Bostonia. Volume 15

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

Bostonia: The Boston University Alumni Magazine. Volume 4

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Integrating Climate Sensitive Design Principles in Municipal Processes : A Case Study of Edmonton’s Winter Patios

This paper explores winter patios in Edmonton through the lens of place and climate sensitive design, then reflects upon the existing regulations that influence the design and management of winter patios in Edmonton. The City of Edmonton provides this research opportunity because it is currently pursuing the creation of a four-season patio culture in the city, and has created a strong WinterCity agenda. The introduction explores Edmonton’s local climate and its winter city strategy. This is followed by an explanation of the study’s methodology. The purpose of this thesis is to study how climate sensitive design principles can be applied to create places that attract winter activity. The research questions ask how climate sensitive design principles are currently incorporated in patios, what barriers exist to creating these spaces, and how to overcome these barriers in municipal processes. Many cities in cold climates seek ways to create vibrant, active cities through all seasons, and this study explores how climate sensitive planning principles can help create environments that invite winter activity. To answer the research question, a qualitative methodology was used to examine the case study of Edmonton winter patios using Eliasson’s (2007) concept of place and microclimate. The study identifies design weaknesses in Edmonton patios with little provision of shelter from wind, snow and rain, as well as limited consideration of snow storage and removal. Interviews and document review identify lack of interest and a lack of attention to the physical component of place as barriers to the creation of winter patios. Finally, the use of analytical tools such as urban climatic maps are suggested, as well as the introduction of microclimate standards so information about weather and microclimate can influence how physical components of place are planned and evaluated

Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke

•Nilotinib, a treatment of CML, has been associated with cardiovascular events with preexisting risk factors and progressive intracranial atherosclerotic disease (ICAD).•We present a case of a patient on nilotinib, without any preexisting vascular risk factors, with acute left middle cerebral artery stroke in the setting of ICAD.•It is important to screen patients for ICAD, even without preexisting cardiovascular risk factors, prior to initiation of nilotinib.•Close monitoring for ICAD is warranted on maintenance therapy of nilotinib for stroke prevention. Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial

Misunderstanding the Female Athlete Triad: Refuting the IOC Consensus Statement on Relative Energy Deficiency in Sport (RED-S)

We are concerned that readers of the IOC paper will be confused and misled by the poorly referenced statements and frank (and sometimes dangerous) errors in the paper. The IOC authors should publish a correction of these and other errors noted. Broadening research of low energy availability in other groups, such as the male athlete, athletes of diverse ethnicities and the disabled athlete may help to advance science and may one day warrant introduction of a specific term for whatever serious clinical sequelae of energy deficiency may be discovered in future research on men. Research on the “Female Athlete Triad” has forged a platform from which a broad array of healthcare providers (e.g., physicians, sport dietitians, mental health professionals and athletic trainers) have made great strides in learning how to manage and treat affected women. Research on the “Female Athlete Triad” has also been translated to the lay public such that more and more affected female athletes and exercising women willingly seek education, prevention and treatment. Meanwhile, subsuming the term “Female Athlete Triad” under the umbrella of the term RED-S has the potential to confuse rather than enlighten, and undo decades of work educating and advocating for awareness, prevention and treatment for the Triad. The individual most impacted by the de-emphasis on the Triad will be the female athlete herself. The overwhelming clinical importance of the Female Athlete Triad compared with other conditions under the proposed RED-S umbrella will continue to make a specific reference for the Triad useful for those who deal with it, including physicians, coaches, sport dietitians, athletics trainers, parents and, most importantly, female athletes. As such, efforts promoting awareness, prevention and treatment of the Female Athlete Triad remain critically important and should not be overshadowed by an ill-conceived and poorly defended new construct

48. Internationale Kurzfilmtage Oberhausen = 48th International Short Film Festival

This catalogue for the 48th International Short Film Festival at Oberhausen contains short descriptions and biographies of the featured films and filmmakers, as well as information on the juries, prizes, competitions, and special programs. Curators and essayists provide texts on the theme of the special program, catastrophe, and selected filmmakers. Biographical notes

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America.

BackgroundTo analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome.MethodsMulticentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications.ResultsA total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age &gt;60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p&lt;0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome.ConclusionThere is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality