BACKGROUND: The coronavirus disease of 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020, with more than 187,000 deaths. An increasing body of evidence has supported central nervous system involvement.-METHODS: We conducted a review of the reported data for studies concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines.-RESULTS: Central nervous system manifestations range from vague nonfocal complaints to severe neurological impairment associated with encephalitis. It is unclear whether the neurological dysfunction results from direct viral injury or systemic disease. The virus could affect brainstem pathways that lead to indirect respiratory dysfunction, in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of the ongoing scientific and clinical findings.-CONCLUSIONS: The present review has consolidated the current body of data regarding the neurological impact of coronaviruses, discussed the reported neurological manifestations of COVID-19, and highlighted the recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons have also been provided.
It is well established that the tumor microenvironment plays an important role in cancer development and progression. The tumor microenvironment is composed of neoplastic cells, endothelial cells, pericytes, adipocytes, fibroblasts and other connective tissue cells, extracellular matrix components, multiple stem and progenitor cells, and a diverse array of innate and adaptive immune cells [Nat Rev Cancer 2007;7:139–147]. Understanding the mechanisms behind cell–cell communication in the tumor microenvironment is critical to understanding the drivers of tumorigenesis and metastasis. In this review, we discuss the interactions between adipose stem cells, a critical component of the tumor microenvironment, and various forms of cancer. Stem Cells 2019;37:1261–1266
Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These cells are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER+) breast cancer (BC) tumor growth and metastasis. In this study, we evaluate the effect of obASCs on ER+BC outside of the ERα signaling axis using breast cancer models with constitutively active ERα resulting from clinically relevant mutations (Y537S and D538G). We found that while obASCs promote tumor growth and proliferation, it occurs mostly through abrogated estrogen signaling when BC has constitutive ER activity. However, obASCs have a similar promotion of metastasis irrespective of ER status, demonstrating that obASC promotion of metastasis may not be completely estrogen dependent. We found that obASCs upregulate two genes in both ER wild type (WT) and ER mutant (MUT) BC: SERPINE1 and ABCB1. This study demonstrates that obASCs promote metastasis in ER WT and MUT xenografts and an ER MUT patient derived xenograft (PDX) model. However, obASCs promote tumor growth only in ER WT xenografts.
Purpose: The aim of this study is to further examine the associations of race, socioeconomic factors, and comorbidity with COVID-19 health outcomes. Methods: This is a retrospective cohort study of 309 PCR confirmed COVID-19 positive adults who presented to Tulane Medical Center in New Orleans, LA, from March 9 to May 29, 2020. The primary outcomes investigated were need for invasive mechanical ventilation (IMV) and in-hospital mortality. A multivariate analysis was performed to determine socioeconomic and medical risk factors for IMV and in-hospital mortality. Results: Compared to white patients, Black patients were more likely to present younger, female, obese, unemployed, and underinsured. However, when controlled for common risk factors, Black and white patients had similar risk for IMV and mortality. Increased age (≥65 years), obesity, and increased comorbidity were associated with increased risk for IMV and mortality. Conclusions: Race and socioeconomic factors may increase risk for COVID-19 infection but did not affect health outcomes within the hospital setting. Therefore, the higher rates of COVID-19 infection and mortality in vulnerable populations may be better explained by lower socioeconomic status, with subsequent higher comorbidity, in these populations. Community health initiatives should be prioritized in response to the COVID-19 pandemic.
Purpose In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.
Background: Steadily increasing expenditure in the United States health-care system has led to a shift toward a value-based model that focuses on quality of care and cost-effectiveness. Operations involving the spine rank among some of the most common and expensive procedures performed in operating rooms nationwide. Patient-reported outcomes measures (PROMs) are a useful tool for reporting levels of outcome and analyzing patient recovery but are both under-utilized and nonstandardized in spine surgery. Methods: We conducted a systematic review of the literature using the PubMed database, focusing on the most commonly utilized PROMs for spine disease as well as spinal deformity. The benefits and drawbacks of these PROMs were then summarized and compared. Results: Spine-specific PROMs were based on the class of disease. The most frequently utilized PROMs were the Neck Disability Index and the modified Japanese Orthopaedic Association scale; the Oswestry Disability Index and the Roland-Morris Disability Questionnaire; and the Scoliosis Research Society 22-item questionnaire (SRS-22) for cervicothoracic spine disease, lumbar spine disease, and spinal deformity, respectively. Conclusion: We found limited, though effective, use of PROMs targeting specific classes of disease within spine surgery. Therefore, we advocate for increased use of PROMs in spine surgery, in both the research and clinical settings. PROM usage can help physicians assess subjective outcomes in standard ways that can be compared across patients and institutions, more uniquely tailor treatment to individual patients, and engage patients in their own medical care.
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