Stony Brook University Hospital Research Articles

Educating and empowering health care teams who present to the hospital to recognize and intervene on cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients on bispecific t-cell engager therapy (BiTEs): A quality improvement study.

e23212 Background: Treatment of oncologic disease with Bispecific T-Cell Engager antibodies (BiTEs) are an emerging novel immunotherapy with demonstrated efficacy in multiple hematologic malignancies. Notable side effects of BiTE therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be life-threatening and must be rapidly identified. We aim to fill knowledge gaps surrounding CRS and ICANS for medical providers, particularly considering increased use of BiTE therapy. We hope that educating providers will allow faster recognition and treatment and will improve patient outcomes. Methods: Our study focused on the impact of educational presentations on awareness and identification of CRS/ICANS. Our intervention targeted the residents and attendings in the emergency department and the nurses, advanced practice providers, and hospitalists in the bone marrow transplant (BMT) unit at Stony Brook University Hospital. Anonymous surveys consisting of 9 multiple choice questions were conducted to assess baseline foundational knowledge of CRS/ICANS. QI consisted of a 15-minute educational presentation for both groups. The same surveys were repeated following the presentations to assess improvement in overall knowledge of CRS/ICANS. A two tailed independent T test was used to calculate significance. Results: The average pre-survey score for the emergency department (N = 37) was 39%. The average presurvey score for the BMT department (N = 13) was 45%. Significant improvements in scores after intervention were shown in both the emergency department (39% vs 66%, p = 0.0001) and the BMT department (45% vs 68%, p = 0.0006). Conclusions: Education among emergency department and hospitalist providers is essential in improving management of CRS and ICANS in patients treated with BiTEs. This quality improvement initiative confirmed a knowledge gap in CRS and ICANS amongst our healthcare teams. By providing educational resources to both departments, there was a significant improvement in this gap. Future directions for continued improvement in the detection and management of CRS/ICANS include patient medication identification cards, a central repository of treatment protocols, algorithms, and toxicities associated with BiTEs, and expanding our educational curriculum which are all currently under development at Stony Brook University Hospital.

Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.

e20591 Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p < 0.02). Decrease in CEA (p < 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p < 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]

Rogue AI: Cautionary Cases in Neuroradiology and What We Can Learn From Them.

Introduction In recent years, artificial intelligence (AI) in medical imaging has undergone unprecedented innovation and advancement, sparking a revolutionary transformation in healthcare. The field of radiology is particularly implicated, as clinical radiologists are expected to interpret an ever-increasing number of complex cases in record time. Machine learning software purchased by our institution is expected to help our radiologists come to a more prompt diagnosis by delivering point-of-care quantitative analysis of suspicious findings and streamlining clinical workflow. This paper explores AI's impact on neuroradiology, an area accounting for a substantial portion of recent radiology studies. We present a case series evaluating an AI software's performance in detecting neurovascular findings, highlighting five cases where AI interpretations differed from radiologists' assessments. Our study underscores common pitfalls of AI in the context of CT head angiograms, aiming to guide future AI algorithms. Methods We conducted a retrospective case series study at Stony Brook University Hospital, a large medical center in Stony Brook, New York, spanning from October 1, 2021 to December 31, 2021, analyzing 140 randomly sampled CT angiograms using AI software. This software assessed various neurovascular parameters, and AI findings were compared with neuroradiologists' interpretations. Five cases with divergent interpretations were selected for detailed analysis. Results Five representative cases in which AI findings were discordant with radiologists' interpretations are presented with diagnoses including diffuse anoxic ischemic injury, cortical laminar necrosis, colloid cyst, right superficial temporal artery-to-middle cerebral artery(STA-MCA) bypass, and subacute bilateral subdural hematomas. Discussion The errors identified in our case series expose AI's limitations in radiology. Our case series reveals that AI's incorrect interpretations can stem from complexities in pathology, challenges in distinguishing densities, inability to identify artifacts, identifying post-surgical changes in normal anatomy, sensitivity limitations, and insufficient pattern recognition. AI's potential for improvement lies in refining its algorithms to effectively recognize and differentiate pathologies. Incorporating more diverse training datasets, multimodal data, deep-reinforcement learning, clinical context, and real-time learning capabilities are some ways to improve AI's performance in the field of radiology. Conclusion Overall, it is apparent that AI applications in radiology have much room for improvement before becoming more widely integrated into clinical workflows. While AI demonstrates remarkable potential to aid in diagnosis and streamline workflows, our case series highlights common pitfalls that underscore the need for continuous improvement. By refining algorithms, incorporating diverse datasets, embracing multimodal information, and leveraging innovative machine learning strategies, AI's diagnostic accuracy can be significantly improved.

Implementation and mixed-methods evaluation of "Walk with a Doc" program at Stony Brook.

