Same day yttrium-90 radioembolization with single photon emission computed tomography/computed tomography: An opportunity to improve care during the COVID-19 pandemic and beyond

BACKGROUNDThe coronavirus disease 2019 (COVID-19) pandemic has made it more challenging for patients to undergo yttrium-90 (Y-90) radioembolization (RE). Same day Y-90 RE provides an opportunity to minimize logistical challenges and infection risk associated with COVID-19, thus improving patient access. AIMTo describe the use of same day Y-90 RE with routine single photon emission computed tomography/computed tomography (SPECT/CT) in order to optimize therapy. METHODSAll patients were selected for Y-90 RE through a multidisciplinary tumor board, and were screened and tested for COVID-19 infection per institutional protocol. A same day procedure was developed, consisting of angiography, imaging, and Y-90 resin particle delivery. Routine SPECT/CT after technetium-99m macroaggregated albumin (Tc-99m MAA) administration was performed for assessment of arterial supply, personalized dosimetry, and extrahepatic activity. Post-treatment Y-90 bremsstrahlung SPECT/CT was performed for confirmation of particle delivery, by utilization of energy windowing to limit signal from previously administered Tc-99m MAA particles. RESULTSA total of 14 patients underwent same day Y-90 RE between March and June 2020. Mean lung shunt fraction was 6.13% (range 3.5%-13.1%). Y-90 RE was performed for a single lesion in 7 patients, while the remaining 7 patients had treatment of multifocal lesions. The largest lesion measured 8.3 cm. All patients tolerated the procedure well and were discharged the same day. CONCLUSIONSame day Y-90 RE with resin-based microspheres is feasible, and provides an opportunity to mitigate infection risk and logistical challenges associated with the COVID-19 pandemic and beyond. We recommend consideration of SPECT/CT, especially among patients with complex malignancies, for the potential to improve outcomes and eligibility of patients to undergo same day Y-90 RE.     

Human heart sarcolemmal sheath antibodies in children with non-suppurative sequelae of group A streptococcal infections: a follow up study.

The kinetics of the human heart sarcolemmal sheath antibody were studied in children with acute rheumatic fever who had no carditis, children with acute rheumatic fever who had carditis and developed rheumatic heart disease, and in children with acute poststreptococcal glomerulonephritis. The children with rheumatic fever and those who developed valvular heart disease were given continuous secondary antistreptococcal prophylaxis. The titre of antibody at onset was significantly higher than that of the controls in children with acute rheumatic fever and carditis and in children with acute poststreptococcal nephritis. The difference in the antibody titre between children with rheumatic fever who had no carditis and controls was not statistically significant. After a mean follow up of three years, however, a high titre was only maintained in children with rheumatic fever who developed valvular heart disease.     

Normalization of immune activation in lymphoid tissue following highly active antiretroviral therapy

Although significant progress has been made in understanding immune reconstitution in peripheral blood following highly active antiretroviral therapy (HAART), less is known about immune changes in lymphoid tissue. Here, the expression of cytokine proteins (interferon gamma [IFN-gamma], interleukin [IL]-2, IL-4, IL-10, IL-1alpha, and IL-1beta) and surface antigens (CD4, CD8, CD1a, CD68) as well as cellular proviral HIV-1 DNA were determined in sequential tonsil biopsies before and at 4, 12, and 48 to 56 weeks posttherapy by quantitative in situ image analysis and fluorescent in situ 5;-nuclease assay (FISNA). Despite plasma virus suppression, a fraction of tonsil cells harbored pro-viral DNA for up to 1 year. A fourfold to eightfold increase in CD8+ T cells in tissue compared with seronegative controls and an increased frequency of CD1a+ dendritic cells prior to HAART reached control levels at week 56. The frequency of IFN-gamma expressing cells was 10-to 15-fold higher than controls before therapy and was comparable with findings in seronegative controls by week 56. Elevated baseline expression of IL-1alpha and IL-1beta was reduced by week 4 but IL-1alpha levels remained elevated in 1 of 3 patients at week 56. These findings suggest that with effective viral suppression the immune system in tissue may return to a more resting state.     

Assessment of pelvic floor muscle function in women with and without low back pain using transabdominal ultrasound

Pelvic floor muscle (PFM) dysfunction has been recently associated with the development of low back pain (LBP). Transabdominal ultrasound imaging has been established as an appropriate method for visualizing and measuring PFM function. No study has directly evaluated PFM function in individuals with and without LBP. The purpose of this study was to investigate the PFM function in women with and without LBP using transabdominal ultrasound. Convenience sample of 40 non-pregnant female participated in the study. Subjects were categorized into two groups: with LBP (n = 20) and without LBP (n = 20). The amount of bladder base movement on ultrasound (normalized to body mass index) was measured in all subjects and considered as an indicator of PFM function. Statistical analysis (Independent t-test) revealed significant difference in transabdominal ultrasound measurements for PFM function between the two groups (P = 0.04, 95% CI of difference: 0.002–0.27).The results of this study indicate PFM dysfunction in individuals with LBP compared to those without LBP. The results could be beneficial to clinicians when assessing and prescribing therapeutic exercises for patients with LBP.     

Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential

PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho-guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature consisting of the presence of an area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which Galpha(12) and Galpha(13) can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK, and associate with Plexin B, a semaphorin receptor, which controls axon guidance during development, through their PDZ domain, thereby stimulating Rho. Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoGEF. Indeed, we observed that PDZ-RhoGEF and LARG can form homo- and hetero-oligomers, whereas p115RhoGEF can only homo-oligomerize, and that this intermolecular interaction was mediated by their unique C-terminal regions. Deletion of the C-terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic activity towards Rho in vitro, but resulted in a drastic increase in the ability to stimulate a serum response element reporter and the accumulation of the GTP-bound Rho in vivo. Furthermore, removal of the C-termini of each of the three RGL-containing GEFs unleashed their full transforming potential. Together, these findings suggest the existence of a novel mechanism controlling the activity of PDZ-RhoGEF, LARG, and p115RhoGEF, which involves homo- and hetero-oligomerization through their inhibitory C-terminal region.