Graf, Erin H.

AbstractEmbolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic‐liquid‐based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X‐ray visibility, and cytotoxicity. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non‐survival and survival porcine experiments, successful PVE is achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug‐resistant patient‐derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.

Abstract Background In 2021, the state of Arizona experienced the largest focal outbreak of West Nile virus (WNV) in US history. Timely and accurate diagnostic testing remains a challenge for WNV due to transient viremia and limited immunoassay specificity. Recent studies have identified whole blood (WB) and urine as more sensitive specimen types for the detection of WNV RNA. Methods We evaluated ordering practices, test performance, and patient characteristics of probable and confirmed cases. In total, we identified 190 probable and proven cases, including 127 patients (66.8%) with neuroinvasive disease. Results Among all cases, only 29.5% had WNV polymerase chain reaction (PCR) testing ordered on WB, of which 80.3% resulted as positive, including 7 cases in which WNV serologic testing was negative and 5 cases for which serologic testing was not ordered. In comparison, only 23.7% of cases that had cerebrospinal fluid (CSF) PCR ordered had a positive result, including 3 cases that were negative by PCR on WB. In contrast, WNV PCR on WB detected 12 neuroinvasive cases that were CSF PCR negative. WNV PCR testing in urine was only ordered on 2 patients, both of whom were positive. Crossing cycle threshold (Ct) values were not significantly different between WB and CSF specimen types, nor was there a correlation between Ct value and days from symptom onset at the time of sample collection; all specimen types and time points had Ct values, with 98% above 30. WB was positive by WNV PCR in several patients for >7 days (range, 7–25 days) after symptom onset, as was the CSF PCR. Conclusions Taken together, these findings indicate that WNV PCR testing on WB may be the best initial test for timely diagnosis of WNV infection, irrespective of clinical manifestation; however, if negative in patients with suspected neuroinvasive disease, WNV PCR testing on CSF should be ordered.

A woman in her 50s presented with a 4-day history of left knee pain, erythema, swelling as well as malaise and rigours 1 month after undergoing a left knee meniscectomy. She was diagnosed with left native knee septic arthritis and underwent arthroscopic irrigation and debridement of the knee; cultures from synovial tissue grew Rhodococcus erythropolis. Rhodococcus spp are soil-dwelling and livestock-dwelling bacteria which occasionally cause disease in immunocompromised hosts. Infection in immunocompetent hosts is rare, and septic arthritis secondary to Rhodococcus erythropolis has not been reported previously.

Abstract Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter‐directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non‐survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans‐arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient‐derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo‐ and immunotherapy response in solid tumors.

Abstract Introduction/Objective Our laboratory implemented a full COPAN WASPLab microbiology automation line in March of 2023. Prior to this implementation, our laboratory routinely observed potential bacterial contamination of sterile specimens, as well as culture plates in which the specimens were not struck out, due to a large number of new staff members and heavy workloads. Both of these quality issues directly impact patient care due to potential misleading or delayed results. We hypothesized that automation of the plating and incubation steps would reduce both of these quality issues significantly. Methods/Case Report Potential contamination and plates not struck were self-reported by technologists during pre- implementation (July 2022-Feb 2023) and post-implementation (Mar-Apr 2023) periods. Potential contamination was defined as one or two colonies of bacteria on a single agar plate, consistent with skin fora, from a normally sterile source specimen and reviewed by the Director for potential clinical correlation. Plates unstruck in the post- implementation period continued to include those manually set up. A 2 two proportion z-test was performed to compare pre and post implementation data. Results (if a Case Study enter NA) A total of 3,055 and 1,750 sterile source cultures were analyzed in the pre- and post-implementation periods, respectively. Of these, 109 versus 8 were designated as potential contamination, respectively, resulting in a significant reduction (Z stat 6.7, p<0.0001). For the plate streaking portion, 22,814 and 7,211 cultures were analyzed in the pre- and post-implementation periods, respectively. Of these, 21 versus 3 plates were not struck, respectively, resulting in a greater than 2-fold reduction per culture, but did not meet significance. Conclusion Implementation of microbiology automation significantly reduced skin flora contamination of sterile source cultures. Proportions of unstruck plates were also reduced, although these did not meet significance, likely due to the low numbers.

