Telemedicine Use Among Physiatrists During the Early Phase of the COVID-19 Pandemic and Potential for Future Use.

Introduction: With the coronavirus disease 2019 (COVID-19) pandemic causing the need for social distancing, telemedicine saw a significant increase in use to provide routine medical care. As a field, physiatry had already been implementing telemedicine prior to the pandemic. In this study, we characterized the use of telemedicine among physiatrists during the early phase of the COVID-19 pandemic to understand the barriers and facilitators to implementing telemedicine use in the field of physiatry in the future. Methods: Online survey of a cross-sectional sample of physiatrists. Analysis was conducted using logistic regression. Results: One hundred seventy one (n = 171) participants completed the survey. Before the pandemic, only 17.5% of respondents used telemedicine. In the logistic regression, physicians who used a hospital-provided platform were more likely to use telemedicine in the future compared with those who used their own secure platform, conducted a phone visit, and used a non-secure platform or other platforms. The three most popular barriers identified were "inability to complete the physical examination," "patients lack of access to technology," and "patients lack of familiarity with the technology." Discussion: Focus on education on telemedicine functional examination strategies and technology strategies for patients and providers (including addressing the digital divide and hospital-provided secure platforms) are potential targets of implementation strategies for greater telemedicine uptake for physiatrists in the future.

Pain and Addiction: The Distribution of Supply and Demand During the Opioid Epidemic.

ABSTRACT: A considerable portion of the opioid epidemic has been driven by physician-prescribed opioids for pain management. Thus, policies to address the epidemic must consider not only the resources available to manage addiction but those to manage acute and chronic pain as well. For the period 2017 to 2019, the authors sought to describe the distribution, by state, of indicators of the supply of resources to address pain and addiction (graduate medical education subspecialty training in pain and addiction, number of board-certified pain and addiction specialists, number of opioid treatment centers), as well as indicators of the demands for those services (opioid prescriptions, opioid overdose deaths), to identify states that seem to suffer from a mismatch between supply and demand. It was also sought to examine the relationships between these treatment resources and indicators of the magnitude of the opioid epidemic, through an exploratory correlational analysis. The resulting model may inform public policy by suggesting areas in need of greater graduate medical education training and more pain and addiction specialists and by suggesting hypotheses about the impact of these specialists on outcome that are worthy of further study.

Central Visual Oscillopsia: Case Report and Review of the Literature.

Here we present a patient with persistent central visual oscillopsia, review the literature on this condition, and report results from an experimental intervention using repetitive transcranial magnetic stimulation. A 57-year-old man reported persistent visual oscillopsia after a traumatic brain injury suffered 20 years earlier. Symptoms were presumed to be of cortical origin given his normal eye movements, eye stability, and peripheral vestibular function. Furthermore, he reported oscillopsia with visual imagery during eye closure. Occipital lesions damaging white matter connections identified on magnetic resonance imaging were suspected to be the cause of his symptoms. Repetitive transcranial magnetic stimulation was applied to the left extrastriate visual motion area V5/MT, to bilateral V5/MT, and to bilateral striate visual area V1. The primary outcome measure was dynamic visual acuity. Secondary outcome measures were gaze stabilization testing and subjective improvement as noted by interviews of the patient. Gaze stabilization and dynamic visual acuity testing revealed no difference between pre- and post-intervention with repetitive transcranial magnetic stimulation. The patient reported symptomatic improvement in large-amplitude oscillations that persisted for at least 12 months, but stated that smaller-amplitude oscillations were unchanged. Pathologies associated with central oscillopsia in the literature include neuromyelitis optica spectrum disorder, stroke, migraine without infarction, and psychological trauma. The patient's reported improvement in large- but not small-amplitude oscillopsia suggests that these symptoms may result from different neurophysiological mechanisms. Repetitive transcranial magnetic stimulation did not result in clinically significant improvement, suggesting a need for other strategies to treat this condition.

Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells.

