Therapeutic hypothermia is standard of care for infants with hypoxic ischemic encephalopathy. Murine models of hypoxic-ischemic injury exist; however, a well-established mouse model of therapeutic hypothermia following hypoxic-ischemic injury is lacking. The goal of this study was to develop a full-term-equivalent murine model of therapeutic hypothermia after hypoxia-ischemia and examine magnetic resonance imaging, behavior, and histology in a region and sex specific manner. Hypoxic-ischemic injury was induced at postnatal day 10 in C57BL6 mice using a modified Vannucci model. Mice were randomized to control, hypothermia (31˚C for 4h), or normothermia (36˚C) following hypoxic-ischemic injury and stratified by sex. T2-weighted magnetic resonance imaging was obtained at postnatal day 18 and 30 and regional and total cerebral and cerebellar volumes measured. Behavioral assessments were performed on postnatal day 14, 21, and 28. On postnatal day 18, normothermic mice had smaller cerebral volumes (p < 0.001 vs. controls and p = 0.009 vs. hypothermia), while at postnatal day 30 both injured groups had smaller volumes than controls. When stratified by sex, only normothermia treated male mice had smaller cerebral volumes (p = 0.001 vs. control; p = 0.008 vs. hypothermia) at postnatal day 18, which persisted at postnatal day 30 (p = 0.001 vs. control). Female mice had similar cerebral volumes between groups at both day 18 and 30. Cerebellar volumes of hypothermia treated male mice differed from control at day 18, but not at 30. Four hours of therapeutic hypothermia in this murine hypoxic-ischemic injury model provides sustained neuroprotection in the cerebrum of male mice. Due to variable degree of injury in female mice, response to therapeutic hypothermia is difficult to discern. Deficits in female behavior tests are not fully explained by imaging measures and likely represent injury not detectable by volume measurements alone.
Background and Objectives: The COVID-19 pandemic required rapid adaptation of multidisciplinary tumor board conferences to a virtual setting; however, there are little data describing the benefits and challenges of using such a platform.Methods: An anonymous quality improvement survey was sent to participants of tumor board meetings at a large academic institution. Participants answered questions pertaining to the relative strengths and weaknesses of in-person and virtual settings.Results: A total of 335 responses (23.3% response rate) were recorded, and 253 met inclusion criteria. Respondents represented 25 different tumor board meetings, with colorectal, breast, and liver (18.6%, 17.0%, and 13.0%, respectively) being the most commonly attended. Virtual tumor boards were equivalent to in-person across 9 of 10 domains queried, while a virtual format was preferred for participation in off-site tumor boards. The lack of networking opportunities was ranked by physicians to be a significant challenge of the virtual format. Consistent leadership and organization, engaged participation of all attendees, and upgrading technology infrastructure were considered critical for success of virtual meetings.
Conclusions:The implementation of virtual tumor board meetings has been associated with numerous challenges. However, improving several key aspects can improve participant satisfaction and ensure excellent patient care.
Enhanced vascular permeability in tumors plays an essential role in nanoparticle delivery. Prostate-specific membrane antigen (PSMA) is overexpressed on the epithelium of aggressive prostate cancers (PCs). Here, we evaluated the feasibility of increasing the delivery of PSMA-targeted magnetic nanoparticles (MNPs) to tumors by enhancing vascular permeability in PSMA(+) PC tumors with PSMA-targeted photodynamic therapy (PDT).
Method:
PSMA(+) PC3 PIP tumor-bearing mice were given a low-molecular-weight PSMA-targeted photosensitizer and treated with fluorescence image-guided PDT, 4 h after. The mice were then given a PSMA-targeted MNP immediately after PDT and monitored with fluorescence imaging and T
2
-weighted magnetic resonance imaging (T
2
-W MRI) 18 h, 42 h, and 66 h after MNP administration. Untreated PSMA(+) PC3 PIP tumor-bearing mice were used as negative controls.
Results:
An 8-fold increase in the delivery of the PSMA-targeted MNPs was detected using T
2
-W MRI in the pretreated tumors 42 h after PDT, compared to untreated tumors. Additionally, T
2
-W MRIs revealed enhanced peripheral intra-tumoral delivery of the PSMA-targeted MNPs. That finding is in keeping with two-photon microscopy, which revealed higher vascular densities at the tumor periphery.
Conclusion:
These results suggest that PSMA-targeted PDT enhances the delivery of PSMA-targeted MNPs to PSMA(+) tumors by enhancing the vascular permeability of the tumors.
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