bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1858. Exploring the Role of Fatty acid synthase (FASN) Inhibition in Interferon Gamma Mediated Killing of Histoplasma capsulatum
Authors: Nair Resmi , Buesing William , Rossi Diego , Deepe George S 
Published: January 2025

Abstract

Background
Histoplasma capsulatum (Hc) is the leading cause of fungal respiratory infections in the US. Most cases are mild but 20% require hospitalization. Immunosuppression is a major risk factor for disseminated histoplasmosis. The cytokine Interferon gamma (IFN)-γ is crucial for host resistance to Hc. The absence of IFN-γ or its failure to signal affects the host immune response.
Activated CD4+ T cells release IFN-γ to arm macrophages(MΦ) to kill intracellular yeasts. Immunometabolism is a key element in the function of MΦ and fatty acid synthase (FASN) regulates inflammatory responses by these cells. FASN is a large multi-enzyme complex comprised of 6 separate enzymatic grooves that work together to produce 16-carbon chain saturated fatty acid (FA), palmitate, from acetyl-coenzyme A (CoA) and malonyl-CoA(Figure 1). The influence of FASN in the IFN-γ-mediated activation of MΦ remains unclear.

Key inhibitor targets in FASN complex

Methods
Figure 1 shows key inhibitor targets in FASN complex. Bone marrow derived Mφ were used in all experiments with a 2 to 1 yeast to Mφ ratio. IFN-γ induced killing of Hc in mouse Mφ require 48h. We used the tetrazolium salt XTT to assess the Hc viability as this correlates with the colony counts. Controls (Hc in Mφ) are set to 100 %. Toxicity of each inhibitor to Hc and Mφ was studied first.
Mφ were treated with IFN-γ 4hrs before infection and then treated with graded amounts of FASN inhibitors C 75 (inhibits ketoacyl synthase), orlistat (inhibits thioesterase), and TVB-3166 or GSK2194069 (both inhibit ketoacyl synthase) 2hrs before infection with 2x Hc for 48hrs. Intracellular yeast survival at 48hrs was assessed.

Effect of FASN inhibitors on IFN- γ mediated killing of Hc at 48 hrs.
n= 3-10 , mean ±SEM

Results
Pretreatment with the FASN inhibitor C75 reversed the killing activity of IFN- γ. Neither orlistat or inhibitors of ketoacyl reductase modified the impact of IFN-γ. (Figure 2)

Conclusion
The FASN inhibitor C75 reversed the activity of IFN-γ in killing Hc. These results suggest that cholesterol synthesis may be involved in the action of IFN- γ.

Disclosures
All Authors: No reported disclosures
P-1878. Intravenous Ganciclovir Administration Outcomes via an Outpatient Parenteral Antimicrobial Therapy (OPAT) Program
Authors: Patel Dhruv , Mynatt Ryan P , Logan Ashley , Cari Evelyn Villacorta , Mansoor Armaghan-E Rehman 
Published: January 2025

Abstract

Background
Intravenous (IV) ganciclovir is used in the management of herpesvirus infections including cytomegalovirus (CMV). Ganciclovir is usually administered in the inpatient setting given the need for close monitoring of hematologic and renal parameters. This study describes our experience with IV ganciclovir administration in immunocompromised hosts, via an OPAT program at a tertiary academic medical center. Ganciclovir was chosen as choice of therapy either due to concern for GI absorption, or provider preference.

Methods
This is a retrospective, single-center review of patients discharged on IV ganciclovir via OPAT from August 2019 to December 2023. Patient demographics, underlying diagnoses, indication for ganciclovir, duration of therapy, treatment outcomes and adverse events were collected.

Results
We included 18 patients whose mean age was 58.6 (SD±12.4) years, with ten (55.6%) being male. The most common underlying immunocompromising condition was receipt of a transplanted organ in 15 (83.3%) patients, including five and ten recipients of hearts and kidneys, respectively. The mean duration of therapy was 25 (SD±11) days. In our cohort, 13 were treated for CMV disease as follows; 11 patients with gastrointestinal involvement and two patients with encephalitis/retinitis. Four patients had isolated viremia and one patient was treated for Epstein Barr Virus encephalitis. A majority (13 patients, 72.2%) transitioned to valganciclovir on completion of parenteral therapy for secondary prophylaxis or to continue induction therapy.
The most common adverse event was worsening cytopenia in four (22.2%) patients, one of whom had baseline leukopenia. Neutropenia was documented in three patients, and one patient had thrombocytopenia. One (5.6%) patient developed acute kidney injury (AKI) through their treatment, requiring dose modification.

Conclusion
Ganciclovir is a viable option for outpatient parenteral therapy in the treatment of CMV disease where an extended duration of IV therapy is required. In our cohort of 18 immunocompromised patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs through an established OPAT protocol is needed for successful completion of therapy.

Disclosures
All Authors: No reported disclosures
P-1884. Evaluation of Outpatient Parenteral Antimicrobial Therapy Practices within a Large Healthcare System
Authors: Beran Christina , Kim Chungyun , Wings Emily , Pallotta Andrea , Shrestha Nabin K 
Published: January 2025

Abstract

Background
The practice of outpatient parenteral antimicrobial therapy (OPAT) has challenges such as reduced control and monitoring in the outpatient setting. Lack of availability of OPAT lab monitoring is associated with poorer outcomes. This study sought to describe the operations and practices of an OPAT program within a large health system to identify clinical and operational opportunities for workflow improvement.
Laboratory monitoring completion over proportion of OPAT courses

Methods
This was a retrospective cohort study of patients receiving OPAT in a large healthcare system from January 1, 2022 to December 31, 2022. After excluding OPAT courses initiated in the outpatient setting and courses less than 7 days long, 200 OPAT courses for patients greater than 18 years of age were selected, using a random sample generator, from the Cleveland Clinic OPAT registry. Events were followed until the OPAT end date or 30 days, whichever occurred sooner. The relationship between lab monitoring completion within 24 hours of scheduled date and detection of clinically significant lab abnormalities (CSLAs) was examined using linear regression. Secondary outcomes included the rate of emergency department (ED) visits and readmissions.
Cumulative incidence of ED visits by target lab monitoring level

Results
The mean age (SD) of included patients was 63 years (27) and 64% were male. Fewer than half the OPAT courses had 80% or higher lab monitoring completion (Figure 1). Detected CSLAs are shown in Table 1. In a linear regression model adjusted for high-risk medications, the number of CSLAs detected per OPAT course increased by 0.003 (95% C.I. 0.002 – 0.004) per unit increase in percentage lab monitoring completion (p &lt; 0.001). ED visit within 30 days was 11% (Figure 2) and readmission within 30 days was 23% (Figure 3). Reasons for readmission included non-OPAT-related (53%, n=24 of 45), infection-related (40%, n=18 of 45), and adverse OPAT drug effects (9%, n=4 of 45).
Cumulative incidence of readmissions by target lab monitoring level

Conclusion
This study showed a substantial gap in lab completion and a significant association between lab monitoring completion and detection of CSLAs, thereby demonstrating clinical and operational opportunity for OPAT workflow improvement with monitoring and follow-up actions. A multidisciplinary OPAT team with clearly defined roles may enhance safety, effectiveness, and efficiency within the program.
Detection of Clinically Significant Lab Abnormalities

Disclosures
Andrea Pallotta, PharmD, Astra Zeneca: Advisor/Consultant|Viiv: Advisor/Consultant
P-1885. Continuous Infectious Diseases Coverage by Merging with a Hospitalist Practice in a Small Community Hospital System
Authors: Wang Michael , Aleksoniene Kristina , Tompkins Jason , Douce Richard , Froggatt John , Harrison Mark 
Published: January 2025

Abstract

Background
There is a severe shortage of infectious diseases (ID) physicians in the United States, with &gt; 80% counties without an ID physician. Insufficient compensation is a contributing factor, with many internal medicine graduates practicing as hospitalists. Based on community needs, we merged the ID practice into the hospitalists group to create an ID-Hospitalist position.

Methods
Corewell Health South is based in Berrien County, which is in Southwest Michigan, population 152,261, and includes large rural populations and several federally funded clinics. The hospital includes 2 acute care facilities, including 220-bed and 76 bed hospitals. In 2002, the ID physicians began seeing patients as hospitalists at a Long-Term Acute Care Hospital. An ID physician assumed the role of Hospitalist Director in 2005 and second physician became co-director in 2008. At that time, the ID service adopted a 7 day on-7 day off schedule and included primary hospitalist patients.

Results
Since 2011, the ID-Hospitalist group has had continuous coverage with at least 3 Full time and 1 part-time ID-Hospitalists. Coverage (2.63/100,000) exceeds the national average of 1.79/100,000 by 84%. All service weeks are based on a 7 day on-7 day off schedule. In 2013, the outpatient ID clinic was resumed after a 5-year hiatus and is Ryan White Funded. A clinic day is built into the 7-day work week. Over the last 22 years, the group has included 6 ID physicians, which include 5 American graduates and 1 international graduate. In surveying the group, 83% expressed that pay was a factor in working as an ID/Hospitalist. 67% reported more free time and improved work-life balance. 67% preferred doing ID only, although the majority enjoyed hospitalist practice.
Perceived weaknesses included overextension of responsibilities and a de-emphasis on the ID service in favor of hospitalist responsibilities. Another limitation included inconsistent coverage at the smaller hospital, increasing the reliance on telephone consultations.

Conclusion
Merging an ID practice into a hospitalist group has been effective in sustaining an ID service. Strengths included stable salary support and ability to perform other administrative or clinical tasks. Weakness included a multitasking of duties. This may serve as a model for resource limited settings.

Disclosures
All Authors: No reported disclosures
P-1894. Evaluation of an Outpatient Parenteral Antimicrobial Therapy (OPAT) Program Performance Against Published Key Performance Indicators (KPIs)
Authors: Slain Nicole , Mynatt Ryan P , Logan Ashley , Burgess Donna R , Clemons Alisha , Mansoor Armaghan-E Rehman , Ruf Kathryn , Cari Evelyn Villacorta 
Published: January 2025

Abstract

Background
Current OPAT guidelines emphasize identifying, reporting and improving key antimicrobial use and care coordination decisions. There is no clear guidance on benchmarking or consensus reporting recommendations. We examined our OPAT program’s performance against data published from Great Britain’s National Outcomes Registry System (NORS) as well as a meta-analysis on catheter related thrombosis (CRT) in OPAT (Figure 1).

Methods
Adult patients receiving OPAT from infectious diseases (ID) ambulatory and inpatient consult teams from June 2021 to July 2022 were included. Patient demographics, admission data, and OPAT outcomes were recorded as part of routine pharmacist workflow. Data were compared against those reported via the NORS registry as well as a meta-analysis evaluating CRT. Specific comparisons relative to reported rates and ranges were made in key clinical areas including infection type, clinical outcomes, OPAT completion, VAD events, adverse drug events (ADEs) and medication-related events. Given limitations to available published data, a statistical comparison was not performed.

Results
Overall, 913 OPAT episodes were identified. Infections observed at our institution were more invasive and required longer treatment durations (Table 1). Outcomes were known in 798 (87.4%) patients, with improvement/cure reported in 689 (86.3%) in comparison to 92.4% (number not reported) in the NORS registry (Table 2). Institutional performance relative to VAD-related events was within the ranges observed by both NORS (1.4 per 1000 OPAT days vs. 1.4 per 1000 OPAT days [reported range: 0.11 – 10.4]) and meta-analysis (Table 3). These rates remained comparable when further classified as either infection-related or CRT. In our OPAT cohort, rates of catheter removal events and medication errors were rare, occurring in 0.5 and 0.6 events per 1000 OPAT days, respectively. These were novel OPAT metrics not reported in the comparator registry.

Conclusion
Compared to the NORS national registry, infections managed with OPAT at our institution were more deep-seated and required longer durations of therapy. However, our reported clinical outcomes at the end of therapy remained comparable and were within reported ranges.

Disclosures
Alisha Clemons, APRN, Gilead Sciences: Honoraria
P-1904. The Interaction of Serum Biomarkers and Lymphopenia on Pulmonary COVID-19 Illness Progression in Hospitalized Patients
Authors: Benitez Gregorio , Kaczynski Matthew , Vassilopoulos Stephanos , Vassilopoulos Athanasios , Shehadeh Fadi , Tashima Karen T , Mylonakis Eleftherios 
Published: January 2025

Abstract

Background
Low absolute lymphocyte count (ALC) as well as elevated levels of plasma nucleocapsid antigen (N-antigen) and C-reactive protein (CRP) are independently associated with COVID-19 clinical outcomes. We evaluated the potential additive interaction of these three prognostic markers on the progression of pulmonary COVID-19 illness.

Methods
We utilized publicly available data to perform a secondary analysis of hospitalized adults who enrolled into the Therapeutics for Inpatients with COVID-19 platform trial (NCT04501978). Plasma N-antigen level &gt; 1000 ng/L, CRP level &gt; 75 mg/L, and ALC &lt; 1.5x109/L, all measured at baseline, were the three prognostic markers of interest. The outcome of interest was worsened pulmonary status, dichotomized as either worse or same/better than baseline status on a 7-point ordinal scale, at day 5. Estimated coefficients from modified multivariable Poisson regression were utilized to calculate risk ratios. We then calculated relative excess risk due to interaction (RERI) to evaluate departure from additivity. We present a measure of excess risk due to the respective two-way interactions when one of the markers is absent (RERI2), a measure of excess risk due to the three-way interaction (RERI3), and a total summation of excess risk (TotRERI).

Results
A total of 2,478 enrolled patients were included in our complete-case analysis (Figure 1). The interaction of low ALC, elevated plasma N-antigen level and elevated CRP level on worsened pulmonary status at day 5 may be super-additive (TotRERI = 0.88, 95% confidence interval (CI): -0.71 – 2.48) (Table 1). This 88% excess risk of worsened pulmonary status is mainly due to the explicit three-way interaction (RERI3: 1.56, 95% CI: -0.77 – 3.89). Sensitivity analysis utilizing multiple imputation to address missing data revealed similar estimates: TotRERI: 0.87 (95% CI: -0.79 – 2.53) and RERI3: 1.70 (-0.74 – 4.14).

Conclusion
Our data suggest that the interaction of low ALC, elevated plasma N-antigen level and elevated CRP level may be associated with excess risk of worsened pulmonary COVID-19 illness among hospitalized patients. Further evaluation regarding the interaction of prognostic markers in identifying patients at high-risk of pulmonary deterioration is supported.

Disclosures
Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH SciClone Pharmaceuticals: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support
P-1927. Utilization of Patient Characteristics and the Area Deprivation Index (ADI) To Evaluate Referral Patterns for Long COVID at a Tertiary-Care Veterans Affairs (VA) Medical Center
Authors: Brennan Martha , Wilson Brigid , Stiefel Usha 
Published: January 2025

Abstract

Background
The COVID-19 pandemic disproportionally affected socioeconomically disadvantaged communities, with corollary expectation of increased impact of post-acute sequelae in this population. We established a subspecialty Long COVID Clinic (LCC) at VA Northeast Ohio to care for patients with post-acute sequelae of COVID-19 in 2023. The LCC was advertised system-wide to providers via email and videoconference presentations, and to patients via the facility website. After the first 1/2 year of implementation, an analysis of patients and of referral adequacy in meeting the needs of the catchment area was undertaken.

Methods
The Area Deprivation Index (ADI) uses census data to rank US neighborhoods by socioeconomic disadvantage and can be a tool in refining delivery of services or healthcare. Neighborhoods are ranked nationally and within-state (state deciles 1-10, with 10 indicating greatest disadvantage). In addition to other health factors, national and state ADI indices were obtained for each patient seen in our LCC between March 2023 and April 2024.

Results
70 unique patients (mean age 63) were seen via referral in the 1st 8 months of the LCC (Fig 1). These were 13 (19%) women, 55 (79%) men, 2 (1%) transgender, 10 (14%) Black and 54 (77%) White. The most common comorbidities were psychiatric (57%), hypertension (44%) and cardiac (40%) (Fig 1). The most common presenting complaints were fatigue (73%), exercise intolerance (72%), and dyspnea (52%) (Fig 2). ∼1/4 of LCC patients had experienced severe COVID-19 (Fig 3). The average in-state ADI decile was 5 (range, 1-10).