Walking groups run by trained individuals, lasting under an hour in a natural environment, may be a cost-effective way by which to encourage sustainable changes in physical activity as well as foster companionship and a shared experience of wellness among participants. Walk with a Doc (WWaD) is a national program that provides a platform for medical professionals, including physicians and medical students, to deliver a short talk on a health topic prior to walking side by side with patients and community members. To evaluate the WWaD Chapter at Stony Brook following implementation, a questionnaire was designed utilizing a mixed-methods approach (i.e.,containing qualitative and quantitative items) and administered to all attendees monthly prior to the health discussion. The aim of the questionnaire was fourfold: first, to obtain participant demographics; second, to obtain information on attendees' own perceptions of their health status and the role exercise plays in their health; third, to gain data on physical activity levels, including lengths of exercise sessions and types of activities performed; and fourth, to learn more about attendees' motivations and goals for participating in the walks. We received an IRB exemption. Physician and medical student volunteers were recruited from Stony Brook University Hospital, a suburban tertiary care center, to oversee program logistics. WWaD was scheduled to take place on the third Sunday of every month for 1 h at Heritage Park in Mount Sinai, New York. The event was advertised by volunteers to colleagues, peers, patients, and community members utilizing word of mouth, printed flyers, emails to listservs, and social media outlets. Each month, a physician volunteer oversaw a brief discussion (approximately 10 min in length). Over the course of the 5 month evaluation period, 91individuals participated in the walks, including repeat attendees. After excluding duplicate or incomplete entries, data from 30 participants were included in this analysis. The majority of participants were female (n=24) with a mean age of 50 years (range, 23-98 years). Feedback on WWaD program elements was largely positive. Participants commended the monthly speakers for "informative talks" (n=6) on "interesting topics" (n=4), with plans to review the supplemental information in educational pamphlets following the walk (n=4). The brochures were also deemed "helpful." Overwhelmingly, patients referred to the community gathering and team building aspects of WWaD as the "most enjoyable" aspect of the program (n=8) and a key driver for participation. This mixed-methods study of the WWaD chapter at Stony Brook contributes to a growing body of evidence highlighting the value of walking groups as effective avenues for collaboration in producing accessible healthy behavior.

Abstract TP164: Predisposing Factors and Outcomes of Primary Intracerebral Hemorrhage in Patients Presenting With Hyponatremia

Background: Hyponatremia is the most common electrolyte abnormality seen in intracerebral hemorrhage (ICH) and is associated with a nearly doubled mortality rate and more severe presentations. However, the current literature has not addressed what factors might predispose ICH patients to presenting with hyponatremia or developing it during their hospital stay. The aim of this study was to evaluate the characteristics, comorbidities, and inpatient outcomes prevalent amongst ICH patients with hyponatremia. Methods: A retrospective study was performed for 814 adult patients admitted from January 2011-December 2022 with primary ICH at Stony Brook University Hospital. We recorded sodium and serum chemistry levels throughout admission, medical history, radiographic hematoma volumes, and Modified Rankin Scale (MRS) and Glasgow Coma Scale (GCS) up to 1-year follow-up. Results: Hyponatremia on admission was seen in 79 (9.8%) patients. Another 311 patients (38.3%) developed hyponatremia during their hospital stay. Pre-existing hyponatremia was correlated with a history of diabetes while hyponatremia during stay was correlated with diabetes, liver disease, heavy drinking, and prior valve replacement. Complications such as pneumonia, UTI, or a bloodstream infection were more prevalent in patients with hyponatremia. They also had a longer hospital stay and higher inpatient mortality (χ2(1)=5.176, p=0.023). Patients with hyponatremia had significantly lower GCS values on discharge. A multivariate regression analysis of age, admission MRS, diabetes, liver disease, ICH score, volume, and minimum Na was statistically significant ( R 2=0.255, F(7,704)=34.46, p<0.001). Minimum Na reliably predicted death in this model (β=0.007, p=0.023). Conclusions: Several factors can predispose ICH patients to hyponatremia on presentation or be associated with developing hyponatremia during their hospital stay. This study showed that developing hyponatremia during the hospital stay was associated with worse outcomes at discharge. In addition, hyponatremia can significantly predict inpatient mortality when controlling for ICH severity and common aggravating factors.

Abstract B065: Biomarker approach to define tumor subtype in pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors with a predicted five-year survival rate in 2023 of 12%. Building on prior observations that molecular subtypes correlate with survival and response to treatment, our goal has been to understand the patterns of expression and prognostic correlations of three reciprocally expressed proteins previously identified as surrogate biomarkers of PDAC subtypes. Keratin 17 (K17) and Keratin 5 (K5) have both been identified as biomarkers of the basal subtype whereas GATA6, a transcription factor necessary for normal pancreatic development, is a surrogate marker of the classical subtype associated with longer-term survival. Here, we explore the expression of these three diagnostic biomarkers in PDAC and their specificity to tumor cells. Methods: Immunohistochemical analyses of K17 (KDx Diagnostics), GATA6 (R&D Systems), and KT5 (Leica) were performed on archival primary PDAC specimens from Stony Brook University Hospital (n= 30), by routine immunoperoxidase methods on serial sections. IHC stained slides were scanned using an Olympus VS200 slide scanner and images were imported into QuPath for digital analysis. Regions of interest (ROIs) were defined by the presence of tumor cells and were identified by histological assessment of representative sections. Digital scoring was performed on identified ROIs using the integrated "positive cell detection" function in QuPath and classified into three different stain intensities (1+, 2+, 3+). The threshold for each intensity is as follows: 1+, 0.2; 2+, 0.4; 3+, 1.0. According to the number of detections of each intensity, tumor cells were categorized into negative (0 and 1+) or positive (2+ and 3+). The percentage positive of analyzed biomarker expression within the tumor ROI was calculated by dividing the total number of positive cells by the total number of detected cells. Results: K17 was detected in both well and poorly differentiated PDAC components and in a few benign proliferative ducts of chronic pancreatitis but no staining was detected in stromal cells, benign ductal epithelium, or acinar cells. K5 was detected in a smaller proportion of cells from glandular components of the tumor as well as in most diffusely infiltrative single cells, benign ductal, and acinar cells but not in stromal cells. By contrast, GATA6 was detected in the nuclei of most cancer epithelial cells and was also detected in benign ductal cells, acinar cells, and stromal cells. The proportion of K17 expressing cells exceeded that of K5 positive cells in the great majority of ROIs and across cases. Conclusions: Keratin 17 detects a higher proportion of tumor cells than K5 and shows the lowest level of expression in benign cell types. By contrast, GATA6 IHC shows variable patterns of expression related to K17 or K5 expression and is expressed in the highest proportion of tumor cells, including both well-differentiated, diffusely infiltrative components, and benign tissue components. Citation Format: Carson Ho, Michael Horowitz, Lyanne Oblein, Shayan Sarkar, Soma Kobayashi, Karen Bai, Natalia Marchenko, Luisa Escobar-Hoyos, Kenneth Shroyer. Biomarker approach to define tumor subtype in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B065.

Abstract B041: Keratin 17 excludes CD8-positive T cells and recruits CD163-positive macrophages in pancreatic ductal adenocarcinoma

Abstract Background. Keratin 17 (K17) is a negative prognostic and predictive biomarker, overexpressed in the biologically most aggressive forms of pancreatic ductal adenocarcinoma (PDAC). In other anatomic sites and disease processes, K17 expression impacts the inflammatory microenvironment, correlating with changes in the expression of inflammatory cytokines and the infiltration of CD8+ T cells. Thus, we hypothesized that K17 expression also impacts the immune response in PDAC. Methods. We aimed to determine the relationship between intratumoral and peritumoral immune cell infiltrates versus K17 expression in tumor cells, using brightfield multiplexed immunohistochemistry (mIHC) and our suite of deep learning tools to quantitatively evaluate the expression of four biomarkers of T-cells and macrophages. The study included a multi-institutional cohort of 235 PDAC cases from Stony Brook University Hospital (n=54), Thomas Jefferson University (n=67), Cedars Sinai Medical Center (n=7) and Know Your Tumor PanCAN-Perthera (n=107). Peritumoral immune cells were scored in zones defined as stromal tissue within ≤25 µm of the closest tumor cell. Intratumor immune cells were defined as those that physically touched or overlapped with tumor cells. Immune cell counts in peritumoral and intratumoral K17-negatvie areas of the tumor were normalized to immune cell counts in K17-positive areas. Results. The density of CD8+ T cells in K17-negative peritumoral zones was greater than in K17-positive peritumoral zones in 82.6% of PDACs. Similarly, the density of intratumoral CD8+ T cells in K17-negative areas was greater than in K17-positive areas in 93.2% of cases. Less striking inverse correlations for immune cell density relative to K17 expression were found for CD4+ peritumor lymphocytes and both intratumoral and peritumor CD16+ macrophages. By contrast, CD163+ (tumor-promoting) macrophages were more numerous in K17+ peritumoral and intratumoral zones. All differences were statistically significant and independent of tumor grade, stage, histologic subtype, and neoadjuvant treatment history (p< 0.0001). Conclusions. Correlations between K17 and inflammatory cells suggests K17 expression negatively influences the number and infiltration of T-cells and contributes to the marked immunosuppressive effect of PDAC. These findings suggest that the biologic impact of K17 goes beyond its role as a negative prognostic biomarker that impacts tumor growth, metastasis, and chemoresistance, to suppress the immune response to PDAC. Understanding how K17 influences immune cell function may inform future immunotherapeutic opportunities for PDAC treatment. Citation Format: Lyanne Oblein, Sruthi Babu, Mariana Torrente-Goncalves, Lucia Roa, Michael Horowitz, Mahmudul Hasan, Danielle Fassler, Jaymie Oentoro, Emanuel Petricoin, Lynn M. Matrisian, Natalia Marchenko, Edik Blais, Felicia Allard, Ali Alkalin, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer. Keratin 17 excludes CD8-positive T cells and recruits CD163-positive macrophages in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B041.

Endotoxemia Correlates with Kidney Function and Length of Stay in Critically Ill Patients

Introduction: Endotoxin is a key driver of sepsis, which frequently causes acute kidney injury (AKI). However, endotoxins may also be found in non-bacteremic critically ill patients, likely from intestinal translocation. Preclinical models show that endotoxins can directly injure the kidneys, and in COVID-19 patients, endotoxemia correlated with AKI. We sought to determine correlations between endotoxemia and kidney and hospital outcomes in a broad group of critically ill patients. Methods: In this single-center, serial prospective study, 124 predominantly Caucasian adult patients were recruited within 48 h of admission to Stony Brook University Hospital Intensive Care Unit (ICU). Demographics, vital signs, laboratory data, and outcomes were collected. Circulating endotoxin was measured on days 1, 4, and 8 using the endotoxin activity assay (EAA). The association of EAA with outcomes was examined with EAA: (1) categorized as <0.6, ≥0.6, and nonresponders (NRs); and (2) used as a continuous variable. Results: Patients with EAA ≥0.6 had a higher prevalence of proteinuria, and lower arterial oxygen saturation (SaO₂) to fraction of inspired oxygen (FiO₂) (SaO₂/FiO₂) ratio versus patients with EAA <0.6. EAA levels positively correlated with serum creatinine (sCr) levels on day 1. Patients whose EAA level stayed ≥0.6 had a slower decline in sCr compared to those whose EAA started at ≥0.6 and subsequently declined. Patients with AKI stage 1 and EAA ≥0.6 on day 1 showed slower decline in sCr compared to patients with stage 1 AKI and EAA <0.6. EAA ≥0.6 and NR patients had longer hospital stay and delayed ICU discharge versus EAA <0.6. Conclusions: High EAA levels correlated with worse kidney function and outcomes. Patients whose EAA levels fell, and those with AKI stage I and day 1 EAA <0.6 recovered more quickly compared to those with EAA ≥0.6, suggesting that removal of circulating endotoxins may be beneficial in critically ill patients.

Bleeding Rectal Ulcer in an Elderly Veteran Receiving Pembrolizumab Therapy for Lung Cancer

From the ∗Stony Brook University Hospital, Stony Brook †Division of Infectious Disease, Northport Veteran Affairs, Northport, NY. Correspondence to: Alexander Njoroge, MD, Stony Brook University Hospital, 100 Nicolls Rd, Stony Brook, NY 11794. E-mail: [email protected]. The authors have no funding or conflicts of interest to disclose.

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms.

Cefiderocol is a novel cephalosporin recently approved by the FDA to aid clinicians in the fight against multidrug-resistant (including carbapenem-resistant) gram-negative organisms. The primary objective of this study is to evaluate the 14- and 28-day mortality associated with cefiderocol. We performed a retrospective chart review of all adult patients admitted at Stony Brook University Hospital between October 2020 and December 2021 and received cefiderocol for at least 3 days. Patients were excluded if they received more than one course of cefiderocol therapy or remained hospitalized at the time of this study. A total of 22 patients met the inclusion criteria. The all-cause mortality on day 28 for all patients was 13.6%, whereas this rate for patients with BSI was 0%, with cUTI was 0% and with LRTI was 16.7%. The all-cause mortality on day 28 for patients who received the dual antibiotics (in conjunction with cefiderocol) was 0%, compared to 25% for patients who only received cefiderocol (p = 0.25). We noted treatment failure in two patients (9.1%). Our findings suggest that cefiderocol could possibly be associated with lower all-cause mortality than previously thought. In our study, we did not find any significant difference between cefiderocol's use in combination with another antibacterial agent and its use as a monotherapy.

Initial mean arterial blood pressure (MABP) measurement is a risk factor for mortality in hypertensive COVID-19 positive hospitalized patients.

Hypertension (HTN) is associated with severe COVID-19 infection; however, it remains unknown if the level of blood pressure (BP) predicts mortality. We tested whether the initial BP in the emergency department of hospitalized patients portends mortality in COVID-19 positive(+) patients. Data from COVID-19(+) and negative (-) hospitalized patients at Stony Brook University Hospital from March to July 2020 were included. The initial mean arterial BPs (MABPs) were categorized into tertiles (T) of MABP (65-85 [T1], 86-97 [T2] and ≥98 [T3] mmHg). Differences were evaluated using univariable (t-tests, chi-squared) tests. Multivariable (MV) logistic regression analyses were computed to assess links between MABP and mortality in hypertensive COVID-19 patients. 1549 adults were diagnosed with COVID-19 (+) and 2577 tested negative (-). Mortality of COVID-19(+) was 4.4-fold greater than COVID-19(-) patients. Though HTN prevalance did not differ between COVID-19 groups, the presenting systolic BP, diastolic BP, and MABP were lower in the COVID-19(+) vs (-) cohort. When subjects were categorized into tertiles of MABP, T2 tertile of MABP had the lowest mortality and the T1 tertile of MABP had greatest mortality compared to T2; however, no difference in mortality was noted across tertiles of MABP in COVID-19 (-). MV analysis of COVID-19 (+) subjects exposed death as a risk factor for T1 MABP. Next, the mortality of those with a historic diagnosis of hypertension or normotension were studied. On MV analysis, T1 MABP, gender, age, and first respiratory rate correlated with mortality while lymphocyte count inversely correlated with death in hypertensive COVID-19 (+) patients while neither T1 nor T3 categories of MABP predicted death in non-hypertensives. Low-normal admitting MABP in COVID-19 (+) subjects with a historical diagnosis of HTN is associated with mortality and may assist in identifying those at greatest mortality risk.

Long term positional stability of the Argus II retinal prosthesis epiretinal implant

BackgroundThe Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, California) is an epiretinal prosthesis that serves to provide useful vision to people who are affected by retinal degenerative diseases such as retinitis pigmentosa (RP). The purpose of this study was to analyze postoperative movement of the electrode array.MethodsFive patients diagnosed with profound retinal dystrophy who have undergone implantation of retinal prosthesis at Stony Brook University Hospital. Fundoscopy was performed at postoperative month 1 (M1), month 3 (M3), month 6 (M6), month 12 (M12), and month 24 (M24) visits. Fundoscopy was extracted and analyzed via NIH ImageJ. Data analysis was completed using IBM SPSS. Various lengths and angles were measured each postoperative month using ImageJ.ResultsThere was no significant change in distance between the optic disc and the surgical handle (length AB) over the two-year span (F = 0.196, p = 0.705). There was a significant change in distance of length AB over time between patients between M3 and M6 (p = 0.025). A repeated measures ANOVA revealed that there was statistically significant change of the optic disc-tack-surgical handle angle (\U0001d6fe) (M1 to M24) (F = 3.527, p = 0.030). There was no significant change in angle \U0001d71f (the angle to the horizontal of the image), angle \U0001d736 (tack-optic disc-surgical handle), and angle \U0001d737 (optic-disc-surgical handle-tack).ConclusionOur results demonstrate that there may be postoperative movement of the retinal prosthesis over time, as a statistically significant downward rotation is reported over the 2 years span. It is important, moving forward, to further study this movement and to take into consideration such movement when designing retinal implants. It is important to note that this study is limited by the small sample size, and therefore, the conclusions drawn are limited.

Abstract WP15: Short-Term Functional Outcomes Of Patients With Large Vessel Occlusions Transported By Mobile Stroke Unit Compared To Conventional Transport.

Background: A major limiting factor of favorable outcomes among patients with emergent large vessel occlusions (ELVO) is delay in transfer to a comprehensive stroke center (CSC). Stony Brook University Hospital (SBUH) is one of two CSCs in Suffolk County, serving approximately 1.5 million patients over 912 square miles. In 2019, SBUH implemented 2 mobile stroke units in strategic locations within Suffolk County to facilitate rapid delivery of acute stroke treatments. With the capability of performing computed tomography angiography (CTA) in addition to non-contrasted head CT, SBUH MSU offers an opportunity to rapidly triage patients to necessary CSCs. We sought to compare functional outcomes of patients receiving thrombectomies following transport by MSU versus conventional EMS and hospital transfers. Methods: A retrospective study was conducted that included patients eligible to receive mechanical thrombectomy from 2017 to 2020. Patients who had pre-morbid modified Rankin scale (mRs) greater than 0, transient ischemic events, subarachnoid hemorrhage, intraparenchymal hemorrhage, or strokes post-hospital arrival were excluded. A total of 77 patients were included, 37 of whom received care by MSU and 40 by EMS or transfers. Time interval from Door-to-Needle time was measured. T-test for independent samples was used to measure differences in time among both groups. Functional outcomes were measured using mRS at discharge. Patients were trichotomized into three outcome groups, mRS 0-1, 2-4, and 5-6. Chi square was used to analyze differences among the outcome groups Results: MSU patients had a significantly shorter Door-to-Needle time than the EMS patients: (69± 64 min vs. 115 ± 65 min respectively, t=3.319, 78.155df, P&lt;0.001). At discharge in MSU group, 37.8% (14) had favorable mRS 0-1 compared to the control group 26.4% (14). The MSU group had 56.8% (21) moderate mRS 2-4 compared to the control group 47.2% (25) with mRS of 2-4. The MSU group had 5.4% (2) severe mRS 5-6 compared to the control group 26.4% (14). X 2 =7.716, 2df, p&lt;.01 Conclusions: CTA can be performed on MSUs to detect ELVOs in the field and achieve prompt triage of these patients to CSCs, thereby reducing time to thrombectomy and improving short-term functional outcomes.

Abstract WP44: Long Functional Outcomes After Acute Stroke Treatment After Implementation Of Mobile Stroke Unit Program

Background: Mobile stroke units (MSU) were developed as a tool to facilitate rapid delivery of acute stroke treatments and improving patient functional outcomes. Currently, there is limited data on the functional outcomes of patients receiving acute stroke treatments after being transported by MSU. In 2019, Stony Brook University Hospital (SBUH) implemented 2 mobile stroke units to assist with rapid delivery of acute stroke treatments. We sought to compare the long-term functional outcomes of patients who received acute stroke treatment after transport by our MSU versus conventional transportation prior to MSU implementation. Methods: This is a retrospective study of patients who received either tissue plasminogen activator (t-PA) and/or thrombectomy between the years 2017-2020 (n=316). Patients were separated into two groups; Either receiving care via MSU to SBUH (n=107) or receiving care after arrival/transfer to SBUH via conventional transportation (n=165). Time interval from door to t-PA administration and door to groin puncture were measured. T test for independent samples were used to measure differences in time among both groups. Long term functional outcomes were measured using modified Rankin Scale (mRS) at 90 days. Patients were trichotomized into three outcome groups, mRS 0-1, 2-4, and 5-6. Chi square was used to analyze differences among the outcome groups. Results: The MSU patients had a significantly shorter Door to TPA time than the control group: (28 min±22 min vs. 63 min ±40 min respectively, t=4.770, 74 df, P&lt;0.001). MSU patients had significantly shorter Door to groin puncture time than the control group (69 min ± 57 min vs 155min ± 271 min. respectively, t=2.807, 234 df, P&lt;0.001). In MSU group (44), 41% had favorable mRS 0-1 compared to control group 23% (31) with mRS of 0-1. MSU group had 36% (44) moderate mRS 2-4 compared to control group 45% (31) with mRS of 2-4. MSU group had 23% (41) severe mRS 5-6 compared to control group 33% (31). X 2 =9.770, 2df, p &lt;.01 Conclusions: MSU transported patients had shorter door to t-PA and thrombectomy times compared to patients using traditional EMS transfer system in Suffolk County. This improvement translated into more favorable long-term patient outcomes as seen with more MSU patients with lower 90 day mRS.

Abstract A010: Deciphering molecular and cellular differences between black and white colorectal cancers through in-depth transcriptomic analyses

Abstract Background Compared to all other racial groups, black Americans are most likely to be diagnosed with colorectal cancer (CRC) and are most likely to die from the disease. These racial disparities have been largely attributed to social and economic conditions that impact the prevalence of co-morbidities and access to quality health care. However, the molecular and cellular differences in CRC tumors between black and white subjects remain largely uncharacterized. Methods We analyzed paired tumor and adjacent normal RNA sequencing reads collected from 15 black and 18 white subjects at Downstate Medical Center and Stony Brook University Hospital (DSSBU). 273 additional RNA sequencing and clinicopathologic data from The Cancer Genome Atlas (TCGA) were used as a validation cohort. In the TCGA dataset, 54 black subjects were propensity score matched to 108 white subjects by age, sex, tumor location and tumor stage. Differential expression analysis was performed with EdgeR and Wilcoxon rank-sum test, which was recently recommended for human population samples. Gene Ontology (GO) enrichment analysis of DEGs (absolute log 2-fold change &amp;gt; 1, adjust p value &amp;lt; 0.05) was performed using enrichR. Gene set enrichment analysis (GSEA) of hallmark gene sets was applied to the gene list ranked by fold changes. The TPM (transcript per million) data was used to estimate relative cell abundance via xCell. Antitumor immune response likelihood scores were generated via the Estimate Systems Immune Response (EaSIeR) R package. Results EdgeR analysis identified 15 and 80 DEGs in the DSSBU and TCGA datasets, respectively. Two DEGs, CXCL10 and RPPH1 have decreased expression while EEF1A1P13 has higher expression in black samples from both datasets. CXCL10 remained a DEG under the Wilcoxon test in the TCGA dataset and in propensity score matched samples. GO enrichment analysis identified “Chemokine-mediated signaling pathway” as a significantly different biological process between tumor groups with a FDR of 0.043 and 0.0004 in TCGA and DSSBU respectively. GSEA computed a negative enrichment score for IL6 JAK STAT3 signaling, Interferon alpha response, Interferon gamma response, Allograft rejection and Myc targets V1 in the black group from both datasets. xCell analysis of the DSSBU data revealed significant enrichment for endothelial cells, adipocytes and hematopoietic stem cells in black tumor samples, while white samples were significantly enriched for basophils, T helper 2 cells and common lymphoid progenitor cells. No significant differences in cell type enrichment were identified in the TCGA dataset. Predicted immunotherapy response scores were not significantly different between races in both cohorts. Conclusion Our results show differences in genes and pathways associated with inflammation and immune cell recruitment which may impact anti-tumor activity. Our future work will include experimental validation of interesting genes accounting for the differences. Citation Format: Dimitri F. Joseph, Ellen Li, Bin Chen, Joseph F. LaComb, Alexandra Guillaume. Deciphering molecular and cellular differences between black and white colorectal cancers through in-depth transcriptomic analyses [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A010.

A mixed-methods program evaluation of the Alda Healthcare Experience- a program to improve healthcare team communication

BackgroundCommunication among interprofessional healthcare worker teams is critical to ensure a thriving and resilient workforce. We will evaluate the implementation and effectiveness of the Alda Healthcare Experience (AHE), a novel medical improvisation (improv) workshop designed to improve interprofessional communication skills among healthcare professionals. The AHE workshop includes a two-hour experiential training workshop led by an improv specialist and a clinical co-facilitator. In July 2022 we began implementing the AHE workshop by training 18 clinical co-facilitators who will co-facilitate the workshops for 550 healthcare workers from five hospital departments at Stony Brook University Hospital over the course of a year and a half. Using mixed-methods, we will conduct an Effectiveness-Implementation Hybrid Design project that includes an outcome evaluation (effectiveness) and a process evaluation (implementation).MethodsOur outcome evaluation will assess the impact of the AHE workshop on short- and long-term improvement in interprofessional communication, stress, and professional fulfillment. The process evaluation component will examine programmatic, organizational, and individual facilitators or barriers to effective implementation of the AHE workshop. Qualitative methods will include dimensional analysis employing individual interviews of 20–40 AHE Project Participants, 5–10 Selected Informants, and all the clinical co-facilitators. Quantitative methods will use a quasi-experimental longitudinal design with an intervention group and surveillance of a control group (wait-list) and repeated assessments using validated instruments measuring communications skills, professional fulfillment, stress, burnout, uncertainty tolerance, and teamwork.DiscussionEffective and efficient communication within healthcare teams is fundamental to building team cohesion that, in turn, supports individual resilience and builds positive organizational culture. The AHE program is an innovative approach to improve interprofessional healthcare communication and reduce healthcare worker burnout. In addition to institutional buy-in, rigorous evaluations of medical improv programs are necessary as a critical step in making such programs scalable.Trial registrationN/A

640. A Retrospective Assessment of the Effects of Cefiderocol in Patients with Multidrug-resistant Gram-negative Bacterial Infections

Abstract Background Cefiderocol has emerged recently as a new tool for combating multidrug-resistant bacterial infections; however, concerns about its efficacy has approved its FDA approval for the use in person with limited or no treatment options. The aim of our study is to assess the outcomes of patients treated with cefiderocol for such infections. Methods Retrospective cohort study which includes all adult patients who received cefiderocol for at least three days from 1 October 2020 to 31 December 2021 at Stony Brook University Hospital. Patients who received multiple courses of cefiderocol during the same hospitalization or are still hospitalized were excluded. Results 22 patients received cefiderocol and met the inclusion criteria. Average age, Charlson comorbidity index, and length of stay were 63.6 year, 5.4, and 53 days respectively. 6 patients had respiratory tract infections, 3 had bacteremia, 2 had complicated UTI, and 11 had infections in other sites. Bacteria isolates included Pseudomonas aeruginosa (14), Acinetobacter baumannii complex (8), and Stenotrophomonas maltophilia (1). The 14-day and 28-day all-cause mortality for all patients was 4.5% and 13.6%, respectively. The 14-day and 28-day all-cause mortality for patients with respiratory tract infections was 16.7% and 16.7%, bloodstream infections was 0% and 0%, complicated UTI was 0% and 0% and with infections at other sites was 0% and 15.4%, respectively. These rates are lower compared to CREDIBLE-CR study. The 28-day all-cause mortality in double gram-negative coverage group (including cefiderocol) was 0% versus 25% in the cefiderocol monotherapy group (p=0.25). The 28-day all-cause mortality in patient group with Pseudomonas aeruginosa was 14.3% vs. with Acinetobacter baumannii complex was 12.5%. Out of 18 isolates, 13 (72.2%) were susceptible to cefidericol, 1 (5.5%) was intermediate, and 4 (22.2%) were resistant. No carbapenemases were detected in any of the 11 tested clinical isolates of Pseudomonas aeruginosa. Treatment failure, defined as requiring change of antibiotic, was 9.1%. Conclusion The 14-day and 28-day all-cause mortality for all patients treated with cefiderocol are possibly lower than once thought to be. No significant differences were noted when cefidericol was used as monotherapy versus in combination. Disclosures Roderick Go, DO, Aptose Biosciences: Stocks/Bonds|Bristol Meyers Squibb: Stocks/Bonds|Cytodyn Inc.: Stocks/Bonds|Scynexis: Grant/Research Support.

507. Peripheral blood RNA signatures associated with human babesiosis, quality of life and neurological symptoms

Abstract Background Human babesiosis is an emerging tick-borne disease in the US that is primarily caused by the protozoan Babesia microti (Bm). Although Babesiosis can cause life-threatening infections, the pathophysiology including host and parasite determinants associated with disease severity are largely unknown. The aim of this study is to identify parasite and host signatures of human babesiosis and correlate these with disease severity and long-term symptoms. Methods We enrolled prospectively patients with acute babesiosis (microcopy positive blood smear for Bm, confirmed by PCR) at Stony Brook University Hospital during 2020-2021. Blood samples and surveys were completed at initial diagnosis (Visit=1;V1) and at months 1, 6 and 12 (V2,V3,V4). Total RNA from whole peripheral blood was isolated using the PAXgene Blood RNA Kit from individuals infected with Bm and healthy controls. Quality of life (QOL) surveys were administered to patients. Results Peripheral blood transcriptome analysis of 17 patients (median age: 63 years, range 42-78; 24% female) who presented with babesiosis were distinctly different from uninfected individuals (n=9). Babesiosis was associated with a peripheral blood Type I and Type II Interferon transcriptional signature. Other dominant transcriptional signatures included those involved in activation of mononuclear cells, oxidative phosphorylation, inducible nitric oxide synthase and regulation of homeostasis as well as inducible nitric oxide synthase. Ingenuity Pathway Analysis for clinical chemistry and hematology also highlight changes associated with cardiotoxicity, hepatotoxicity, and nephrotoxicity as well as increased levels of red blood cells. Patients with babesiosis showed a persistent deterioration of QOL in cognition [mean V1=33.1; V3=36.3] and satisfaction [mean V1=28.4; V3=34]. Also a decrease in QOL over time despite effective treatment [mean at V1 82 (SD: 5.9), V2 80 (8.1), V3 76 (4.7) (p &amp;gt;0.05). Heat Map Summary. Volcano Plot Gene Pathways Analysis Conclusion Babesiosis is associated with a marked alteration in the peripheral blood transcriptome of patients that may also provide insight into both the pathophysiology of the disease including severity and complications. Furthermore, even after successful treatment, babesiosis may result in long-term impacts on quality of life indicators. Disclosures All Authors: No reported disclosures.

