violence is sorely needed to inform public policy.
Dr. Pomeranz reported no outside sources of funding and reported that he had no conflicts of interest.
SOURCE: Pomeranz C et al. RSNA 2019, Presentation HP226-SD-THA3.
CHICAGO –
A study of individuals at a single institution who were hospitalized and had a prior history of gunshot wound found some patterns of injury that set patients up for a greater likelihood of readmission.
In particular, patients who sustained visceral gunshot wounds were over six times more likely to be readmitted to the hospital, Corbin Pomeranz, MD, a radiology resident at Thomas Jefferson University, Philadelphia, said in an interview at the annual meeting of the Radiological Society of North America. Dr. Pomeranz led the retrospective study that begins to fill a knowledge gap about what happens over the long term to those who sustain gunshot wounds.
“There continues to be profound lack of substantial information related to gun violence, particularly in predicting long-term outcomes,” Dr. Pomeranz and coauthors wrote in the abstract accompanying the presentation.
The researchers performed a single-site retrospective analysis over 3 months in 2018, tapping into an imaging database and looking for inpatient imaging exams that were nonacute, but related to gunshot wounds. From this information, the researchers went back to the original gunshot wound injury imaging, and recorded the pattern of injury, classifying wounds as neurologic, vascular, visceral, musculoskeletal, or involving multiple systems.
The investigators were able to glean additional information including the initial admitting hospital unit, information about interval admissions or surgeries, and demographic data. Regarding the nature of the gunshot injury itself, Dr. Pomeranz and coauthors went back to the earlier imaging studies to note bullet morphology, recording whether the bullet was intact, deformed, or had splintered into shrapnel within injured tissues.
In all, 174 imaging studies involving 110 patients were examined. Men made up 92% of the study population; the average age was 49.7 years. Neurologic and visceral gunshot wounds were moderately correlated with subsequent readmission (r = .436; P less than .001). However, some of this effect was blunted when patient age was controlled for in the statistical analysis.
Patients who were initially admitted to the intensive care unit, and who presumably had more severe injuries, were also more likely to be readmitted (r = .494, P less than .001). Here, “controlling for age had very little effect on the strength of the relationship between these two variables,” noted Dr. Pomeranz and coauthors.
A more elaborate statistical model incorporated several independent variables including age, type of injury, and body region involved, as well as bullet morphology. In this model, visceral injury was the strongest predictor for readmission, with an odds ratio of 6.44.
Dr. Pomeranz said that both the initial gunshot wound and subsequent gaps in care can contribute to readmissions. A patient who has a spinal cord injury may not be reimbursed adequately for supportive cushioning, or an appropriate wheelchair, and so may require admission for decubitus ulcers.
The number of admissions for osteomyelitis, which made up more than half of the subsequent admissions, initially surprised Dr. Pomeranz, until he realized that lack of mobility and sensory losses from gunshot-induced spinal cord injuries could easily lead to nonhealing lower extremity wounds, with osteomyelitis as a sequela.
Several patients were admitted for small bowel obstructions with no interval surgery since treatment for the gunshot wound. These readmissions, said Dr. Pomeranz, were assessed as related to the gunshot wound since it’s extremely rare for a patient with no history of abdominal surgery and no malignancy to have a small bowel obstruction. Exploratory laparotomies are common in the context of abdominal trauma caused by gunshot wounds, and either the gunshot itself or the laparotomy was the likely cause of adhesions.
Dr. Pomeranz acknowledged the many limitations of the study, but pointed out that some will be addressed when he and his coauthors conduct a larger study they have planned to look at readmissions from gunshot wounds at multiple hospitals in the Philadelphia area. The small sample size in the current study meant that the impact of socioeconomic status and other lifestyle and social variables and comorbidities couldn’t be adequately addressed in the statistical analysis. By casting a wider net within the greater Philadelphia area, the investigators should be able to track patients who receive care in more than one hospital system, increasing participant numbers, he said.
“Morbidity and outcomes from gun violence can only be assessed after a firm understanding of injury patterns on imaging,” noted Dr. Pomeranz. He said that interdisciplinary research investigating individual and societal short- and long-term costs of gun violence is sorely needed to inform public policy.
Dr. Pomeranz reported no outside sources of funding and reported that he had no conflicts of interest.
SOURCE: Pomeranz C et al. RSNA 2019, Presentation HP226-SD-THA3.
CHICAGO –
A study of individuals at a single institution who were hospitalized and had a prior history of gunshot wound found some patterns of injury that set patients up for a greater likelihood of readmission.
In particular, patients who sustained visceral gunshot wounds were over six times more likely to be readmitted to the hospital, Corbin Pomeranz, MD, a radiology resident at Thomas Jefferson University, Philadelphia, said in an interview at the annual meeting of the Radiological Society of North America. Dr. Pomeranz led the retrospective study that begins to fill a knowledge gap about what happens over the long term to those who sustain gunshot wounds.
