Hardigan, Patrick C.

Background Stroke or Cerebrovascular Accident (CVA) is one of the leading causes of mortality in the world whether it be ischemic or hemorrhagic 1,2. There has been an association of increased incidence of stroke in patients with cancer due to multiple factors 3. Regarding hematologic malignancies, there have been studies to assess the risk of developing stroke in patients with Hodgkin lymphoma (HL), however the information on non-Hodgkin lymphoma (NHL) is limited and not well understood4. We conducted a retrospective case-control study to assess the incidence, risks, and complications and length of stay of patients with current or prior history of NHL who developed an ischemic stroke. Methods This case-control study identified 29,632 patients older than 18 years, with or without CVA and with or without active or history of Non-Hodgkin Lymphoma (NHL) who were admitted to diverse private hospitals between 2018-2022. The patients were divided into two groups, one with current or prior NHL (n=10,699) and a control group of patients (n=18,933) with similar characteristics. Patients with active hemorrhagic stroke, pregnancy, malignancies other than NHL, prior hemorrhagic or ischemic stroke, infective endocarditis, atrial fibrillation, and acute coronary syndrome on admission were excluded. We compared patient's characteristics and the risk of developing a stroke based on the presence or absence of NHL as well as the factors that increased hospital mortality. Length of stay was evaluated as a secondary outcome. Bivariate statistical analysis was used to calculate the odds ratios using RStudio 4.2.2 and JMP Pro 16.0 for all data analysis. Results Of the group with NHL 46.39 % (n=4958) were female, and 53.61% (n=5729) were male, 42% were current or former smokers (n=4497), 27.49% (n=2941) had diabetes, 44.68% (n=4780) had hypertension; 3.34% (357) of them passed away. Of the control group 57.51 % (n=10876) were female, and 42.49% (n=8036) were male, 35% were current or former smokers (n=6763), 16.43% (n=3111) had diabetes, 28.89% (n=5469) had hypertension; 0.47% (n=88) of them passed away. The mean length of stay of patients with stroke was 7.99 days in the NHL group, and 5.99 days in the control group. Regarding the admissions due to stroke, there were 214 patients in the group with NHL, and in the control group where there were 113. Patients with NHL are more likely to have a CVA compared to the control group (OR 2.39 p<0.0001 CI 1.47~3.85) Patients who have NHL are more likely to die (OR=6.08 p<0.001) CI 4.77~7.74) compared to patients without NHL from all causes. Conclusion Patients with Non-Hodgkin lymphoma have an increased risk of developing a stroke compared to patients with similar characteristics but without NHL (or other malignancies). It was also noted that patients had an increased length of stay. Other variables and characteristics of patients that were identified to be more likely to have a CVA and statistically significant for this sample are already well-known risk factors for CVA including diabetes, hypertension, and cardiovascular disease. However, this study aimed to isolate those variables to identify the risk for stroke in this unique population. Our study limitation is the broad spectrum of NHL and possible confounders between the different variants of NHL. More studies are needed to investigate this. References Navi B, Reiner A, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. J Am Coll Cardiol. 2017 Aug, 70 (8) 926-938. Turner, M., Murchie, P., Derby, S. et al. Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis. J Cancer Surviv 16, 1414-1448 (2022). https://doi.org/10.1007/s11764-021-01122-7 Dardiotis E, Aloizou AM, Markoula S, et al. Cancer-associated stroke: Pathophysiology, detection, and management (Review). Int J Oncol. 2019;54(3):779-796. doi:10.3892/ijo.2019.4669 Wei Y, Yang Q, Qin Q, et al. Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study. Eur Neurol. 2020;83(1):41-48. doi:10.1159/000506046

Abstract Under the influence of standard developmental physiology on the Earth’s surface (1 gravity equivalent known as “1G”), 70% of body fluids reside below the level of the heart.Fluid shifts towards the cephalic region during microgravity have also been speculated to contribute towards spaceflight associated neuro-ocular syndrome (SANS).Although a significant barrier to spaceflight, the underlying mechanism of SANS is not well understood, partially due to the spaceflight environment and limited medical capabilities including invasive diagnostic testing. Thus, non-invasive approaches to studying real-time fluid shifts in weightlessness could serve as critical areas of research to further SANS study and effective countermeasure protocol development. For continuous fluid shift monitoring and management, the goal is to establish baseline assessments utilizing real time point of care noninvasive imaging devices (NIID). NIID will first need to be quantified and validated through ground-based analogues, with subsequent acquisition of near continuous imaging from arrival in the weightlessness of LEO and during the time of adaptation, which may be variable among crew members. The purpose of this study was to examine temperature differential alterations, superficial venous flow patterns (head, neck, upper torso), and venous flow patterns along the lymphatic ventromedial bundles of the medial calves and thighs. Imaging was obtained in three different positions using three standards of care medical NIIDs: SnapShotTM by Kent Imaging, Scout by WoundVisionTM and LymphScannerTM by Delfin. 30 volunteers were assessed for temperature and lymphatic/venous flow using three different non-invasive devices that can measure temperature, perfusion, and image the lymphatic and venous structures. The volunteers were assessed in the sitting, supine, and 6-degree head down tilt (HDT) positions, with pre/post assessments for the HDT position. Venous and lymphatic flow patterns may vary upon position changes (sitting vs. supine vs. 6-degree head down tilt), and in response to MLD performance in the treatment group. Fifteen subjects per group (N = 30) completed all visits and were used in the full analysis. The sitting and supine position data did not show statistical significance at any of the time points and with the devices used. The HDT data from SnapShot (looking at perfusion, deoxy and oxyhemoglobin) and Wound Vision Scout (thermal imaging) did not show statistical significance between the control and treatment groups at any time points. No significant difference for any of the within-group comparisons were found with the Lymphscanner. A significant reduction in left temple TDC for the treatment group was found at post-30-minutes (5.77, 95% CI: 1.24, 10.30) and post-180-minutes. A significant reduction in right subclavicular TDC for the treatment group was found at post-180-Minutes (5.09, 95% CI: 0.16, 10.03). A significant increase in the left ventromedial bundle for the treatment group was found at post-90-Minutes (5.72, 95% CI: 0.34, 11.10) and post-120-Minutes (5.85, 95% CI: 0.47, 11.23). A significant increase in the right ventromedial bundle for the treatment group was found at post-90 minutes (5.53, 95% CI: 0.21, 10.84). This is the first HDT spaceflight analogue study, to our knowledge, in which dermal fluid shifts were evaluated using point-of-care noninvasive imaging modalities including Near Infrared Spectroscopy (NIRS), thermography and a subcutaneous edema monitor, with subsequent application of manual lymphatic drainage (MLD) techniques to stimulate dermal lymphatic function as a countermeasure and mitigation therapeutic for intervention in cephalad fluid shifts. Further validating studies are indicated for NIIDs to further quantify fluid shifts in both analogues and weightlessness.