Abstract Introduction/Objective In January of 2021 our laboratory experienced the occupational exposure of 3 technologists to the select agent Burkholderia pseudomallei due to improper recognition and manipulation outside a biosafety cabinet. Subsequently, an interactive computer module was created to train technologists on timely recognition, followed by a “fake” patient test to evaluate comprehension. In that initial period, 100% compliance and successful recognition was demonstrated. To evaluate sustained compliance and recognition, another wave of evaluation was performed Jan- Dec 2022. Methods/Case Report During the study period several new staff members were hired and demonstrated compliance with completing the computer module. Clinical isolates suspicious for a select agent were reported to the Medical Director on rounds daily and reviewed for potential exposure, which was defined as manipulation of the suspicious isolate outside of the biosafety cabinet. Additional challenge “fake” patients were circulated. Results (if a Case Study enter NA) During the study period, 16 isolates were deemed suspicious for select agents based on macroscopic and microscopic morphology and biochemical reactions. Of these, 0 resulted in laboratory exposures. Of the challenge isolates, 1 resulted in a near-miss potential for exposure due to the lack of recognition of macroscopic characteristics. Conclusion The use of an interactive computer module focused around timely recognition and safe handling of potential select agents resulted in sustained laboratory safety and avoidance of potential occupational exposures.

Abstract Background The BioFire® FilmArray® Gastrointestinal Pathogen Panel (GIPP) tests for 22 potential pathogens in stool, including Clostridioides difficile. C. difficile nucleic acid is detected via nested polymerase chain reaction (PCR) targeting toxin A (TcdA) and/or toxin B (TcdB) genes. While PCR-based diagnostic methods are highly sensitive, they lack specificity to differentiate colonization from C. difficile infection (CDI). Mayo Clinic Arizona (MCA) uses enzyme immunoassay (EIA) testing for toxin A/B and glutamate dehydrogenase antigens with reflex to PCR for discordance as the primary algorithm for diagnosing CDI; however, GIPP PCR testing circumvents this algorithm. When used in patients with low pretest probability for CDI, clinical false positives can lead to inappropriate diagnosis and treatment of colonization. GIPA Results in the Electronic Medical Record Pre-Intervention MCA Standalone C. difficile Testing Algorithm Abbreviations – EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test Methods We convened a multidisciplinary quality improvement team to reduce the detection and treatment of C. difficile colonization secondary to GIPP test results. Surveys were sent to providers and nurses as part of a formal gap analysis and included questions around ordering patterns, knowledge of appropriate tests, and associated costs. Baseline data was compiled from GIPP orders in MCA from 1/1/2022-9/30/2022. Results There were 1978 GIPP orders for 1694 patients during the study period (∼7 GIPPs/day). Most orders (65%) originated from ambulatory settings. The most common positive target was C. difficile (355/723, 49%), which resulted in treatment for suspected CDI in 94.9% (337/355) of cases. Of the 49 providers who responded to the survey, 86% ordered the GIPP at least monthly. Testing for C. difficile was the 2nd most common reason for ordering the GIPP. Most providers underestimated the cost of the panel and were unfamiliar with the differences between the GIPP and EIA testing algorithm. Nurses sought clarification on stool samples suitable for GIPP testing. Following education and modifications to ordering in the electronic health record, the decision was made to remove the C. difficile target from the GIPP. Provider Understanding of C. difficile Testing Methods GIPA Results in the Electronic Medical Record Post-Intervention Conclusion Multiplex PCR panels are comprehensive but require careful implementation to facilitate diagnostic stewardship. Facilities with robust standalone C. difficile testing algorithms may consider removing the C. difficile target from the GIPP. Disclosures All Authors: No reported disclosures