Conclusion

Disclosures
All Authors: No reported disclosures
P-1943. Risk Factors for Coronavirus disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis (CAPA) in Critically Ill Patients: The Predictive Value of KL-6 for CAPA and Mortality
Authors: Lee Seung Min , Kim Si-Ho , Jeon Cheon-Hoo , Wi Yu Mi 
Published: January 2025

Abstract

Background
Coronavirus Disease 2019 (COVID-19) is an acute respiratory viral illness that can be complicated by secondary invasive fungal infections, such as COVID-19-Associated Pulmonary Aspergillosis (CAPA). Krebs von den Lungen-6 (KL-6), a mucinous high-molecular-weight glycoprotein found on the surface of type II alveolar epithelial cells, has been known as a biomarker indicative of respiratory epithelial damage. This study aims to evaluate the risk factors for CAPA in critically ill COVID-19 patients, with a focus on the predictive value of KL-6.
Overall 30-day survival rates between patients with and without CAPA

Methods
This single-center retrospective cohort study included critically ill COVID-19 patients (those requiring high-flow respiratory support or mechanical ventilation) admitted from January 2021 through June 2023. CAPA diagnosis was established based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. The study investigated factors associated with CAPA and compared overall 30-day mortality for patients with and without CAPA.

Results
Among 238 critically ill COVID-19 patients, 25 (10.5%) were diagnosed with CAPA. Notably, patients with CAPA exhibited significantly higher median serum peak levels of KL-6 (787.4 vs. 290.2 U/mL, P&lt; 0.001), with a cutoff value of 392.9 U/mL determined by the Youden index. Multivariable analysis revealed that a peak KL-6 level ≥ 392.9 U/mL was strongly associated with CAPA (adjusted odds ratio 8.62, 95% confidence interval [CI] 2.43-31.69). Additionally, inotropics/vasopressor support, diabetes mellitus, and tocilizumab were identified as factors associated with the development of CAPA. The overall 30-day mortality was significantly higher in patients with CAPA (60.8%) compared to those without (45.2%) (P=0.020), with the difference persisting after adjustment (adjusted hazard ratio 2.06, 95% CI 1.05-4.03). Furthermore, along with older age, lacticemia, and diabetes mellitus, elevated KL-6 was also associated with increased mortality.

Conclusion
Our study suggests that KL-6 may be a significant predictor of both the development of CAPA and mortality among critically ill patients with COVID-19.

Disclosures
All Authors: No reported disclosures
P-1952. SARS-CoV-2 Self-Testing Modalities Demonstrate Concerning Inaccuracies Among Rural, Minority Populations: The ALL-IN SC Study
Authors: Meyer Madeleine M , Self Stella C W , Daguise Virginie , Nolan Melissa 
Published: January 2025

Abstract

Background
At-home, diagnostic self-test assays provide a unique opportunity to reduce healthcare disparities by providing low-cost, immediate access to disease testing. Despite their utility, their real-world accuracy is unknown. Therefore, this study aimed to evaluate multiple testing modalities among diverse, marginalized populations in a large, multi-year, state-wide randomized controlled trial.

Methods
From 2022 to 2023, 2,195 individuals participated in testing events across South Carolina, USA. Participants provided medical personnel collected samples for gold standard laboratory comparison and were assigned to one of three groups for a matching self-test comparison. These groups were 1) no assistance self-test (only provided manufacturer self-test instructions), 2) unassisted hybrid (collected their own samples according to manufacturer instructions and mailed-in samples to laboratory), and 3) assisted (medical personnel verbally explained the manufacturer’s instructions). A robust statistical analysis plan was executed; however, only the results from multivariate regression are described here.

Results
Participants in the unassisted groups were significantly more likely to have an incorrect self-test result. Conversely, participants with assistance were 32% more likely to have a correct self-test result, regardless of testing modality (saliva, dried blood spot, nasal swab). Self-collection of saliva samples to send to a laboratory for testing had the highest odds of inaccuracy (OR=9.21, p-value &lt; 0.001). Self-collection of dried blood spot samples sent for laboratory testing had the lowest odds of inaccuracy (OR=1.52, p-value&lt; 0.021). Demographic risk factors varied by testing modality, with females, black, and lower income participants statistically more likely to have inaccurate testing results. Select infection symptoms at the time of testing also increased the odds of inaccuracy.

Conclusion
This study provides critical evidence that self-tests are a viable option for addressing health care access disparities, but telemedicine and/or community assistance programs must also be provided to ensure tests are conducted and interpreted correctly.

Disclosures
All Authors: No reported disclosures