“There continues to be profound lack of substantial information related to gun violence, particularly in predicting long-term outcomes,” Dr. Pomeranz and coauthors wrote in the abstract accompanying the presentation.
The researchers performed a single-site retrospective analysis over 3 months in 2018, tapping into an imaging database and looking for inpatient imaging exams that were nonacute, but related to gunshot wounds. From this information, the researchers went back to the original gunshot wound injury imaging, and recorded the pattern of injury, classifying wounds as neurologic, vascular, visceral, musculoskeletal, or involving multiple systems.
The investigators were able to glean additional information including the initial admitting hospital unit, information about interval admissions or surgeries, and demographic data. Regarding the nature of the gunshot injury itself, Dr. Pomeranz and coauthors went back to the earlier imaging studies to note bullet morphology, recording whether the bullet was intact, deformed, or had splintered into shrapnel within injured tissues.
In all, 174 imaging studies involving 110 patients were examined. Men made up 92% of the study population; the average age was 49.7 years. Neurologic and visceral gunshot wounds were moderately correlated with subsequent readmission (r = .436; P less than .001). However, some of this effect was blunted when patient age was controlled for in the statistical analysis.
Patients who were initially admitted to the intensive care unit, and who presumably had more severe injuries, were also more likely to be readmitted (r = .494, P less than .001). Here, “controlling for age had very little effect on the strength of the relationship between these two variables,” noted Dr. Pomeranz and coauthors.
A more elaborate statistical model incorporated several independent variables including age, type of injury, and body region involved, as well as bullet morphology. In this model, visceral injury was the strongest predictor for readmission, with an odds ratio of 6.44.
Dr. Pomeranz said that both the initial gunshot wound and subsequent gaps in care can contribute to readmissions. A patient who has a spinal cord injury may not be reimbursed adequately for supportive cushioning, or an appropriate wheelchair, and so may require admission for decubitus ulcers.
The number of admissions for osteomyelitis, which made up more than half of the subsequent admissions, initially surprised Dr. Pomeranz, until he realized that lack of mobility and sensory losses from gunshot-induced spinal cord injuries could easily lead to nonhealing lower extremity wounds, with osteomyelitis as a sequela.
Several patients were admitted for small bowel obstructions with no interval surgery since treatment for the gunshot wound. These readmissions, said Dr. Pomeranz, were assessed as related to the gunshot wound since it’s extremely rare for a patient with no history of abdominal surgery and no malignancy to have a small bowel obstruction. Exploratory laparotomies are common in the context of abdominal trauma caused by gunshot wounds, and either the gunshot itself or the laparotomy was the likely cause of adhesions.
Dr. Pomeranz acknowledged the many limitations of the study, but pointed out that some will be addressed when he and his coauthors conduct a larger study they have planned to look at readmissions from gunshot wounds at multiple hospitals in the Philadelphia area. The small sample size in the current study meant that the impact of socioeconomic status and other lifestyle and social variables and comorbidities couldn’t be adequately addressed in the statistical analysis. By casting a wider net within the greater Philadelphia area, the investigators should be able to track patients who receive care in more than one hospital system, increasing participant numbers, he said.
“Morbidity and outcomes from gun violence can only be assessed after a firm understanding of injury patterns on imaging,” noted Dr. Pomeranz. He said that interdisciplinary research investigating individual and societal short- and long-term costs of gun violence is sorely needed to inform public policy.
Dr. Pomeranz reported no outside sources of funding and reported that he had no conflicts of interest.
SOURCE: Pomeranz C et al. RSNA 2019, Presentation HP226-SD-THA3.
REPORTING FROM RSNA 2019
Bethesda system underpredicts malignancy in pediatric thyroid tumors
CHICAGO –
Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.
Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.
To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.
In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.
A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.
All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”
The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.
- Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
- Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
- Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
- Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
- Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
- Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.
In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.
Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.
Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.
Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.
All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.
Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”
She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.
Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.
SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.
CHICAGO –
Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.
Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.
To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.
In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.
A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.
All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”
The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.
- Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
- Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
- Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
- Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
- Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
- Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.
In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.
Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.
Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.
Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.
All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.
Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”
She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.
Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.
SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.
CHICAGO –
Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.
Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.
To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.
In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.
A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.
All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”
The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.
- Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
- Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
- Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
- Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
- Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
- Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.
In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.
Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.
Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.
Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.
All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.
Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”
She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.
Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.
SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.
REPORTING FROM ATA 2019
Key clinical point: Pediatric thyroid nodule cytopathology classified according to the Bethesda system showed a higher rate of malignancy than that reported in adults.
Major finding: Of 203 nodules, 14 were Bethesda category IV (follicular neoplasm or suspicious for neoplasm), and 42.9% of those were malignant, compared with the 25%-40% expected in adults.
Study details: Retrospective, single-center review of 203 fine needle–aspirated samples from 171 pediatric patients with thyroid nodules tracked over a 16-year period.
Disclosures: Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.
Source: Johnson T et al. ATA 2019, Oral Abstract 34.