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Abstract Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706 .

(1) Background: Climate change is increasing the already frequent diverse extreme weather events (EWE) across geographic locations, directly and indirectly impacting human health. However, current ongoing research fails to address the magnitude of these indirect impacts, including healthcare access. Vulnerable populations such as persons with spinal cord injury (pSCI) face added physiologic burden such as thermoregulation or mobility challenges like closure of public transportation. Our exploratory research assessed commute and transport to healthcare facilities as well as the knowledge, attitudes and behaviors (KAB) of pSCI regarding EWE and climate change when compared to pSCI caregivers (CG) and the general public (GP). (2) Methods: A KAB survey was employed to conduct a cross-sectional assessment of pSCI, CG, and GP in Miami from October through November 2019 using snowball sampling. Descriptive and logistic regression statistical analyses were used. (3) Results: Of 65 eligible survey respondents, 27 (41.5%) were pSCI, 11 (17%) CG, and 27 (41.5%) GP. Overall, pSCI reported EWE, particularly flooding and heavy rain, affecting their daily activities including healthcare appointments, more frequently than CG or GP. The overall models for logistic regression looking at commute to and attendance of healthcare appointments were statistically significant. pSCI self-report being less vulnerable than others, and a large proportion of each group was not fully convinced climate change is happening. (4) Conclusions: This study provided insight to the KAB of 3 population subgroups in Miami, Florida. pSCI are significantly more vulnerable to the effects of regional weather events yet exhibit disproportionate self-perception of their vulnerability. Continued and more comprehensive research is needed to characterize the barriers that vulnerable populations face during weather events.

Eye tracking assessments are clinician dependent and can contribute to misclassification of coma. We investigated responsiveness to videos with and without audio in traumatic brain injury (TBI) subjects using video eye-tracking (VET). We recruited 20 healthy volunteers and 10 unresponsive TBI subjects. Clinicians were surveyed whether the subject was tracking on their bedside assessment. The Coma Recovery Scale-Revised (CRS-R) was also performed. Eye movements in response to three different 30-second videos with and without sound were recorded using VET. The videos consisted of moving characters (a dancer, a person skateboarding, and Spiderman). Tracking on VET was defined as visual fixation on the character and gaze movement in the same direction of the character on two separate occasions. Subjects were classified as "covert tracking" (tracking using VET only), "overt tracking" (VET and clinical exam by clinicians), and "no tracking". A k-nearest-neighbors model was also used to identify tracking computationally. Thalamocortical connectivity and structural integrity were evaluated with EEG and MRI. The ability to obey commands was evaluated at 6- and 12-month follow-up. The average age was 29 (± 17) years old. Three subjects demonstrated "covert tracking" (CRS-R of 6, 8, 7), two "overt tracking" (CRS-R 22, 11), and five subjects "no tracking" (CRS-R 8, 6, 5, 6, 7). Among the 84 tested trials in all subjects, 11 trials (13%) met the criteria for "covert tracking". Using the k-nearest approach, 14 trials (17%) were classified as "covert tracking". Subjects with "tracking" had higher thalamocortical connectivity, and had fewer structures injured in the eye-tracking network than those without tracking. At follow-up, 2 out of 3 "covert" and all "overt" subjects recovered consciousness versus only 2 subjects in the "no tracking" group. Immersive stimuli may serve as important objective tools to differentiate subtle tracking using VET.

Objective: Limited data are available on posttraumatic stress symptoms (PTSS) among COVID-19 survivors. This study aimed to contribute to this knowledge base., Methods: PTSS among COVID-19 survivors who had been hospitalized were investigated. Patients were identified as COVID-19 positive at hospital admission. COVID-19 survivors were surveyed with the Posttraumatic Stress Disorder Checklist (PCL-5) between March and October 2020 at 5- and 12-month postdischarge follow-up points., Results: Of 411 patients, 331 (81%) survived to hospital discharge. Of these survivors, 83 (25%) completed the PCL-5 at the 5-month follow-up. Of those patients, 12 (14%) screened positive for PTSS. At the 12-month follow-up, four of eight patients remained PTSS positive. Mean age of follow-up participants was 62±15 years; 47% were women, 65% were White, and 63% were Hispanic. PTSS-positive patients were predominantly non-White (67% vs. 30%, p=0.02), and although the differences were not statistically significant, these patients tended to be younger (56 vs. 63 years, p=0.08) and have shorter intensive care unit stays (2.0 vs. 12.5 days, p=0.06). PTSS-positive and PTSS-negative groups did not differ significantly in prehospitalization neurological diagnoses (11% vs. 8%), psychiatric diagnoses (17% vs. 21%), and intensive care admission status (25% vs. 25%). More patients in the PTSS-positive group had returned to the emergency department (50% vs. 14%, p<0.01) and reported fatigue at follow-up (100% vs. 42%, p<0.001). In the multivariate logistic regression model, non-White race (OR=11, 95% CI=2-91) and returning to the emergency department (OR=19, 95% CI=3-252) were associated with PTSS-positive status., Conclusion: PTSS were twice as common among hospitalized COVID-19 survivors than among those in the general population., Competing Interests: Dr. Romano has received funding from Genentech. Dr. Sacco has received personal compensation from the American Heart Association for his role as editor-in-chief of Stroke. The other authors report no financial relationships with commercial interests.