The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based cytoprotective mechanism acting to prevent pathologies accompanying protein aggregation. It is frequently active in tumors, but relatively unstudied in gliomas. We hypothesized that UPR stress effects on glioma cells might protect tumors from additional exogenous stress (ie, chemotherapeutics), postulating that protection was concurrent with altered tumor cell metabolism. Using human brain tumor cell lines, xenograft tumors, human samples and gene expression databases, we determined molecular features of glioma cell UPR induction/activation, and here report a detailed analysis of UPR transcriptional/translational/metabolic responses. Immunohistochemistry, Western and Northern blots identified elevated levels of UPR transcription factors and downstream ER chaperone targets in gliomas. Microarray profiling revealed distinct regulation of stress responses between xenograft tumors and parent cell lines, with gene ontology and network analyses linking gene expression to cell survival and metabolic processes. Human glioma samples were examined for levels of the ER chaperone GRP94 by immunohistochemistry and for other UPR components by Western blotting. Gene and protein expression data from patient gliomas correlated poor patient prognoses with increased expression of ER chaperones, UPR target genes, and metabolic enzymes (glycolysis and lipogenesis). NMR-based metabolomic studies revealed increased metabolic outputs in glucose uptake with elevated glycolytic activity as well as increased phospholipid turnover. Elevated levels of amino acids, antioxidants, and cholesterol were also evident upon UPR stress; in particular, recurrent tumors had overall higher lipid outputs and elevated specific UPR arms. Clonogenicity studies following temozolomide treatment of stressed or unstressed cells demonstrated UPR-induced chemoresistance. Our data characterize the UPR in glioma cells and human tumors, and link the UPR to chemoresistance possibly via enhanced metabolism. Given the role of the UPR in the balance between cell survival and apoptosis, targeting the UPR and/or controlling metabolic activity may prove beneficial for malignant glioma therapeutics.

Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine.

PURPOSE: This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. Ultrasound-guided fine needle aspirate detected primary bronchoalveolar adenocarcinoma, verified via computed tomography, with a second smaller nodule discovered in the right cranial lung lobe. MATERIALS AND METHODS: A lateral thoracotomy with right cranial lung lobectomy was performed. Histopathological analysis of the nodules and an excised lymph node identified grade III bronchoalveolar adenocarcinoma with vascular infiltration and lymph node metastasis - a grim diagnosis with a reported median survival time of 6-27 days. A 10-g sample of the tumour was processed into a chaperone-rich cell lysate (CRCL) vaccine, which was administered weekly to the patient. Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was applied topically for the first 12 treatments to stimulate local Langerhans cells. A single injection of bacillus Calmette-Guerin (BCG) was administered for additional immune stimulation at week 30 of treatment. RESULTS: The dog remained stable and in otherwise good health until diffuse relapse occurred 44 weeks after the initial treatment; following gastrointestinal bleeding, the dog was euthanised 50+ weeks post diagnosis. CONCLUSION: To the authors' knowledge, this is the first report of significantly prolonged survival following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine patient. This case report suggests that CRCL vaccine combined with topical imiquimod is a safe, effective treatment for canine tumours.

Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles.

Medulloblastomas are the most prevalent malignant pediatric brain tumors. Survival for these patients has remained largely the same for approximately 20 years, and our therapies for these cancers cause significant health, cognitive, behavioral and developmental sequelae for those who survive the tumor and their treatments. We obviously need a better understanding of the biology of these tumors, particularly with regard to their migratory/invasive behaviors, their proliferative propensity, and their abilities to deflect immune responses. Exosomes, virus-sized membrane vesicles released extracellularly from cells after formation in, and transit thru, the endosomal pathway, may play roles in medulloblastoma pathogenesis but are as yet unstudied in this disease. Here we characterized exosomes from a medulloblastoma cell line with biochemical and proteomic analyses, and included characterization of patient serum exosomes. Further scrutiny of the proteomic data suggested functional properties of the exosomes that are relevant to medulloblastoma tumor biology, including their roles as proliferation stimulants, their activities as attractants for tumor cell migration, and their immune modulatory impacts on lymphocytes. Aspects of this held true for exosomes from other medulloblastoma cell lines as well. Additionally, pathway analyses suggested a possible role for the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A); however, inhibition of the protein's activity actually increased D283MED cell proliferation/clonogenecity, suggesting that HNF4A may act as a tumor suppressor in this cell line. Our work demonstrates that relevant functional properties of exosomes may be derived from appropriate proteomic analyses, which translate into mechanisms of tumor pathophysiology harbored in these extracellular vesicles.