Background The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping “cell-of-origin”. Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry. Methods We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using >325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and genome copy number (microarrays). Findings From the resulting data, we identified gains in active chromatin in enhancers/super-enhancers that likely promote unchecked B-cell receptor signaling, including one we validated near the immunoglobulin superfamily receptors FCMR and PIGR . More striking and pervasive was the profound loss of key B-cell identity TFs, tumor suppressors and their super-enhancers, including EBF1, OCT2 ( POU2F2 ), and RUNX3 . Using a novel approach to identify transcriptional feedback, we showed that these core transcriptional circuitries are self-regulating. Their selective gain and loss form a complex, iterative, and interactive process that likely curbs B-cell maturation and spurs proliferation. Interpretation Our study is the first to map the transcriptional circuitry of the most common blood cancers. We demonstrate that a critical subset of B-cell TFs and their cognate enhancers form self-regulatory transcriptional feedback loops whose disruption is a shared mechanism underlying these diverse subtypes of B-cell lymphoma. Funding National Institute of Health, Siteman Cancer Center, Barnes-Jewish Hospital Foundation, Doris Duke Foundation.

Objective: Surgical site infections (SSIs) greatly burden healthcare systems around the world, particularly in low- and middle-income countries. We sought to employ the Systems Engineering Initiative for Patient Safety (SEIPS) model to better characterize SSI prevention practices and factors affecting adherence to prevention guidelines at Jimma University Medical Center (JUMC). Design: Our cross-sectional study consisted of semistructured interviews designed to elicit perceptions of and barriers and facilitators to SSI prevention among surgical staff and observations of current preoperative, perioperative, and postoperative SSI prevention practices in surgical cases. Interviews were recorded, manually transcribed, and thematically coded within the SEIPS framework. Trained observers recorded compliance with the World Health Organization’s SSI prevention recommendations. Setting: A tertiary-care hospital in Jimma, Ethiopia. Participants: Surgical nurses, surgeons, and anesthetists at JUMC. Results: Within 16 individual and group interviews, participants cited multiple barriers to SSI prevention including shortages of water and antiseptic materials, lack of clear SSI guidelines and training, minimal Infection Prevention Control (IPC) interaction with surgical staff, and poor SSI tracking. Observations from nineteen surgical cases revealed high compliance with antibiotic prophylaxis (94.7%), hand scrubbing (100%), sterile gloves and instrument use (100%), incision site sterilization (100%), and use of surgical safety checklist (94.7%) but lower compliance with preoperative bathing (26.3%), MRSA screening (0%), and pre- and postoperative glucose (0%, 10.5%) and temperature (57.9%, 47.3%) monitoring. Conclusions: Utilizing the SEIPS model helped identify institution-specific barriers and facilitators that can inform targeted interventions to increase compliance with currently underperformed SSI prevention practices at JUMC.

Background Lack of hand hygiene (HH) amongst healthcare workers (HCWs) contributes to healthcare associated infections and the spread of multidrug-resistant organisms. We assessed HCW HH knowledge, attitudes, and compliance using WHO tools and applied the Systems Engineering Initiative for Patient Safety (SEIPS) model in interviews to help guide and increase sustainability of HH interventions. Methods We conducted a cross-sectional study at Jimma University Medical Center (JUMC) in Jimma, Ethiopia. We assessed HCW’s HH knowledge and attitudes using questionnaires adapted from WHO resources via systematic sampling. Observations of HH practices at WHO’s 5 Moments of HH were conducted by non-identified, trained observers via systematic sampling. 22 semi-structured interviews were conducted via convenience sampling with HCWs using an interview guide based on the SEIPS model. Results We observed 1,386 HH moments and found a compliance rate of 9.38%, with compliance highest after contact with patient surroundings (27.92%) compared to the other four HH moments (1.77 - 9.57%). Of 251 survey participants, 13.6% had prior HH training and 69.9% reported routine HH compliance. The average knowledge score was 61.4%, with no significant difference between participants that identified as trained vs untrained (p=0.41). 68% of interview participants stated they were unaware of JUMC’s Infection Prevention and Control (IPC) team and are more likely to perform HH if a patient appears infectious. Interview participants cited multiple barriers to HH (table 1). Table 1 Conclusion Baseline HH compliance and knowledge were low despite perceived compliance and regardless of prior HH training. Relatively higher compliance after patient contact may be due to perceptions of patient infectiousness. Utilizing the SEIPS model as an adjunct to WHO HH guidelines has provided actionable items upon which the JUMC IPC team can focus to improve HH practices: providing a sustainable supply of alcohol hand rub, ongoing HH education targeting knowledge deficits, and enhanced IPC presence and HH monitoring. Disclosures Meredith Kavalier, MD, University of Wisconsin-Madison Global Health Institute (Grant/Research Support)

Background Infective endocarditis (IE) is a highly morbid complication of blood stream infections (BSIs) involving neutrophil and platelet activation. Patients with hematologic malignancies have frequent BSIs but a low incidence of IE. We sought to evaluate the microbiology of BSIs and rates of IE in hospitalized patients with hematologic malignancies. Methods Patients admitted to the University of Wisconsin Hospital hematology ward between 2018 and 2020 were included if blood cultures obtained grew Streptococcus spp., Staphylococcus spp., Enterococcus spp., Streptococcus-like bacteria, and fungi. Two investigators recorded patient demographics, BSI microbiology, and hospital course. Using the Duke’s criteria each BSI was classified as definite, possible, or rejected cases of IE. Cases of possible IE were reviewed for evidence of missed IE within 90 days of hospital admission based on readmission with repeat positive blood culture and new signs or symptoms of IE. Definite cases were reviewed by two additional investigators to corroborate cases of IE. Results Our study included 101 unique patients with hematologic malignancy: 35.6% female, mean age 58.4, and 10.9% had multiple BSIs during our study period. Of 111 distinct BSIs, 82.6% were neutropenic, 37.4% community acquired, and 21.7% polymicrobial. Of 129 positive blood cultures, 41.0% isolated Streptococcus spp., 5.4% Staphylococcus aureus, 17.8% other Staphylococcal spp., 7% Enterococcus faecalis, 9.3% other Enterococcus spp., 9.3% Gamella spp., and 4.7% Candida spp. Of 111 BSI, 2 were classified as definite cases, 39 as possible, 70 as rejected. After further review, only 1 was considered a true cases of IE and they were not neutropenic. The 90-day survival rate for all patients was 76.2%. Conclusion We found a very low incidence of IE in our study. Low rates of IE in our population aligns with previous reports showing rare cases of IE in neutropenic and malignancy patients with BSIs and raises questions about the utility of invasive IE workups in neutropenic patients with hematologic malignancies. Further studies are needed to identify patient or microbiologic factors that can be used to guide appropriate use of transesophageal echocardiography to evaluate IE in patients with hematologic malignancy. Disclosures All Authors: No reported disclosures.

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