The value of 99mTc-MAA SPECT/CT for lung shunt estimation in 90Y radioembolization: a phantom and patient study

Abstract Background A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of 90Y microspheres. Currently, 99mTc macroaggregated albumin (99mTc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from 99mTc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from 99mTc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared. Results A liver/lung torso phantom filled with 99mTc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with 90Y PET/CT-based measurements. In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between 99mTc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3–29.4) for planar imaging and 3.2 Gy (range 0.4–13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from 90Y PET/CT was 1.0%, (range 0.3–2.8). This value was not significantly different from the mean LSF estimate from 99mTc-MAA SPECT/CT (mean 1.0%, range 0.4–1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2–15.0; p = 0.0002). Conclusions The improved accuracy demonstrated by the phantom study, agreement with 90Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that 99mTc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.https://deepblue.lib.umich.edu/bitstream/2027.42/144504/1/13550_2018_Article_402.pd

Longitudinal Invariance Testing Of The Knee Injury Osteoarthritis Outcome Score For Joint Replacement Scale (KOOS-JR)

# Background The Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) is a seven-item patient reported outcome measure used to assess perceived knee health. Though commonly used, the longitudinal psychometric properties of the KOOS-JR have not been established and further characterization of its structural validity and multi-group invariance properties is warranted. # Purpose The purpose of this study was to evaluate psychometric properties of the KOOS-JR in a large sample of patients who received care for knee pathology. # Study Design Original research. # Methods Longitudinal data extracted from the Surgical Outcome System (SOS) database of 13,470 knee pathology patients who completed the KOOS-JR at baseline, three-months, six- months, and one-year. Scale structure was assessed with confirmatory factor analysis (CFA), while multi-group and longitudinal invariance properties were assessed with CFA-based procedures. Latent group means were compared with statistical significance set at α ≤ .05 and Cohen’s d effect size as d = 0.2 (small), d = 0.5 (medium), and d = 0.8 (large). # Results CFA results exceeded goodness-of-fit indices at all timepoints. Multi-group invariance properties passed test requirements. Longitudinal analysis identified a biased item resulting in removal of item #1; the retained six-item model (KOOS-JR-6) passed longitudinal invariance requirements. KOOS-JR-6 scores significantly changed over time (p ≤ .001, Mdiff = 1.08, Cohen’s d = 0.57): the highest scores were at baseline examination and the lowest at 12-month assessment. # Conclusions The KOOS-JR can be used to assess baseline differences between males and females, middle and older aged adults, and patients receiving total knee arthroplasty or non-operative care. Caution is warranted if the KOOS-JR is used longitudinally due to potential measurement error associated with item #1. The KOOS-JR-6 may be a more viable option to assess change over time; however, more research is warranted. # Level of Evidence 3 © The Author(s

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct

The mediating role of discrete emotions in the relationship between injustice and counterproductive work behaviors:a study in Pakistan

Purpose: Our study explores the mediating role of discrete emotions in the relationships between employee perceptions of distributive and procedural injustice, regarding an annual salary raise, and counterproductive work behaviors (CWBs). Design/Methodology/Approach: Survey data were provided by 508 individuals from telecom and IT companies in Pakistan. Confirmatory factor analysis, structural equation modeling, and bootstrapping were used to test our hypothesized model. Findings: We found a good fit between the data and our tested model. As predicted, anger (and not sadness) was positively related to aggressive CWBs (abuse against others and production deviance) and fully mediated the relationship between perceived distributive injustice and these CWBs. Against predictions, however, neither sadness nor anger was significantly related to employee withdrawal. Implications: Our findings provide organizations with an insight into the emotional consequences of unfair HR policies, and the potential implications for CWBs. Such knowledge may help employers to develop training and counseling interventions that support the effective management of emotions at work. Our findings are particularly salient for national and multinational organizations in Pakistan. Originality/Value: This is one of the first studies to provide empirical support for the relationships between in/justice, discrete emotions and CWBs in a non-Western (Pakistani) context. Our study also provides new evidence for the differential effects of outward/inward emotions on aggressive/passive CWBs

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits - the Hispanic/Latino Anthropometry Consortium

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,771) and generalized our findings in 9 additional studies (HISLA Stage 2, n=10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification