Ohio State University Medical Center Research Articles

Apples

This piece is a picture of an engraving on the Spirit of Women Park located outside at the center of The Ohio State University Medical Center, followed by a creative nonfiction piece. Both the visual and text illustrate the ways that disability and place intersect with family through naming (including: diagnosis, colloquialisms, and importantly, family names). Taking a feminist stance, this personal depiction focuses on the ways that names have meaning through generations and families, especially in a setting where language often revolves around cure. Influenced by the work of Eli Clare, this piece brings into the forefront the way families are both challenged by and challenge hospital systems, as names are reclaimed, given, and identified both within the family, and within the Spirit of Women Park. In particular, disability identification is reclaimed.

Methylome Analysis of Epstein-Barr Virus with Nanopore Sequencing Reveals Viral State Dynamics

Epstein Barr Virus (EBV) is a gammaherpesvirus responsible for a broad spectrum of human diseases, including hematologic malignancies and autoimmune disorders. EBV maintains lifelong infection by entering an endosomal state of latency inside its host cell. In response to external stimuli EBV undergoes lytic activation, resulting in vast gene expression changes, DNA replication, and eventually release of infectious viral particles. DNA methylation of the EBV genome is essential to regulating its life cycle. Both lytic and latent life stages are key determinants of EBV-driven disease, but current clinical assays for EBV are limited to detecting the presence of EBV and do not provide important information on EBV lytic state. Thus, making clinical decisions based on EBV detection alone has remained challenging. To address these limitations, we have developed an EBV analysis pipeline utilizing nanopore sequencing from amplification-free, native DNA that directly interrogates CpG dinucleotide DNA methylation on the EBV genome. Our workflow generates highly accurate EBV methylation calls for the majority of CpGs across the EBV genome. We also deployed a quantitative mass-spectrometry-based methylation assay (EpiTYPER) to validate our data and provide broader analysis of a representative subset of methylation sites (n=123 methylation sites from n=25 EBV loci). To initially investigate the relationship between locus-specific EBV DNA methylation and EBV gene expression, we compared DNA methylation and RNA sequencing profiles in EBV-positive cell lines (n=7). We correlated global EBV DNA methylation levels and the overall patterns of latent versus lytic EBV gene expression. We found that average methylation levels are related to the ratio of latent versus lytic gene expression, establishing nanopore-derived DNA methylation as a method to quantify latent and lytic states in a given sample. We next shifted our approach to bin nanopore reads based on the average methylation of all CpGs per read, hypothesizing that latent/lytic viral states derive from distinct subpopulations of EBV endosomes that contain methylated versus unmethylated DNA. We uncovered widespread co-occurrence of high and low methylated viral DNA in cell lines, indicating that EBV methylation states exist in defined subfractions with either present or absent DNA methylation. In cell models of latent EBV infection (Akata, Kem, MEC1, Mutu, Rael) this approach showed that methylation states dynamically responded to lytic induction and selective pressure via antiviral treatment with ganciclovir. Of note, we observed a shift in methylation without the appearance of partially methylated DNA, indicating that EBV lytic activation/replication is associated with the appearance of unmethylated EBV DNA, and not gradual demethylation of endosomes in the latent viral state. Finally, we aimed to obtain measurements of overall EBV status in patients, using nanopore sequencing of cell-free DNA (cfDNA) obtained from patient plasma. We analyzed patients diagnosed with different EBV-positive diseases from The Ohio State University Medical Center, including n=3 patients with lymphomas (Burkitt, plasmablastic and diffuse large B cell lymphoma) and n=2 patients with post-transplant lymphoproliferative disorder (PTLD). The patient samples with lymphoma displayed a near uniformly high methylation profile, with little evidence of unmethylated DNA/lytic replication. One of the PTLD patients analyzed showed a distinct bi-modal distribution of per read EBV methylation values, indicating the presence of lytic replication in a significant proportion of cells. In conclusion, nanopore sequencing analysis of methylated versus unmethylated EBV DNA subfractions is a quantitative method for determining viral states. In patient samples, nanopore sequencing revealed methylation heterogeneity in cfDNA and may be a useful advancement compared to standard clinical EBV detection. Quantifying the relative ratio of latent versus lytic virus in a liquid biopsy sample could be used to guide therapy selection for patients displaying EBV-positivity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract P2097: Hypochloremia Alters Cardiac Physiology After Myocardial Ischemia-Reperfusion Injury

Ischemic heart disease (IHD) is one of the leading causes of death related due to heart failure (HF). It is mainly characterized by impairment of heart contraction-relaxation (rhythmicity) and cardiac output. While a myriad of cellular processes is associated with IHD, one of the major cellular aspects strongly associated is the electrolyte and ionic imbalance. Serum sodium levels have been a well-established adverse prognostic marker for patients with chronic heart failure. Recent evidences have suggested that the lower serum chloride (hypochloremia, &lt90mM) is associated with increased mortality risk in patients with chronic HF independent of serum sodium levels. Serum chloride (Cl - ) is a major anion in physiology but its correlation to IHD has not been studied extensively. Hence, to better understand the role of hypochloremia in HF patients, we reviewed patients who received a left ventricular assist device (LVAD) placement at The Ohio State University Medical Center. Survival analysis demonstrated that patients with hypochloremia before LVAD placement had decreased survival at one year compared to patients with normal serum Cl - (p=0.0055). Moreover, our e x vivo studies with isolated rat hearts indicate hypochloremia aggravates myocardial infarction post ischemia-reperfusion (IR) injury. Hence, to elucidate Cl - mediated signaling mechanism we incorporated highly translational human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Our cellular studies demonstrate that physiological alteration of extracellular Cl - affects the function of beating hiPSC-CM. Hypochloremia significantly increases the beating rate by reducing the calcium cycling durations in hiPSC-CM. Studies are ongoing to determine the involvement of the chloride channel in maintaining chloride homeostasis. Taken together, our results for the first time establish the novel role and mechanism of chloride homeostasis in IR injury. These results will advance the need to search for effective therapeutic approaches to target novel Cl - channels in IHD.

391 Factors affecting electronic dermatology consultations for patients with uncertain cutaneous neoplasms

With the growing incidence of skin cancer globally, electronic consultations (e-consults) can be a useful tool for dermatologists in the assessment of cutaneous lesions. In this study, we sought to characterize the social and institutional factors affecting completion of initial e-consults as well as in-office follow-ups. Patients with an ICD 10 code of neoplasm with uncertain behavior at The Ohio State University Medical Center that received an e-consult order from May 2017 to May 2021 were queried.

Carole A. Miller, MD: Matriarch of the Ohio State University's Department of Neurosurgery

Carole A. Miller, M.D., was born (May 7, 1939) and raised in Kalamazoo, Michigan. She obtained her undergraduate and medical degrees at the Ohio State University. She went on to complete her neurosurgical training at the Ohio State University Medical Center. After her first faculty role at the University of Michigan (1971), she returned to the Ohio State University Medical Center (1975) where she spent nearly 4decades. She thrived in the specialty, achieving in every facet of academic practice including scientific contributions, graduate medical education, clinical care, and leadership roles within her academic department, locally, and at the national level of organized neurosurgery. Dr. Miller passed away peacefully, on October 28, 2015, after a courageous battle with cancer. Based on her essential programmatic and specialty-related contributions, she is remembered as the 'founding mother' of neurosurgery at the Ohio State University.

Prospective two center study of CD38 bright CD8+ effector memory T-cells as a predictor of acute GVHD

IntroductionWe conducted a prospective validation study at Cincinnati Children's Hospital Medical Center and Ohio State University Medical Center to test if absolute CD38 bright CD8+TEM cells > 30/µL would predict acute GVHD, similar to our pilot data. MethodsBlood was collected twice weekly following HSCT. If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. Cells were incubated with alemtuzumab, daratumumab and cyclophosphamide in vitro to determine susceptibility to depletion. ResultsOf the 182 enrolled patients, 83 (45.6%) developed acute GVHD by day+100 but 171 patients were evaluable (acute GVHD n = 77 and no GVHD n = 94). There was no difference in the maximum absolute CD38 bright CD8+TEM cells prior to clinical symptoms and also after CMV and EBV tetramer positive patients were excluded from both cohorts. Ki-67 or Granzyme B expression in patients were comparable between patients with and without acute GVHD. Lastly CD38 bright CD8+ T-cells were effectively depleted with alemtuzumab and cyclophosphamide in vitro. ConclusionAbsolute peripheral blood CD38 bright CD8+TEM cells ≥30 do not predict acute GVHD in a large validation cohort of adult and pediatric HSCT recipients.

822. Tenofovir Alafenamide (TAF) is an Independent Risk Factor for Hyperlipidemia in Persons with Human Immunodeficiency Virus (HIV) on Antiretroviral Therapy (ART)

Abstract Background ART-associated weight gain, metabolic disorders, and co-morbidities such as cardiovascular disease are challenges in long-term human immunodeficiency virus (HIV) care. We explore the effects of different ART classes on lipids at The Ohio State University Medical Center Infectious Diseases Clinic. Methods This was a retrospective, cohort study of adult PWH on ART for ≥ 3 months seen at our clinic from 1/1/2015 to 1/1/2017. Patients with CD4+ count < 200 cells/mm3 and viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. Lipid values were collected over the study period. The primary outcome was change in total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and non-HDL cholesterol over the study period. Multivariable regression was used to model these outcomes. Results Among 411 PWH who met criteria, 87.4% were male, and 43.3% had a baseline diagnosis of hyperlipidemia. 21.1% were on a protease inhibitor (PI), 45% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI), and 37% were on an integrase strand transfer inhibitor (INSTI). 70.1% were on tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC), 20.7% were on abacavir (ABC)/ lamivudine (3TC), and 4.4% were on TAF/FTC. The mean population (MP) difference in TC was -1.54 ± 1.34 mg/dL (p=0.25), the MP difference in non-HDL cholesterol was -1.78 ± 1.26 mg/dL (p=0.16), and the MP difference in HDL cholesterol was 0.24 ± 0.43 mg/dL (p=0.6). In multivariable linear regression models (Table 1), TAF/FTC was associated with a change of TC of 18.2 ± 6.4 mg/dL (P= 0.005), a change of non-HDL cholesterol of 12.0 ± 6.0 mg/dL (p=0.046), and a change of HDL cholesterol of 6.2 ± 2.1 mg/dL (p=0.003). These models included terms for months of follow up, male gender and baseline hyperlipidemia. Though race, diabetes mellitus, and ethnicity were not significant in the model, after adjustments for them, PWH on TAF/FTC showed a change of TC of 18.0 ± 6.4 mg/dL (p=0.005), a change of non-HDL cholesterol of 11.8 ± 6.0 mg/dL (P=0.051), and a change of HDL of 6.2 ± 2.1 (p=0.03). Multivariable Linear Regression Models for Change in Total Cholesterol and Non-HDL Cholesterol Conclusion Prior studies have shown an increase in lipid levels associated with TAF compared to TDF. This study shows that TAF is an independent risk factor for increased TC, non-HDL cholesterol, and HDL cholesterol in the PWH population as a whole. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

Brian Weirich, DHA, MHA, BSN, CENP

Brian Weirich, DHA, MHA, BSN, CENP, is the chief nursing officer (CNO) at Banner Thunderbird Medical Center in Glendale, Arizona. Prior to accepting the CNO position at Thunderbird in 2020, Brian served as the regional CNO for the West Central Region at Indiana University Health and has held leadership roles at University of Colorado Health, Barnes-Jewish Hospital, and Ohio State University Medical Center. Brian is passionate about solving problems facing the industry today by reimagining the current state of health care, specifically, leveraging strengths of the newer generation of nurses, uniting technology and clinicians to ensure improved patient safety and outcomes. He obtained a Certificate in Artificial Intelligence from Northwestern University in Chicago and has cofounded a health care startup company focused on developing innovative technology (Apps/Artificial Intelligence) for nurses. Brian is the recipient of the Advancement in Medicine grant from the IU School of Medicine and is a founding member of the Society of Nurse Scientists, Innovators, Entrepreneurs & Leaders. Brian holds a doctorate in health care administration from The Medical University of South Carolina, a master's in health care administration and bachelor of science in nursing from Ohio University. He is an Ohio native and is married to a nurse he met in nursing school. His wife continues to work in nursing per diem to keep her skills and knowledge up to date. Together, they have 5 very active children (Autumn 11, Tenley 9, River 7, Asher 5, and Brighton 3) who are active in a variety of sports and frequent outdoor adventures.

Reducing Unnecessary Laboratory Utilization in the Medical ICU: A Fellow-Driven Quality Improvement Initiative.

OBJECTIVES:Overutilization of laboratory services is now recognized as harmful to patients and wasteful. In fact, the American Board of Internal Medicine’s Choosing Wisely campaign recommends against ordering routine testing that does not answer a clinical question. Per peer benchmarking, our institution as a whole occupied an extreme outlier position at the 100th percentile for laboratory utilization. We sought to address this problem starting in our medical ICUs with a quality improvement project.DESIGN:Quality improvement project using the design, measure, analyze, improve, and control process. The primary endpoint was a sustained reduction in laboratory utilization. Counterbalance metrics were also followed, and these included mortality, renal replacement therapy initiation rates, stat laboratory orders, and central catheter–associated blood stream infections.SETTING:The medical ICU at the Ohio State University Medical Center.PATIENTS:All patients admitted to the medical ICU from March 2019 to March 2020.INTERVENTIONS:Root causes were identified and addressed with the implementation of a wide range of interventions involving a multidisciplinary team led by trainee physicians.MEASUREMENTS AND MAIN RESULTS:There was a sustained 20% reduction in the number of tests performed per patient day, with no change in the counterbalance metrics.CONCLUSIONS:Trainees can affect positive change in the culture and processes at their institutions to safely reduce laboratory utilization.

Association between anxiety, depression, and emotional distress and hypoglossal nerve stimulator adherence.

To evaluate relationships between hypoglossal nerve stimulator (HNS) adherence and the presence of anxiety, depression, and emotional distress. This is a cross-sectional study of subjects with moderate to severe obstructive sleep apnea (OSA), who had HNS implanted and activated at The Ohio State University Medical Center (OSUMC). Patient usage data from the previous 6 months was obtained from 33 patients. Adherence was defined as ≥28 h of use per week. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were administered, and the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) score was calculated for all subjects. Sixty-five percent were adherent with average usage of 46.5±11.7 h per week vs 7.7±7.5 h per week in the non-adherent group. The average GAD-7 were 3.90±3.98 in the adherent group vs. 8.27±6.69 in the non-adherent group (p=0.049). PHQ-9 score was 6.15±4.31 vs. 10.09±7.53 (p=0.118), and PHQ-ADS was 10.05±7.49 vs. 19.20±9.80 (p=0.035). There were no statistically significant differences in age, gender, pre-treatment AHI, and post-treatment AHI between the two groups, though there was a trend to higher age in the adherent group. This study demonstrated higher GAD-7 and PHQ-ADS scores in the non-adherent group compared to those who were adherent to HNS supporting thatanxiety and emotional distress may contribute to HNS therapy adherence. To our knowledge, this is the first study evaluating the relationship between anxiety, depression, emotional distress, and HNS adherence. Screening patients with the GAD-7 and PHQ-9 prior to implantation may be helpful when evaluating patient adherence to therapy.

Erratum: Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells.

An erratum was issued for:Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells. The author list was updated. The author list was updated from: Katie A. Thies1,Sue E. Knoblaugh2, and Steven T. Sizemore1 1Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center 2Department of Veterinary Biosciences, Comparative Pathology and Digital Imaging Shared Resource, The Ohio State University to: Katie A. Thies1, Sarah Steck1, Sue E. Knoblaugh2, and Steven T. Sizemore1 1Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center 2Department of Veterinary Biosciences, Comparative Pathology and Digital Imaging Shared Resource, The Ohio State University.

Convergence of Digital Pathology and Artificial Intelligence Tools in Anatomic Pathology Practice: Current Landscape and Future Directions

*Department of Pathology, The Ohio State University Medical Center, Columbus, OH †Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN A.V.P. serves on the advisory board for Contextvision and provides advice on deep learning and artificial intelligence applications in Anatomic Pathology. M.B.A. serves on the advisory board for Ibex and is a consultant for Advanced Clinical providing consultations for artificial intelligence applications in Anatomic Pathology for both these organizations. Reprints: Anil V. Parwani, MD, PhD, MBA, Department of Pathology, The Ohio State University Wexner Medical Center, 410 W.10th AVE, Columbus, OH 43210 (e-mail: [email protected]).

Hypochloremia at Left Ventricular Assist Device Implantation is Associated with Decreased One Year Survival

Serum chloride has been independently and inversely associated with mortality in acute decompensated heart failure. The impact of serum chloride on other subsets of the heart failure population is unclear. We sought to investigate the effects of hypochloremia in patients undergoing left ventricular assist device (LVAD) implantation. We reviewed 289 patients who received a HeartMate II or HeartWare LVAD between 6/2006 and 12/2016 and were admitted to The Ohio State University Medical Center for care. Patients were stratified based on serum chloride level at time of LVAD placement and compared based on demographics and major comorbidities. We defined hypochloremia as serum chloride <96 mEq/L, and normochloremia, as a serum chloride ≥96 mEq/L. A survival analysis was performed to determine the impact of serum chloride on mortality following LVAD implantation. There were no significant differences in baseline demographics between the low and normal serum chloride cohorts. The hypochloremic subset had an average serum chloride of 91.5 (87.7-95.5) mEq/L. Meanwhile, the normochloremic subset had an average serum chloride of 101.7 (97.3-106.2) mEq/L. We found that patients with hypochloremia were more likely to have a history of myocardial infarction (MI), odds ratio (OR) 1.87 [1.06-3.31], p=0.030. This relationship was maintained when adjusted for age and gender, hazard ratio (HR) 1.93 [1.07-3.47], p=0.027. Lastly, survival analysis demonstrated that patients with hypochloremia at LVAD placement had decreased survival at one year compared to patients with normal serum chloride (p=0.0055) (Figure 1). Hypochloremia at LVAD placement is associated decreased mortality at one year. Thus, serum chloride has the potential to affect management of patients being evaluated for LVAD implantation. Nonetheless, further investigation is needed into the interplay of chloride and sodium to derive additional prognostic information in this population.

The Construction of Case-Specific Resident Learning Goals

Developing resident autonomy in the operating room is a complex process and resident established case specific learning goals may increase resident operating room training efficiency. However, little is understood about residents' experience identifying learning goals for a given case. The aim of this study was to explore the essential components contributing to surgery residents' identification of specific learning goals for surgical cases. We conducted focus group interviews with general surgery residents across all post-graduate years (PGY) through convenience sampling. Audio recordings of each interview were transcribed and iteratively analyzed. Emerging themes were identified using a framework method. The study was conducted within the Department of General Surgery at the Ohio State University Medical Center, a tertiary academic medical center. Eight junior (PGY 1-2) and 10 senior (PGY 3-5) residents participated, of whom 10 were female and 8 were male. On average, each focus group interview lasted 57.00 (SD ± 12.99) minutes. Three essential components of residents' creation of case-specific learning goals emerged from the focus group interviews: medical knowledge, surgical experience and entrustment. Residents require baseline knowledge and surgical experience with an operation to identify the learning goal they would aim to execute. They also require entrustment of themselves and support of the attending to accomplish the case specific learning goal. Differences in the possession of these three components would likely influence differences in the ability to create learning goals between junior and senior residents. Medical knowledge, surgical experience and entrustment are 3 factors that are imperative to the creation of a resident's case specific learning goal. The complex combination of these three components contributes to the building of the learning goal prior to the start of the operation. Elucidating these aspects provides additional information for targeted interventions in the future.

