scholarly journals Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1696
Author(s):  
Martin Benej ◽  
Jinghai Wu ◽  
McKenzie Kreamer ◽  
Martin Kery ◽  
Sergio Corrales-Guerrero ◽  
...  
Keyword(s):  
Medical Center ◽  
Tumor Hypoxia ◽  
Tumor Oxygenation ◽  
Mitochondrial Metabolism ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Murine Tumors ◽  
Small Series ◽  
Canine Tumors ◽  
The Impact

Background: Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors. Methods: We used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine. Results: We showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10–50 mm HgO2. Conclusion: In both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage.

scholarly journals To fractionate or not to fractionate? That is the question for the radiosurgery of hypoxic tumors

2014 ◽  
Vol 121 (Suppl_2) ◽  
pp. 110-115 ◽  
Author(s):  
Iuliana Toma-Dasu ◽  
Helena Sandström ◽  
Pierre Barsoum ◽  
Alexandru Dasu
Keyword(s):  
Tumor Hypoxia ◽  
Tumor Oxygenation ◽  
Medium Size ◽  
Tumor Control ◽  
Tumor Control Probability ◽  
Single Fraction ◽  
Potential Gain ◽  
Treatment Plans ◽  
Effective Doses ◽  
The Impact

ObjectThis study aimed to investigate the impact of tumor hypoxia on treatment outcome for metastases commonly treated with radiosurgery using 1 fraction of radiation and the potential gain from reoxygenation if the treatment is delivered in a few radiation fractions.MethodsIn silico metastasis-like radiosurgery targets were modeled with respect to size, density of clonogenic cells, and oxygenation. Treatment plans were produced for the targets using Leksell GammaPlan, delivering clinically relevant doses and evaluating the tumor control probability (TCP) that could be expected in each case. Fractionated schedules with 3, 4, and 5 fractions resulting in similar biological effective doses were also considered for the larger target, and TCP was determined under the assumption that local reoxygenation takes place between fractions.ResultsThe results showed that well-oxygenated small- and medium-size metastases are well controlled by radiosurgery treatments delivering 20 or 22 Gy at the periphery, with TCPs ranging from 90% to 100%. If they are moderately hypoxic, the TCP could decrease to 60%. For large metastases, the TCPs from single-fraction treatments ranged from 0% to 19%, depending on tumor oxygenation. However, for fractionated treatments, the TCP for hypoxic tumors could significantly increase up to 51%, if reoxygenation occurs between fractions.ConclusionsThis study shows that hypoxia worsens the response to single-fraction radiosurgery, especially for large tumors. However, fractionated therapy for large hypoxic tumors might considerably improve the TCP and might constitute a simple way to improve the outcome of radiosurgery for patients with hypoxic tumors.

scholarly journals Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Yang ◽  
Li’e Zang ◽  
Jingwen Cui ◽  
Linlin Wei
Keyword(s):  
Stem Cells ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neural Stem Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cerebral Ischemia Reperfusion ◽  
The Impact

Abstract Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

scholarly journals The Fellow’s Perspective: The Impact of the COVID-19 Pandemic on Fellowship Training and Job Appointment

2021 ◽  
pp. 000313482110241
Author(s):  
Adam Truong ◽  
Farin Amersi ◽  
Van Chau ◽  
Taryne Imai
Keyword(s):  
Clinical Training ◽  
Medical Center ◽  
Fellowship Training ◽  
Surgical Specialty ◽  
Job Interview ◽  
Educational Structure ◽  
Global Pandemic ◽  
Procedural Volume ◽  
Interview Format ◽  
The Impact

Background Fellows have been uniquely affected by the widespread changes in educational structure, mandatory limitations in elective procedural volume, and hiring freezes during the COVID-19 global pandemic. Study Design A voluntary and anonymous survey was distributed to all Graduate Medical Education fellows at a tertiary medical center querying perspectives on clinical and didactic training and job placement. Results A total of 47 of 121 fellows (39%) completed the survey. The majority were in a medical (43%) or surgical specialty (34%) followed by critical care (13%) and procedure-based (11%) fellowships. Approximately 59% of surveyed fellows felt their programs were providing a virtual curriculum that would train them just as well as the in-person curriculum. Twenty-eight (60%) fellows were in their final or only year of training. Of the 25 fellows who were seeking employment, 52% have experienced difficulty in finding a job due to hiring freezes and 40% have encountered challenges with job interview cancellations and changes to virtual interview formats. Conclusion Almost half of surveyed fellows reported an educational deterioration due to COVID-19 and graduating fellows seeking employment felt hindered by both the virtual interview format and widespread hiring freeze. Fellows are both unique and vulnerable as they balance the solidification of clinical training with securing employment during these tumultuous and unprecedented times.

scholarly journals Alcohol Hand Rub Significantly Reduces Overall Bacterial Bioburden on Stethoscopes in a Real-World Clinical Setting

2020 ◽  
Vol 41 (S1) ◽  
pp. s114-s115
Author(s):  
Alexandra Johnson ◽  
Bobby Warren ◽  
Deverick John Anderson ◽  
Melissa Johnson ◽  
Isabella Gamez ◽  
...  
Keyword(s):  
Real World ◽  
Medical Center ◽  
Academic Medical Center ◽  
Randomized Study ◽  
Healthcare Providers ◽  
Clinical Workflow ◽  
Provider Type ◽  
Academic Medical ◽  
Rn Students ◽  
The Impact

Background: Stethoscopes are a known vector for microbial transmission; however, common strategies used to clean stethoscopes pose certain barriers that prevent routine cleaning after every use. We aimed to determine whether using readily available alcohol-based hand rub (ABHR) would effectively reduce bacterial bioburden on stethoscopes in a real-world setting. Methods: We performed a randomized study on inpatient wards of an academic medical center to assess the impact of using ABHR (AlcareExtra; ethyl alcohol, 80%) on the bacterial bioburden of stethoscopes. Stethoscopes were obtained from healthcare providers after routine use during an inpatient examination and were randomized to control (no intervention) or ABHR disinfection (2 pumps applied to tubing and bell or diaphragm by study personnel, then allowed to dry). Cultures of the tubing and bell or diaphragm were obtained with premoistened cellulose sponges. Sponges were combined with 1% Tween20-PBS and mixed in the Seward Stomacher. The homogenate was centrifuged and all but ~5 mL of the supernatant was discarded. Samples were plated on sheep’s blood agar and selective media for clinically important pathogens (CIPs) including S. aureus, Enterococcus spp, and gram-negative bacteria (GNB). CFU count was determined by counting the number of colonies on each plate and using dilution calculations to calculate the CFU of the original ~5 mL homogenate. Results: In total, 80 stethoscopes (40 disinfection, 40 control) were sampled from 46 physicians (MDs) and MD students (57.5%), 13 advanced practice providers (16.3%), and 21 nurses (RNs) and RN students (26.3%). The median CFU count was ~30-fold lower in the disinfection arm compared to control (106 [IQR, 50–381] vs 3,320 [986–4,834]; P < .0001). The effect was consistent across provider type, frequency of recent usual stethoscope cleaning, age, and status of pet ownership (Fig. 1). Overall, 26 of 80 (33%) of stethoscopes harbored CIP. The presence of CIP was lower but not significantly different for stethoscopes that underwent disinfection versus controls: S. aureus (25% vs 32.5%), Enterococcus (2.5% vs 10%), and GNB (2.5% vs 5%). Conclusions: Stethoscopes may serve as vectors for clean hands to become recontaminated immediately prior to performing patient care activities. Using ABHR to clean stethoscopes after every use is a practical and effective strategy to reduce overall bacterial contamination that can be easily incorporated into clinical workflow. Larger studies are needed to determine the efficacy of ABHR at removing CIP from stethoscopes as stethoscopes in both arms were frequently contaminated with CIP. Prior cleaning of stethoscopes on the study day did not seem to impact contamination rates, suggesting the impact of alcohol foam disinfection is short-lived and may need to be repeated frequently (ie, after each use).Funding: NoneDisclosures: NoneDisclosures: NoneFunding: None

scholarly journals Long-Term Tacrolimus Blood Trough Level and Patient Survival in Adult Liver Transplantation

2021 ◽  
Vol 11 (2) ◽  
pp. 90
Author(s):  
Chih-Yang Hsiao ◽  
Ming-Chih Ho ◽  
Cheng-Maw Ho ◽  
Yao-Ming Wu ◽  
Po-Huang Lee ◽  
...  
Keyword(s):  
Patient Survival ◽  
Trough Level ◽  
Medical Center ◽  
Term Survival ◽  
Blood Concentrations ◽  
Long Term Survival ◽  
Tacrolimus Level ◽  
Cox's Model ◽  
The Impact

Tacrolimus is the most widely used immunosuppressant in liver transplant (LT) patients. However, the ideal long-term target level for these patients is unknown. This retrospective study aimed to investigate the impact of tacrolimus blood concentration five years after LT on long-term patient survival outcomes in adult LT recipients. Patients who underwent LT between January 2004 and July 2014 at a tertiary medical center were included in this study (n = 189). The mean tacrolimus blood concentrations of each patient during the fifth year after LT were recorded and the overall survival rate was determined. A multivariate analysis of factors associated with long-term survival was conducted using a Cox’s model. The median follow-up period was 9.63 years, and 144 patients (76.2%) underwent live donor LT. Sixteen patients died within 5 years of LT. In the Cox’s model, patients with a mean tacrolimus blood trough level of 4.6–10.2 ng/mL had significantly better long-term survival than those with a mean tacrolimus blood trough level outside this range (estimated hazard ratio = 4.76; 95% confidence interval: 1.34–16.9, p = 0.016). Therefore, a tacrolimus level no lower than 4.6 ng/mL would be recommended in adult LT patients.

scholarly journals Communications and Screening for 2019 Novel Coronavirus at a Tertiary-Care Medical Center

2020 ◽  
Vol 41 (S1) ◽  
pp. s84-s84
Author(s):  
Lorinda Sheeler ◽  
Mary Kukla ◽  
Oluchi Abosi ◽  
Holly Meacham ◽  
Stephanie Holley ◽  
...  
Keyword(s):  
Screening Tool ◽  
Medical Center ◽  
Academic Medical Center ◽  
Tertiary Care ◽  
The United States ◽  
World Health ◽  
Communication Campaign ◽  
Electronic Screening ◽  
Novel Coronavirus ◽  
The Impact

Background: In December of 2019, the World Health Organization reported a novel coronavirus (severe acute respiratory coronavirus virus 2 [SARS-CoV-2)]) causing severe respiratory illness originating in Wuhan, China. Since then, an increasing number of cases and the confirmation of human-to-human transmission has led to the need to develop a communication campaign at our institution. We describe the impact of the communication campaign on the number of calls received and describe patterns of calls during the early stages of our response to this emerging infection. Methods: The University of Iowa Hospitals & Clinics is an 811-bed academic medical center with >200 outpatient clinics. In response to the coronavirus disease 2019 (COVID-19) outbreak, we launched a communications campaign on January 17, 2020. Initial communications included email updates to staff and a dedicated COVID-19 webpage with up-to-date information. Subsequently, we developed an electronic screening tool to guide a risk assessment during patient check in. The screening tool identifies travel to China in the past 14 days and the presence of symptoms defined as fever >37.7°C plus cough or difficulty breathing. The screening tool was activated on January 24, 2020. In addition, university staff contacted each student whose primary residence record included Hubei Province, China. Students were provided with medical contact information, signs and symptoms to monitor for, and a thermometer. Results: During the first 5 days of the campaign, 3 calls were related to COVID-19. The number of calls increased to 18 in the 5 days following the implementation of the electronic screening tool. Of the 21 calls received to date, 8 calls (38%) were generated due to the electronic travel screen, 4 calls (19%) were due to a positive coronavirus result in a multiplex respiratory panel, 4 calls (19%) were related to provider assessment only (without an electronic screening trigger), and 2 calls (10%) sought additional information following the viewing of the web-based communication campaign. Moreover, 3 calls (14%) were for people without travel history but with respiratory symptoms and contact with a person with recent travel to China. Among those reporting symptoms after travel to China, mean time since arrival to the United States was 2.7 days (range, 0–11 days). Conclusion: The COVID-19 outbreak is evolving, and providing up to date information is challenging. Implementing an electronic screening tool helped providers assess patients and direct questions to infection prevention professionals. Analyzing the types of calls received helped tailor messaging to frontline staff.Funding: NoneDisclosures: None

Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (11) ◽  
pp. 2268-2272 ◽  
Author(s):  
YI YOU ◽  
ZHE WANG ◽  
GUO-HONG DENG ◽  
YI LIU ◽  
FEI HAO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Functional Evaluation ◽  
Reporter System ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear

Objective.Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the −262A/T and −188A/G polymorphisms of SLAM in Chinese patients with SLE.Methods.Genotyping of −262A/T (rs2295614) and −188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction.Results.Frequencies of −262A allele and −188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152–1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in −262A-188G haplotype homozygotes compared with −262A-188G heterozygotes and individuals with other genotypes.Conclusion.Our findings suggest that −262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.

scholarly journals The nuclear factor κB inhibitor (E)-2-fluoro-4′-methoxystilbene inhibits firefly luciferase

2012 ◽  
Vol 32 (6) ◽  
pp. 531-537 ◽  
Author(s):  
Albert Braeuning ◽  
Silvia Vetter
Keyword(s):  
Photon Emission ◽  
Gene Promoter ◽  
Firefly Luciferase ◽  
Nuclear Factor Κb ◽  
Signalling Pathway ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Reporter System ◽  
Reporter Assays

