8 research outputs found
Transplant Physicians’ Attitudes on Candidacy for Allogeneic Hematopoietic Cell Transplantation (HCT) in Older Patients: The Need for a Standardized Geriatric Assessment (GA) Tool
Background
Despite improvements in conditioning regimens and supportive care having expanded the curative potential of HCT, underutilization of HCT in older adults persists (Bhatt VR et al, BMT 2017). Therefore, we conducted a survey of transplant physicians (TP) to determine their perceptions of the impact of older age (≥60 years) on HCT candidacy and utilization of tools to gauge candidacy.
Methods
We conducted a 23-item, online cross-sectional survey of adult physicians recruited from the Center for International Blood and Marrow Transplant Research between May and July 2019.
Results
175/770 (22.7%) TP completed the survey; majority of respondents were 41-60 years old, male, and practicing in a teaching hospital. Over 75% were at centers performing ≥50 HCT per year. When considering regimen intensity, most (96%, n=168) had an upper age limit (UAL) for using a myeloablative regimen (MAC), with only 29 physicians (17%) stating they would consider MAC for patients ≥70 years. In contrast, when considering a reduced intensity/non-myeloablative conditioning (RIC/NMA), 8%, (n=13), 54% (n=93), and 20% (n=35) stated that age 70, 75, and 80 years respectively would be the UAL to use this approach, with 18% (n=31) reporting no UAL. TP agreed that Karnofsky Performance Score (KPS) could exclude older pts for HCT, with 39.1% (n=66), 42.6% (n=72), and 11.4% (n=20) requiring KPS of ≥70, 80, and 90, respectively. The majority (n=92, 52.5%) indicated an HCT-comorbidity index threshold for exclusion, mostly ranging from ≥3 to ≥ 5. Almost all (89.7%) endorsed the need for a better health assessment of pre-HCT vulnerabilities to guide candidacy for pts ≥60 with varied assessments being utilized beyond KPS (Figure 1). However, the majority of centers rarely (33.1%) or never (45.7%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 yrs. The largest barriers to performing GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff (Figure 2). Approximately half (n=78, 45%) endorsed GA now routinely influences candidacy.
Conclusions
The vast majority of TP will consider RIC/NMA alloHCT for patients ≥70 years. However, there is heterogeneity in assessing candidacy. Incorporation of GA into a standardized and easily applied health assessment tool for risk stratification is an unmet need. The recently opened BMT CTN 1704 may aid in addressing this gap
Assessment of abdominal aortic aneurysm biology using magnetic resonance imaging and positron emission tomography-computed tomography.
Background
Although abdominal aortic aneurysm (AAA) growth is non-linear, serial
measurements of aneurysm diameter are the mainstay of aneurysm surveillance and
contribute to decisions on timing of intervention. Aneurysm biology plays a key part
in disease evolution but is not currently routinely assessed in clinical practice.
Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computed
Tomography (PET-CT) provide insight into disease processes on a cellular or
molecular level, and represent exciting new imaging biomarkers of disease activity.
Macrophage-mediated inflammation may be assessed using ultrasmall
superparamagnetic particles of iron oxide (USPIO) MRI and the PET radiotracer 18FSodium
Fluoride (18F-NaF) identifies microcalcification which is a response to
underlying necrotic inflammation. The central aim of this thesis was to investigate
these imaging modalities in patients with AAA.
Methods and Results
USPIO MRI: MULTI-CENTRE STUDY
In a prospective multi-centre observational cohort study, 342 patients (85.4% male,
mean age 73.1±7.2 years, mean AAA diameter 49.6±7.7mm) with asymptomatic
AAA ≥4 cm anteroposterior diameter underwent MRI before and 24-36 hours after
intravenous administration of USPIO. Colour maps (depicting the change in T2*
caused by USPIO) were used to classify aneurysms on the basis of the presence of
USPIO uptake in the aneurysm wall, representing mural inflammation. Intra- and
inter-observer agreement were found to be very good, with proportional agreement
of 0.91 (kappa 0.82) and 0.83 (kappa 0.66), respectively. At 1 year, there was 29.3%
discordant classification of aneurysms on repeated USPIO MRI and at 2 years,
discordance was 65%, suggesting that inflammation evolves over time. In the
observational study, after a mean of 1005±280 days of follow up, there were 126
(36.8%) aneurysm repairs and 17 (5.0%) ruptures. Participants with USPIO
enhancement (42.7%) had increased aneurysm expansion rates (3·1±2·5 versus
2·5±2·4 mm/year; difference 0·6 [95% confidence intervals (CI), 0·02 to 1·2]
mm/year, p=0·0424) and had higher rates of aneurysm rupture or repair
(69/146=47·3% versus 68/191=35·6%; difference 11·7%, 95% CI 1·1 to 22·2%,
p=0·0308). USPIO MRI was therefore shown to predict AAA expansion and the
composite of rupture or repair, however this was not independent of aneurysm
diameter (c-statistic, 0·7924 to 0·7926; unconditional net reclassification -13·5%,
95% confidence intervals -36·4% to 9·3%).
18F-NaF PET-CT: SINGLE-CENTRE STUDY
A sub-group of 76 patients also underwent 18F-NaF PET-CT, which was evaluated
using the maximum tissue-to-background ratio (TBRmax) in the most diseased
segment (MDS), a technique that showed very good intra- (ICC 0.70-0.89) and inter-observer
(ICC 0.637-0.856) agreement. Aneurysm tracer uptake was compared
firstly in a case-control study, with 20 patients matched to 20 control patients for age,
sex and smoking status. 18F-NaF uptake was higher in aneurysm when compared to
control aorta (log2TBRmax 1.712±0.560 vs. 1.314±0.489; difference 0.398 (95% CI
0.057, 0.739), p=0.023), or to non-aneurysmal aorta in patients with AAA
(log2TBRmax 1.647±0.537 vs. 1.332±0.497; difference 0.314 (95% CI 0.0685, 0.560),
p=0.004). An ex vivo study was performed on aneurysm and control tissue, which
demonstrated that 18F-NaF uptake on microPET-CT was higher in the aneurysm
hotspots and higher in aneurysm tissue compared to control tissue. Histological
analysis suggested that 18F-NaF was highest in areas of focal calcification and
necrosis. In an observational cohort study, aneurysms were stratified by tertiles of
TBRmax in the MDS and followed up for 510±196 days, with 6 monthly serial
ultrasound measurements of diameter. Those in the highest tertile of tracer uptake
expanded more than 2.5 times more rapidly than those in the lowest tertile (3.10
[3.58] mm/year vs. 1.24 [2.41] mm/year, p=0.008) and were also more likely to
experience repair or rupture (15.3% vs. 5.6%, log-rank p=0.043). In multivariable
analyses, 18F-NaF uptake on PET-CT emerged as an independent predictor of AAA
expansion (p=0.042) and rupture or repair (HR 2.49, 95% CI1.07, 5.78; p=0.034),
even when adjusted for age, sex, body mass index, systolic blood pressure, current
smoking and, crucially, aneurysm diameter.
Conclusion
These are the largest USPIO MRI and PET-CT studies in AAA disease to date and
the first to investigate 18F-NaF. Both USPIO MRI and 18F-NaF PET-CT are able to
predict AAA expansion and the composite of rupture and repair, with 18F-NaF PETCT
emerging as the first imaging biomarker that independently predicts expansion
and AAA events, even after adjustment for aneurysm diameter. This represents an
exciting new predictor of disease progression that adds incremental value to standard
clinical assessments. Feasibility and randomised clinical trials are now required to
assess the potential of this technique to change the management and outcome of patients with AAA
Out There: The Open Museum: Pushing the Boundaries of Museums' Potential
No abstract available
Out There: The Open Museum: Pushing the Boundaries of Museums' Potential
No abstract available