Concurrent Treatment of VEGFR Tyrosine Kinase Inhibitors (TKIs) and Factor Xa Inhibitors Is Associated with Increased Bleeding Risks

ABSTRACT Background: Some cancer patients with thromboembolism require dual treatment of VEGFR TKIs and factor Xa inhibitors (direct or indirect), which may contribute to increased bleeding risks. However, the safety of such combination treatment has not been well characterized in the literature or national guidelines. Methods: This is a single center retrospective study, where we identified metastatic cancer patients (renal cancer, colorectal cancer, sarcoma, etc) who received concurrent VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib or cabozantinib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs] including rivaroxaban or apixaban) at the Ohio State University Medical Center. We assessed bleeding risks of dual therapies vs. factor Xa inhibitors alone, using the same patients as self controls. We reviewed medical charts of all identified patients for clinically significant bleeding events (defined as combined major bleeding and clinically relevant non-major bleeding by the International Society of Thrombosis and Haemostasis criteria). The Cox proportional hazard model was used to compare the differences of time to first clinically significant bleeding event between the groups of concurrent use and anticoagulant use only. Results: A total of 86 patients (26 females and 60 males) were included: 78 Caucasians, 6 African Americans, and 2 others. 81 patients had concurrent TKI and LMWH treatment; 20 patients had concurrent TKI and DOACs; and 85 patients have had been on factor Xa inhibitor alone (LMWH or DOACs) at some point. Some patients had been on both LMWH and DOACs at different time periods. Overall, there were 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment and 17 events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days (52 days for concurrent treatment and 99 days for Xa inhibitor alone). In this self-control study, concurrent treatment was associated with a statistically higher risk of clinically significant bleeding events (HR, 2.84; 95% CI, 1.43-5.64, P &amp;lt; 0.01), which reached 37% patient population in the first 3 months, while the bleeding associated with factor Xa inhibitor alone seemed spaced out at the entire length of anticoagulation (8% by 6 months). Similar trend was found in the analysis of patient group of concurrent TKI and LMWH vs. LMWH alone (HR, 1.96; 95% CI, 0.95-4.02, P = 0.067), although significance was not reached likely due to insufficient power. Sample size was inadequate for meaningful comparison between concurrent VEGFR TKI and DOAC vs. DOAC alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with a significantly increased bleeding risks when compared with factor Xa inhibitors alone in patients with metastatic cancer. Disclosures No relevant conflicts of interest to declare.

Jerry A. Mansfield Interview

Leadership is a journey, particularly for individuals who influence patient care delivery in hospitals and health care systems throughout the globe. For the nurse leader, it is a daily focus on a myriad of fronts including staff engagement, patient experience, quality and safety and financial performance. Dr. Mansfield made the decision to become a Registered Nurse because of the difference one RN made during his hospitalization as a teenager. This leadership profile offers one leaders’ perception of current challenges and opportunities in the industry; a time of unprecedented and transformative change in health care.

Circulating Gasdermin-D in Critically Ill Patients.

