IMPORTANCE Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of <30 mL/min/1.73 m 2 ) who receive a group II gadolinium-based contrast agent (GBCA) is not well understood or summarized in the literature.OBJECTIVE To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA. DATA SOURCES A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations.STUDY SELECTION Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded.DATA EXTRACTION AND SYNTHESIS Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis. MAIN OUTCOMES AND MEASURESPooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs. RESULTSSixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and gadoteridol (0 of 230; upper bound of 95% CI, 1.59%).CONCLUSIONS AND RELEVANCE This study's findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population.

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Promising recent investigations have shown that breast malignancies exhibit restricted diffusion on diffusion-weighted imaging (DWI) and may be distinguished from normal tissue and benign lesions in the breast based on differences in apparent diffusion coefficient (ADC) values. In this study, we assessed the influence of intravoxel fat signal on breast diffusion measures by comparing ADC values obtained using a diffusion-weighted single shot fast spin echo sequence with and without fat suppression. The influence of breast density on ADC measures was also evaluated. ADC values were calculated for both tumor and normal fibroglandular tissue in a group of twenty-one women with diagnosed breast cancer. There were systematic underestimations of ADC for both tumor and normal breast tissue due to intravoxel contribution from fat signal on non-fat-suppressed DWI. This ADC underestimation was more pronounced for normal tissue values (mean difference = 40%) than for tumors (mean difference = 27%, p<0.001) and was worse in women with low breast tissue density versus those with extremely dense breasts (p<0.05 for both tumor and normal tissue). Tumor conspicuity measured by contrast-to-noise ratio was significantly higher on ADC maps created with fat suppression and was not significantly associated with breast density. In summary, robust fat suppression is important for accurate breast ADC measures and optimal lesion conspicuity on DWI.

Rationale and Objectives The aim of this work was to compare a high-resolution diffusion-weighted imaging (HR-DWI) acquisition (voxel size = 4.8 mm3) to a standard diffusion-weighted imaging (STD-DWI) acquisition (voxel size = 29.3 mm3) for monitoring neoadjuvant therapy-induced changes in breast tumors. Materials and Methods Nine women with locally advanced breast cancer were imaged with both HR-DWI and STD-DWI before and after 3 weeks (early treatment) of neoadjuvant taxane-based treatment. Tumor apparent diffusion coefficient (ADC) metrics (mean and histogram percentiles) from both DWI methods were calculated, and their relationship to tumor volume change after 12 weeks of treatment (posttreatment) measured by dynamic contrast enhanced magnetic resonance imaging was evaluated with a Spearman’s rank correlation. Results The HR-DWI pretreatment 15th percentile tumor ADC (P = .03) and early treatment 15th, 25th, and 50th percentile tumor ADCs (P = .008, .010, .04, respectively) were significantly lower than the corresponding STD-DWI percentile ADCs. The mean tumor HR-ADC was significantly lower than STD-ADC at the early treatment time point (P = .02), but not at the pretreatment time point (P = .07). A significant early treatment increase in tumor ADC was found with both methods (P < .05). Correlations between HR-DWI tumor ADC and posttreatment tumor volume change were higher than the STD-DWI correlations at both time points and the lower percentile ADCs had the strongest correlations. Conclusion These initial results suggest that the HR-DWI technique has potential for improving characterization of low tumor ADC values over STD-DWI and that HR-DWI may be of value in evaluating tumor change with treatment.

Purpose: To present a novel technique for measuring tissue enhancement in breast fibroglandular tissue regions on contrast-enhanced breast magnetic resonance imaging (MRI) aimed at quantifying the enhancement of breast parenchyma, also known as ''background enhancement.'' Materials and Methods: Our quantitative method for measuring breast MRI background enhancement was evaluated in a population of 16 healthy volunteers. We also demonstrate the use of our new technique in the case study of one subject classified as high risk for developing breast cancer who underwent 3 months of tamoxifen therapy.Results: We obtained quantitative measures of background enhancement in all cases. The high-risk patient exhibited a 37% mean reduction in background enhancement with treatment. Conclusion:Our quantitative method is a robust and promising tool that may allow investigators to quantify and document the potential adverse effect of background enhancement on diagnostic accuracy in larger populations.

BackgroundA significant proportion of patients with advanced cancer undergo palliative radiotherapy (RT) within their last 30 days of life. This study characterizes palliative RT at our institution and aims to identify patients who may experience limited benefit from RT due to imminent mortality.MethodsFive hundred and-eighteen patients treated with external beam RT to a site of metastatic disease between 2012 and 2016 were included. Mann-Whitney U and chi-squared tests were used to identify factors associated with RT within 30 days of death (D30RT).ResultsMedian age at RT was 63 years (IQR 54–71). Median time from RT to death was 74 days (IQR 33–174). One hundred and twenty-five patients (24%) died within 30 days of RT. D30RT was associated with older age at RT (64 vs. 62 years, p = 0.04), shorter interval since diagnosis (14 vs. 31 months, p <  0.001), liver metastasis (p = 0.02), lower KPS (50 vs. 70, p <  0.001), lower BMI (22 vs. 24, p = 0.001), and inpatient status at consult (56% vs. 26%, p < 0.001). Patients who died within 30 days of RT were less likely to have hospice involved in their care (44% vs. 71%, p = 0.001). D30RT was associated with higher Chow and TEACHH scores at consult (p < 0.001 for both).ConclusionsTwenty-four percent of patients received palliative RT within 30 days of death. Additional tools are necessary to help physicians identify patients who would benefit from short treatment courses or alternative interventions to maximize quality at the end of life.

The N-phenethyl analogues of (1R*,4aR*,9aS*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol and 8-ol and (1R*,4aR*,9aR*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2.3-c]pyridin-6-ol and 8-ol, the ortho-(43) and parahydroxy e-(20), and f-oxide-bridged 5-phenylmorphans (53 and 26) were prepared in racemic and enantiomerically pure forms from a common precursor, the quaternary salt 12. Optical resolutions were accomplished by salt formation with suitable enantiomerically pure chiral acids or by preparative HPLC on a chiral support. The N-phenethyl (−)-para-e enantiomer (1S,4aS,9aR-(−)-20) was found to be a μ-opioid agonist with morphine-like antinociceptive activity in a mouse assay. In contrast, the N-phenethyl (−)-ortho-f enantiomer (1R,4aR,9aR-(−)-53) had good affinity for the μ-opioid receptor (Ki = 7 nM) and was found to be a μ-antagonist both in the [ 35 S]GTP-γ-S assay and in vivo. The molecular structures of these rigid enantiomers were energy minimized with density functional theory at the level B3LYP/6-31G* level, and then overlayed on a known potent μ-agonist. This superposition study suggests that the agonist activity of the oxide-bridged 5-phenylmorphans can be attributed to formation of a seven membered ring that is hypothesized to facilitate a proton transfer from the protonated nitrogen to a proton acceptor in the μ-opioid receptor.

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