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A previously independent 82-year-old woman presented with 5 months of worsening confusion, mobility and cognitive decline, with deficits in orientation, language and executive function. A cerebral dural arteriovenous fistula was identified and successfully embolised, after which her cognitive ability and independence dramatically improved. Although rare, a dural arteriovenous fistula may mimic a rapidly progressive dementia, but its early recognition and treatment can completely reverse the dementia.

Background The efficacy of an extended-release injectable moxidectin (0.5 mg/kg) suspension (ProHeart® 12) (PH 12) in preventing the development of Dirofilaria immitis in dogs for 12 months was investigated in laboratory and field studies in the USA. Methods In each of two laboratory studies, 20 dogs ≥ 12 months of age were randomly allocated to receive a subcutaneous injection of saline or PH 12 on Day 0 and were then inoculated with 50 D. immitis third-stage larvae (L3) on Day 365. All dogs were necropsied ~ 5 months post-inoculation for adult worm counts. The field efficacy study included dogs ≥ 10 months of age from 19 veterinary clinics in the USA treated with either 20 monthly doses of Heartgard® Plus (HG Plus) (296 dogs) or two doses of PH 12 (297 dogs) on Days 0 and 365. Efficacy was determined on Days 365, 480 and 605 using adult HW antigen and microfilaria testing to assess adult HW infection. Results PH 12 was 100% effective in preventing HW disease in all three of these studies. In the laboratory studies, no PH 12-treated dogs had any adult HWs, whereas all control dogs in both studies had adult HWs [geometric mean, 30.2 (range, 22–37) for Study 1 and 32.6 (22–44) for Study 2]. In the field study, all dogs treated with PH 12 tested negative for adult HW infection on all test days (Days, 365, 480 and 605), whereas four dogs receiving HG Plus (positive control) tested positive for HWs during the study (three dogs on Day 365 and one dog on Day 480). All four dogs treated with HG Plus that subsequently tested positive for HWs during the field study were from the lower Mississippi River Valley region, where HW resistance to macrocyclic lactone preventives has been confirmed to occur. PH 12 was significantly better than HG Plus in preventing heartworm disease in the field study (P = 0.0367). PH 12 was well-tolerated in both laboratory and field studies. Conclusions A single dose of ProHeart® 12 was 100% effective in preventing heartworm disease in dogs for a full year in both laboratory and field studies.

Background:Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.Methods:During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.Findings:The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation:To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding: None.

Introduction: The ability to model the microenvironment of primary and secondary tumor sites is critical for advancing treatment options for metastatic breast cancer. There are currently no 3D tumor models that mimic the in vivo vascular geometry and tumor microenvironment for monitoring extravasation, tissue invasion, and colonization of secondary sites by metastatic tumors. In this study, we report on the development of a 3D tumor model with primary and secondary tumor sites, where metastatic breast cancer cells can escape the primary site, circulate in circulation, adhere to the vascular endothelium and subsequently invade distant tissues. Materials and Methods: Multiple synthetic tumor networks comprising primary and secondary tumor sites were developed using in vivo images and fabricated using soft lithography. Fluorescent dyes (FITC-dextran) was used to test the fluidic integrity while nano and micro-particles were used to test the porosity of the developed devices. Primary vascular endothelial cells were cultured in the vascular channels while GFP-labeled metastatic human breast cancer cell line (MDA-MB-231/GFP) or non-metastatic (MCF-7/GFP) was cultured in the primary tumor site in a 3D environment using Matrigel™. The vascular networks were perfused with endothelial cell media under physiological fluid flow conditions. Real-time monitoring of cellular growth, extravasation and invasion was performed using fluorescence microscopy over a four week period. Results and Discussion: Metastatic MDA-MB-231 breast cancer cells proliferated rapidly in the primary tumor site in contrast to non-metastatic MCF-7. Tumor cells were found to initiate a metastatic cascade as early as 7-10 days following growth in the primary site comprising of intravasation into the vascular channels, rolling and adhesion on the endothelium and extravasation into the secondary site. Significant differences were observed on the tumor behavior based on the flow profiles and morphology of the vascular networks. These results provide a unique perspective of the in vivo realism in an in vitro system for monitoring metastasis Conclusions: We have developed a 3D vascularized model for monitoring the invasive growth and the metastatic potential of tumors thereby mimicking the in vivo microenvironment of solid tumors. This model can be used to investigate tumor-endothelial cell interactions using a combination of real-time imaging techniques and screening of targeted therapeutics that may reduce the metastatic potential of tumors. Citation Format: Deborah Ramsey, Dustin Haithcock, Charles Garson, Ashley Gilbert, Ketan Bhatt, Balabhaskar Prabhakarpandian, Kapil Pant. 3D microfluidic tumor model for investigating metastatic tumor migration and colonization of secondary sites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-035.