367. Procalcitonin as a Potential Biomarker in the Study of Human Babesiosis

Abstract Background Procalcitonin (Pct) has been gaining momentum as a potential biomarker during parasitic infections as studies have demonstrated that Pct levels are significantly elevated during certain forms of protozoal sepsis. Given this, the goal of this pilot study is to determine the relationship between Pct levels and parasitemia (Par) during infection with Babesia microti and to elucidate the potential for Pct to be used as a biomarker in the study of babesiosis. Methods Babesia cases were collected from Stony Brook University Hospital (SBUH) and South Hampton Hospital (SHH) from 2012 to 2019. Median values of maximum Par and Pct throughout hospitalization were recorded and cases were referenced for admission to the intensive care unit (ICU). Correlation between maximum Par and Pct values were examined with the nonparametric Spearman rank correlation and fractional polynomials were used to assess the functional form of the correlation. Receiver-operator characteristic (ROC) curve analyses were used to identify cutoff points for Pct and maximum Par as markers for prediction of ICU admission. Results A total of 33 patients met the inclusion criteria for acute babesiosis. In fractional polynomial analysis, log-transformed Pct levels had a linear correlation with log-transformed maximum Par, r=0.556 (P=0.001, Fig 1A). In ROC curve analysis, a cut off level of ≥ 1.2 ng/mL for Pct had optimal prediction characteristics for ICU admission (sensitivity 62.5%, specificity 88%; correct classification 82%) with a relevant AUC of 0.77 (95% CI: 0.58–0.89; P=0.005, Fig 1B). A cut off level of ≥ 3.6% for maximum Par had optimal prediction characteristics for ICU admission (sensitivity 75%, specificity 92%, correct classification 88%) with a relevant AUC of 0.75 (95% CI 0.58—0.89; P= 0.005, Fig 1B). Comparison of AUC for Pct and Par yielded no significant difference (P=0.8). Figure 1A. Linear correlation between log10-parasitemia and log10- procalcitonin levels. The linear correlation of the log-transformed variables was r=0.556 (P=0.001), similar to the nonparametric (Spearman) correlation coefficient (ρ=0.567). The red dots represent patients who were admitted to the intensive care unit. Figure 1B. Receiver-operator characteristic curve of parasitemia for prediction of intensive care unit admission (0.75; 95%CI: 0.58—0.89; P=0.005); optimal cut-off is 3.6%. Receiver-operator characteristic curve of procalcitonin for prediction of intensive care unit admission (C=0.77; 95%CI: 0.58–0.89; P=0.005); optimal cut-off is 1.2 ng/mL. Conclusion Our analysis demonstrated a positive linear correlation between Pct and maximum Par, which is the current standard marker for severe disease. Also, our ROC analyses estimate that Pct values ≥ 1.2 ng/mL and Par ≥ 3.6% suggests severe disease and need for ICU admission (Fig 1A, 1B). Given this, our findings suggest that Pct may have potential for predicting severe disease during babesiosis. Disclosures All Authors: No reported disclosures.

1106. A Retrospective Assessment of the Effects of Baricitinib and Tocilizumab on COVID-19 Patients requiring High Flow Oxygen

Abstract Background SARS-CoV-2 has been a leading cause of mortality worldwide for over two years. It continues to be a group effort to discover treatment to prevent further deterioration during the disease course. Positive outcomes have been observed in select patients with immune modulator therapy. Although large randomized controlled trials have investigated the use of immunomodulators in COVID-19 therapy, few have compared the differences in safety profiles and clinical outcomes between the different drugs. We studied the differences in outcomes in hospitalized patients with COVID-19 pneumonia treated with baricitinib versus tocilizumab. Methods Adult patients admitted to Stony Brook University Hospital between April 2020 and April 2021 with high flow oxygen requirements due to severe COVID-19 pneumonia were retrospectively analyzed. The primary endpoint was the time to reduction of highest oxygen requirement 14 days after immune modulator therapy was administered or hospital discharge, whichever came first. Secondary endpoints include length of hospital stay (LOS), 28-day mortality, and serious adverse events. Results 132 patients with COVID-19 pneumonia were treated with immune modulators. One patient was excluded from primary and secondary analysis due to having received both tocilizumab and baricitinib. All patients received steroids and remdesivir. 73 received baricitinib and 58 received tocilizumab. Oxygen requirements at the initiation of either baricitnib or tocilizumab had a mean of 5.84±0.6 and 5.9±0.7, respectively using the WHO ordinal scale. The mean time to oxygen down titration in the baricitinib group was similar (5.7±2.6 and 6.07±2.7 days). In continuous variable analysis, patients who received baricitinib had a longer duration of fever (6.0 days vs 3.6 days, p=0.04) and lower serum ferritin (909.9 ng/ml vs. 1331.8 ng/ml, p=0.09). LOS was not similar between the groups (mean 24.4 vs. 25.8, p=0.89). Hospital mortality was not statistically significant between the two groups (32.9% vs. 27.6%, p=0.514). Conclusion This study suggests similar outcomes for oxygen requirements, hospital length of stay, and mortality between baricitinib and tocilizumab when given in conjunction with remdesivir and steroids for severe COVID-19 pneumonia. Disclosures Kathy Tin, D.O., Merck: Stocks/Bonds|Novavax: Stocks/Bonds|Pfizer: Stocks/Bonds Roderick Go, DO, Aptose Biosciences: Stocks/Bonds|Bristol Meyers Squibb: Stocks/Bonds|Cytodyn Inc.: Stocks/Bonds|Scynexis: Grant/Research Support.