Infective endocarditis is rare in patients with hematologic malignancy and neutropenia.

BACKGROUND: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. METHODS: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT). RESULTS: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. CONCLUSIONS: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.

Current practices and evaluation of barriers and facilitators to surgical site infection prevention measures in Jimma, Ethiopia.

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.

Loss of synergistic transcriptional feedback loops drives diverse B-cell cancers.

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.