Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.

MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type-specific enhancer leads to increased MYC expression.

The financial and environmental impact of unopened medical supplies discarded in the emergency department.

Background: Inefficient supply chain management within the US healthcare industry results in significant financial and environmental impact. Unopened medical supplies may routinely be discarded in the Emergency Department (ED), contributing as a source of unnecessary medical waste.

Objectives: Quantify the financial and environmental impact of unopened medical supplies that are routinely discarded in two EDs.

The Climate Impact of Medical Residency Interview Travel in the United States and Canada: A Scoping Review.

The change from in-person to virtual interviews for graduate medical education (GME) provides the opportunity to compare the potential environmental effects. To explore and summarize the existing literature on the potential climate impact of medical residency interview travel through a scoping review. The search was conducted in October 2022 using 5 research databases.

PCNEO, a New Proficiency Testing Program for Flow Cytometric Analysis of Plasma Cell Neoplasms From the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee.

Context.—: In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program-PCNEO-to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group.

Objective.

Heterogeneity of B cell lymphopoiesis in patients with premalignant and active myeloma.

To better characterize the heterogeneity of multiple myeloma (MM), we profiled plasma cells (PCs) and their B cell lymphopoiesis in the BM samples from patients with monoclonal gammopathy of undetermined significance, smoldering MM, and active MM by mass cytometry (CyTOF) analysis. Characterization of intra- and interneoplastic heterogeneity of malignant plasmablasts and PCs revealed overexpression of the MM SET domain (MMSET), Notch-1, and CD47. Variations in upregulation of B cell signaling regulators (IFN regulatory factor 4 [IRF-4], CXCR4, B cell lymphoma 6 [Bcl-6], c-Myc, myeloid differentiation primary response protein 88 [MYD88], and spliced X box-binding protein 1 [sXBP-1]) and aberrant markers (CD319, CD269, CD200, CD117, CD56, and CD28) were associated with different clinical outcomes in clonal PC subsets.

Non-Hodgkin lymphoma mimicking acute leukemia: a report of six cases and review of the literature.

Aggressive subtypes of non-Hodgkin lymphoma may uncommonly be referred to clinical oncologists for treatment of acute leukemia, due to an elevated or rapidly rising white blood cell count (WBC), with circulating neoplastic cells that morphologically resemble leukemic blasts seen in acute myeloid or lymphoblastic leukemia. We describe six cases of non-Hodgkin lymphoma that mimicked acute leukemia and were identified in the pathology records of the Brigham and Women's Hospital. The patients were older adults (mean age 70 years), who presented with leukocytosis (mean 79.

Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma.

Oncogenic activated RAS mutations have been detected in 50% of de novo and 70% of relapsed multiple myeloma (MM) patients. Translocation t(11;14) involving IgH/CCDN1 and overexpression of cyclin-Ds are early events in MM pathogenesis, enhancing uncontrolled MM cell growth. We hypothesized that targeting both RAS/MAPK pathway molecules including Erk1/2 along with cyclin-Ds enhances MM cytotoxicity and minimizes side effects.

Impact of sickle cell trait on morbidity and mortality from SARS-CoV-2 infection.

The COVID-19 pandemic has highlighted racial health disparities within the United States. Although social determinants of health are the most likely drivers of this disparity, it is possible that genetic traits enriched in the black population like sickle cell trait (SCT) could worsen the morbidity and mortality of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients admitted for SARS-CoV-2 infection who identified as black or African American were included in the study (n = 166).

Laboratory Workup of Lymphoma in Adults.

Objectives: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings.

Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists.

Context.—: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice.

Participation in the College of American Pathologists Laboratory Accreditation Program Decreases Variability in B-Lymphoblastic Leukemia and Plasma Cell Myeloma Flow Cytometric Minimal Residual Disease Testing: A Follow-up Survey.

Context.—: Minimal residual disease (MRD) testing by flow cytometry is ubiquitous in hematolymphoid neoplasm monitoring, especially B-lymphoblastic leukemia (B-ALL), for which it provides predictive information and guides management. Major heterogeneity was identified in 2014.

"Meds-in-Hand" Intervention to Reduce Critical Process Delays in Pediatric Human Immunodeficiency Virus Post-Exposure Prophylaxis.

Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention.

High-risk Pediatric Emergencies.

More than half of pediatric malpractice cases arise from emergency departments, primarily due to missed or delayed diagnoses. All providers who take care of children in emergency departments should be aware of this risk and the most common diagnoses associated with medicolegal liability. This article focuses on diagnosis and management of high-risk diagnoses in pediatric patients presenting to emergency departments, including meningitis, pneumonia, appendicitis, testicular torsion, and fracture.

Identifying a Golden Opportunity: Adolescent Interest in Contraceptive Initiation in a Pediatric Emergency Department.

Contraception use reduces teen pregnancy, and long-acting reversible contraception is recommended as first-line treatment. Since many adolescents use the emergency department (ED) as a primary source of health care, it is a potential site of contraceptive counseling and provision. We surveyed female adolescents to assess desire for contraceptive counseling and initiation/change during an ED visit.