Photinus pyralis (firefly) luciferase is widely used as a reporter system to monitor alterations in gene promoter and/or signalling pathway activities in vitro. The enzyme catalyses the formation of oxyluciferin from D-luciferin in an ATP-consuming reaction involving photon emission. The purpose of the present study was to characterize the luciferase-inhibiting potential of (E)-2-fluoro-4′-methoxystilbene, which is known as a potent inhibitor of the NF-κB (nuclear factor κB) signalling pathway that is used to modulate the NF-κB signalling pathway in vitro. Results show that (E)-2-fluoro-4′-methoxystilbene effectively inhibits firefly luciferase activity in cell lysates and living cells in a non-competitive manner with respect to the luciferase substrates D-luciferin and ATP. By contrast, the compound has no effect on Renilla and Gaussia luciferases. The mechanism of firefly luciferase inhibition by (E)-2-fluoro-4′-methoxystilbene, as well as its potency is comparable to its structure analogue resveratrol. The in vitro use of trans-stilbenes such as (E)-2-fluoro-4′-methoxystilbene or resveratrol compromises firefly luciferase reporter assays as well as ATP/luciferase-based cell viability assays.

scholarly journals The Impact of Enhanced Antimicrobial Stewardship Support on Antibiotic Starts in Long-Term Care Facilities

2020 ◽  
Vol 41 (S1) ◽  
pp. s527-s527
Author(s):  
Gabriela Andujar-Vazquez ◽  
Kirthana Beaulac ◽  
Shira Doron ◽  
David R Snydman
Keyword(s):  
Public Health ◽  
Pilot Study ◽  
Infection Control ◽  
Antimicrobial Stewardship ◽  
Long Term Care ◽  
Medical Center ◽  
Term Care ◽  
Care Facilities ◽  
The Impact

Background: The Tufts Medical Center Antimicrobial Stewardship (ASP) Team has partnered with the Massachusetts Department of Public Health (MDPH) to provide broad-based educational programs (BBEP) to long-term care facilities (LTCFs) in an effort to improve ASP and infection control practices. LTCFs have consistently expressed interest in individualized and hands-on involvement by ASP experts, yet they lack resources. The goal of this study was to determine whether “enhanced” individualized guidance provided by an ASP expert would lead to antibiotic start decreases in LTCFs participating in our pilot study. Methods: A pilot study was conducted to test the feasibility and efficacy of providing enhanced ASP and infection control practices to LTCFs. In total, 10 facilities already participating in MDPH BBEP and submitting monthly antibiotic start data were enrolled, were stratified by bed size and presence of dementia unit, and were randomized 1:1 to the “enhanced” group (defined as reviewing protocols and antibiotic start cases, providing lectures and feedback to staff and answering questions) versus the “nonenhanced” group. Antibiotic start data were validated and collected prospectively from January 2018 to July 2019, and the interventions began in April 2019. Due to staff turnover and lack of engagement, intervention was not possible in 2 of the 5 LTCFs randomized to the enhanced group, which were therefore analyzed as a nonenhanced group. An incidence rate ratios (IRRs) with 95% CIs were calculated comparing the antibiotic start rate per 1,000 resident days between periods in the pilot groups. Results: The average bed sizes for enhanced groups versus nonenhanced groups were 121 (±71.0) versus 108 (±32.8); the average resident days per facility per month were 3,415.7 (±2,131.2) versus 2,911.4 (±964.3). Comparatively, 3 facilities in the enhanced group had dementia unit versus 4 in the nonenhanced group. In the per protocol analysis, the antibiotic start rate in the enhanced group before versus after the intervention was 11.35 versus 9.41 starts per 1,000 resident days (IRR, 0.829; 95% CI, 0.794–0.865). The antibiotic start rate in the nonenhanced group before versus after the intervention was 7.90 versus 8.23 antibiotic starts per 1,000 resident days (IRR, 1.048; 95% CI, 1.007–1.089). Physician hours required for ASP for the enhanced group totaled 8.9 (±2.2) per facility per month. Conclusions: Although the number of hours required for intervention by an expert was not onerous, maintaining engagement proved difficult and in 2 facilities could not be achieved. A statistically significant 20% decrease in the antibiotic start rate was achieved in the enhanced group after interventions, potentially reflecting the benefit of enhanced ASP support by an expert.Funding: This study was funded by the Leadership in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) fellowship training grant award from the CDC.Disclosures: None

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