Objectives:The key to further improving outcomes in sepsis lies in understanding and abrogating the dysfunctional immune response that leads to organ failure. Activation of gasdermin-D, a pore-forming protein within the inflammasome cascade, has recently been recognized as the critical step in pyroptosis and organ dysfunction. In this study, we sought to investigate the presence of gasdermin-D in critically ill subjects.Design, Setting, and Patients:Prospective pilot study comparing microparticulate active gasdermin-D levels in critically ill patients admitted to the medical ICU at The Ohio State University Medical Center to healthy donors and clinical outcomes.Interventions:None.Measurements and Main Results:Plasma was collected from subjects upon consent and microparticles were isolated by ultracentrifugation. Proteins of interest were identified by immunoblot analysis of microparticle lysates. Quantification was accomplished by densitometry using ImageJ software (National Institutes of Health, Bethesda, MD). Investigators were then unblinded and compared microparticulate active gasdermin-D levels to physician adjudicated clinical diagnoses and outcomes. No appreciable levels of active gasdermin-D were observed in microparticles from healthy volunteers and nonseptic critically ill patients. However, elevated levels of gasdermin-D were noted in microparticles from the septic cohort of critically ill patients. Furthermore, a significant positive correlation by linear regression was noted when microparticulate active gasdermin-D levels were compared with microparticulate levels of CD63, an exosomal marker, CD14, a monocyte marker, and CD69, a marker of monocyte activation (R2 = 0.37, p = 0.0011, R2 = 0.85, p < 0.0001, and R2 = 0.43, p = 0.0003, respectively).Conclusions:This is the first study to demonstrate circulating active gasdermin-D in septic patients in the intensive care setting. Our findings also suggest that active gasdermin-D in septic patients is encapsulated in exosomes derived from activated monocytes. Further characterization in the clinical setting is warranted.

QIM19-143: Reducing Risk of IV Chemotherapy Administration Errors Utilizing Pump Integration Technology

Background: The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solve Research Institute is a 356-bed cancer care hospital that is part of The Ohio State University Medical Center. In addition to the inpatient beds, the hospital services 175 ambulatory infusion chairs. Each month, we administer over 6,000 chemotherapy infusions on an IV pump. Smart IV pumps in tandem with hospital information technology infrastructure integrate IV drug administration pump data with the electronic medical record (EMR) and computerized physician order entry to decrease risk of error and increase patient safety. The closed loop system transmits the medication infusion rate and the prescribed dose to the smart pump to deliver the medication. The smart pump in turn transmits the dose and volume delivered to the EMR to accurately capture what the patient received. The ability to wirelessly transmit clinical information from the EMR to automatically program the IV pump with specific data was implemented in March 2018 as part of a system-wide safety initiative to enhance patient safety via the reduction of error during medication administration. Methods: IV pump integration has been in use since March 2018; the organization has robust data on the use of smart pump technology that allowed for comparison of data pre- and postimplementation of pump integration. This includes: total suite usage, count of basic infusions, severe harm averted, total good catches, and event-reporting data. Post-integration, the overall compliance of utilizing pump integration (sending an order from the EMR to the smart IV pump) is also continuously monitored. Results: The implementation of pump interoperability resulted in a safer delivery of infused medications (Figure 1). The use of “basic Infusion” or unprotected infusion function decreased while our use of the appropriate safeguarded pump program increased. The compliance at the medical center increased from about 86% to almost 94%. With increased usage of the pump interoperability, the potential for severe harm as well as human programming errors decreased significantly. Conclusion: The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solve Research Institute is able to deliver infused medications via a smart pump in a safer, more automated system with the implementation of pump integration. We are able to reduce the “human factor” in medication delivery by reducing keystrokes and opportunities for manual programming errors. Pre-integration data cannot be isolated for the cancer hospital only, from our post-implementation data we can infer that our chemotherapy infusions are subsequently safer for our patients.

189: PL-12 POSITIVE ANTISYNTHETASE SYNDROME COMPLICATED BY FULMINANT CARDIOGENIC SHOCK

1The Ohio State University Medical Center, Columbus, OH 2The Ohio State University Medical Center, Columbus, OH

690: AN UNUSUAL CASE OF AN UNDIFFERENTIATED BULLOUS RASH LEADING TO MACROPHAGE-ACTIVATING SYNDROME

1The Ohio State University Medical Center, Columbus, OH 2Nationwide Children’s Hospital, Columbus, OH