Intracranial Gliosarcoma: A National Cancer Database Survey of Clinical Predictors for Overall Survival.

OBJECTIVE: Gliosarcoma (GSM) is a variant of glioblastoma, 1 of the most common and aggressive primary brain tumors in adults. Our study seeks to analyze a large cohort of patients with GSM in the National Cancer Database (NCDB) to elucidate clinical predictors of overall survival (OS). METHODS: Data was collected on patients diagnosed with histologically-confirmed GSM using the NCDB (2004-2016). OS was determined via univariate Kaplan-Meier analysis. Bivariate and multivariate Cox proportional-hazards analyses were also utilized. RESULTS: Our cohort of 1015 patients had a median age at diagnosis of 61 years. Six hundred thirty-one (62.2%) were male, 896 (89.0%) were Caucasian, and 698 (68.8%) lacked any comorbidities. Median OS was 11.5 months. Regarding treatment, 264 (26.5%) patients underwent surgery (S) only (OS = 5.19 months), 61 (6.1%) underwent surgery and radiotherapy (S + RT) (OS = 6.87 months), 20 (2.0%) underwent surgery and chemotherapy (S + CT); (OS = 15.51 months), and 653 (65.4%) underwent S + CT + RT (triple) combination therapy (OS = 13.8 months). Notably, on bivariate analysis, S + CT (Hazard ratio [HR] = 0.59, P-value = 0.04) and triple therapy (HR = 0.57, P < 0.01) were associated with increased OS. S + RT was not significantly associated with OS. Similarly, on multivariate Cox proportional-hazards analyses, gross total resection (HR = 0.76, P = 0.02), S + CT (HR = 0.46, P < 0.01), and triple therapy (HR = 0.52, P < 0.01) predicted significantly increased OS. Furthermore, age >60 years old (HR = 1.03, P < 0.01) and the presence of comorbidities (HR = 1.43, P < 0.01) predicted significantly decreased OS. CONCLUSIONS: Despite maximal multimodal treatment, GSMs have poor median OS. NCDB data suggest age, comorbidities, extent of resection, and adjuvant treatment each minimally delays poor outcomes.

An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas.

How cone photoreceptors are formed during retinal development is only partially known. This is in part because we do not fully understand the gene regulatory network responsible for cone genesis. We reasoned that cis-regulatory elements (enhancers) active in nascent cones would be regulated by the same upstream network that controls cone formation. To dissect this network, we searched for enhancers active in developing cones. By electroporating enhancer-driven fluorescent reporter plasmids, we observed that a sequence within an intron of the cone-specific Pde6c gene acted as an enhancer in developing mouse cones. Similar fluorescent reporter plasmids were used to generate stable transgenic human induced pluripotent stem cells that were then grown into three-dimensional human retinal organoids. These organoids contained fluorescently labeled cones, demonstrating that the Pde6c enhancer was also active in human cones. We observed that enhancer activity was transient and labeled a minor population of developing rod photoreceptors in both mouse and human systems. This cone-enriched pattern argues that the Pde6c enhancer is activated in cells poised between rod and cone fates. Additionally, it suggests that the Pde6c enhancer is activated by the same regulatory network that selects or stabilizes cone fate choice. To further understand this regulatory network, we identified essential enhancer sequence regions through a series of mutagenesis experiments. This suggested that the Pde6c enhancer was regulated by transcription factor binding at five or more locations. Binding site predictions implicated transcription factor families known to control photoreceptor formation and families not previously associated with cone development. These results provide a framework for deciphering the gene regulatory network that controls cone genesis in both human and mouse systems. Our new transgenic human stem cell lines provide a tool for determining which cone developmental mechanisms are shared and distinct between mice and humans.

Clinical predictors of survival for patients with atypical teratoid/rhabdoid tumors.

PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). METHODS: Information was collected on patients with histologically confirmed AT/RT using the NCDB (2004-2016). Kaplan-Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional hazards (CPH) and logistic regression models. RESULTS: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7 ± 2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS = 5.91 months), 51 (27.7%) received surgery and chemotherapy (S + CT) (OS = 11.2 months), and 9 (4.89%) received surgery and radiotherapy (S + RT) (OS = 10.3 months). Forty-five (24.5%) received S + CT + RT combination therapy (OS = 45.4 months), 13 (17.1%) received S + CT + BMT/SCT (bone marrow or stem cell transplant) (OS = 55.5 months), and 16 (8.70%) received S + CT + RT + BMT/SCT (OS = 68.4 months). Bivariate analysis of dichotomized age (HR = 0.550, 95% CI [0.357, 0.847], p = 0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S + CT + RT, S + CT + BMT/SCT, or S + CT + RT + BMT/SCT combination therapy predicted significantly (p < 0.05) increased OS compared to surgery alone. CONCLUSION: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.

Assessing COVID-19 Health Information on Google Using the Quality Evaluation Scoring Tool (QUEST): Cross-sectional and Readability Analysis.

BACKGROUND: The COVID-19 pandemic spurred an increase in online information regarding disease spread and symptomatology. OBJECTIVE: Our purpose is to systematically assess the quality and readability of articles resulting from frequently Google-searched COVID-19 terms in the United States. METHODS: We used Google Trends to determine the 25 most commonly searched health-related phrases between February 29 and April 30, 2020. The first 30 search results for each term were collected, and articles were analyzed using the Quality Evaluation Scoring Tool (QUEST). Three raters scored each article in authorship, attribution, conflict of interest, currency, complementarity, and tone. A readability analysis was conducted. RESULTS: Exactly 709 articles were screened, and 195 fulfilled inclusion criteria. The mean article score was 18.4 (SD 2.6) of 28, with 7% (14/189) scoring in the top quartile. National news outlets published the largest share (70/189, 36%) of articles. Peer-reviewed journals attained the highest average QUEST score compared to national/regional news outlets, national/state government sites, and global health organizations (all P<.05). The average reading level was 11.7 (SD 1.9, range 5.4-16.9). Only 3 (1.6%) articles were written at the recommended sixth grade level. CONCLUSIONS: COVID-19-related articles are vastly varied in their attributes and levels of bias, and would benefit from revisions for increased readability.

High-Intensity Focused Ultrasound: A Review of Mechanisms and Clinical Applications.

High Intensity Focused Ultrasound (HIFU) is an emerging and increasingly useful modality in the treatment of cancer and other diseases. Although traditional use of ultrasound at lower frequencies has primarily been for diagnostic imaging purposes, the development of HIFU has allowed this particular modality to expand into therapeutic use. This non-invasive and acoustic method involves the use of a piezoelectric transducer to deliver high-energy pulses in a spatially coordinated manner, while minimizing damage to tissue outside the target area. This review describes the history of the development of diagnostic and therapeutic ultrasound and explores the biomedical applications utilizing HIFU technology including thermally ablative treatment, therapeutic delivery mechanisms, and neuromodulatory phenomena. The application of HIFU across various tumor types in multiple organ systems is explored in depth, with particular attention to successful models of HIFU in the treatment of various medical conditions. Basic mechanisms, preclinical models, previous clinical use, and ongoing clinical trials are comparatively discussed. Recent advances in HIFU across multiple medical fields reveal the growing importance of this biomedical technology for the care of patients and for the development of possible pathways for the future use of HIFU as a commonplace treatment modality.

Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.

BACKGROUND: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; P = .020) and body mass index (BMI) ≥25 kg/m2 (aHR, 0.37; 95% CI, 0.18-0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; P = .044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients.

BACKGROUND: Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m 2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

The Clinical Course of COVID-19 in the Outpatient Setting: A Prospective Cohort Study.

BACKGROUND: Outpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a prospective cohort study. METHODS: Outpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression. RESULTS: Among 118 SARS-CoV-2-infected outpatients, the median age (interquartile range [IQR]) was 56.0 (50.0-63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13-38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73-0.99). CONCLUSIONS: Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.