Objective We developed a push notification allowing for an electronic acknowledgment of critical lab results to providers in the intensive care unit. Materials and Methods This project was conducted over a 3-month period at a large academic safety net hospital. A push notification and acknowledgment system were created to comply with the existing critical results notification requirements. We monitored the number of acknowledged results, time to acknowledgment, and lab type. Results Prior to the push notification, lab services paged the provider. This resulted in many critical lab results relayed to the clinician beyond the expected 10-minute window. With the push notification workflow, we found that, during the 3-month period, 82, or 5.8%, of the 1414 results were acknowledged. This represented 82 less pages/calls lab services had to make. Discussion The push notification alert was easy to use and there was quicker results notification when acknowledged. There were limitations due to hand-offs for clinicians and some were not familiar with the mobile technology and the electronic acknowledgment. Conclusions Although the acknowledgment rate was low, every electronic acknowledgment saved lab service technicians an average of 10 minutes compared to the existing workflow. As familiarity with the technology and workflow increases, this novel form of communication has the potential to have significant cost savings for lab services, in addition to efficiency gains for lab, clinicians, and more timely care. The integration of health information technology and push notification of critical labs should be the focus of investigation for further future research.

No abstract

Although KIT mutations are present in 20-25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

We have used Epstein-Barr virus (EBV) infection in vitro to delineate two distinct stages in B cell activation. Previous studies have shown that the BLAST-2 (EBVCS) (EBV cell surface) activation antigen is expressed on a small fraction of B cells within 24 h of stimulation with a variety of agents, including mitogens and EBV. In this study, we have been able to isolate the BLAST-2 (EBVCS)+ cells early after activation/infection with EBV. These cells are small B cells that are actively synthesizing RNA but not DNA, and are, therefore, clearly distinct from large proliferating lymphoblasts. In addition, they contain multiple copies of the EBV genome, express the viral nuclear antigen (EBNA) and, most importantly, proceed to undergo transformation when placed back in culture. By comparison, the BLAST-2 (EBVCS)- population does not undergo transformation even though fraction of these cells are activated for RNA synthesis and express EBNA. Thus, using the EBV system, we have been able to show directly that an activated B cell first expresses the BLAST-2 (EBVCS) antigen concomitant with an increase in RNA synthesis, and then subsequently proceeds to differentiate into a proliferating lymphoblast.

Reported herein is a case of composite small lymphocytic lymphoma (SLL) and extramedullary myeloid tumor (EMT) occurring in the same lymph node. Routine morphologic examination revealed a diffuse proliferation of small mature lymphocytes with numerous irregularly dispersed nodules, closely resembling SLL with prominent proliferation centers or Richter's transformation. Flow cytometric immunophenotyping and immunohistochemical stains demonstrated the presence of SLL cells as well as myeloblasts, confirming the diagnosis of a composite SLL and EMT. Conventional cytogenetics and fluorescence in situ hybridization studies revealed inversion 16 chromosome involving the core binding factor beta and myosin heavy chain 11 genes, characteristic of acute myeloid leukemia with abnormal bone marrow eosinophils and inv(16) or t(16;16) [CBFbeta/MYH11]. In conclusion, the occurrence of SLL and EMT in the same lymph node is rare and multiparameter approach is essential for a definitive diagnosis.

Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma in the United States. DLBCL comprises biologically distinct subtypes including germinal center-like (GCB) and activated-B-cell-like DLBCL (ABC). The most aggressive type, ABC-DLBCL, displays dysregulation of both canonical and noncanonical NF-κB pathway as well as genomic instability. Although, much is known about the tumorigenic roles of the canonical NF-kB pathway, the precise role of the noncanonical NF-kB pathway remains unknown. Here we show that activation of the noncanonical NF-κB pathway regulates chromosome stability, DNA damage response and centrosome duplication in DLBCL. Analysis of 92 DLBCL samples revealed that activation of the noncanonical NF-κB pathway is associated with low levels of DNA damage and centrosome amplification. Inhibiting the noncanonical pathway in lymphoma cells uncovered baseline DNA damage and prevented doxorubicin-induced DNA damage repair. In addition, it triggered centrosome amplification and chromosome instability, indicated by anaphase bridges, multipolar spindles and chromosome missegregation. We determined that the noncanonical NF-κB pathway execute these functions through the regulation of GADD45α and REDD1 in a p53-independent manner, while it collaborates with p53 to regulate cyclin G2 expression. Furthermore, this pathway regulates GADD45α, REDD1 and cyclin G2 through direct binding of NF-κB sites to their promoter region. Overall, these results indicate that the noncanonical NF-κB pathway plays a central role in maintaining genome integrity in DLBCL. Our data suggests that inhibition of the noncanonical NF-kB pathway should be considered as an important component in DLBCL therapeutic approach.

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.