38 research outputs found
Consolidation of P2Y12 Testing While Maintaining Quality and Turnaround Time
Objective:
To consolidate the test performed at 2 different locations at 1, thereby improving cost effectiveness while maintaining quality and result turnaround time.https://jdc.jefferson.edu/patientsafetyposters/1059/thumbnail.jp
Non-Hodgkin and Hodgkin Lymphomas Select for Overexpression of BCLW.
Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an antiapoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other antiapoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of datasets comprising approximately 2,300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as indolent and aggressive lymphomas. Data were validated experimentally with qRT-PCR and IHC. Results: We report BCLW is significantly overexpressed in aggressive and indolent lymphomas, including DLBCL, Burkitt, follicular, mantle cell, marginal zone, and Hodgkin lymphomas. Notably, BCLW was preferentially overexpressed over that of BCL2 and negatively correlated with BCL2 in specific lymphomas. Unexpectedly, BCLW was overexpressed as frequently as BCL2 in follicular lymphoma. Evaluation of all five antiapoptotic BCL2 family members in six types of B-cell lymphoma revealed that BCL2, BCLW, and BCLX were consistently overexpressed, whereas MCL1 and A1 were not. In addition, individual lymphomas frequently overexpressed more than one antiapoptotic BCL2 family member. Conclusions: Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other antiapoptotic BCL2 family members. Our results suggest BCLW may be equally as important in lymphomagenesis as BCL2 and that targeting BCLW in lymphomas should be considered. ©2017 AACR
Is Myeloproliferative Neoplasm with Splanchnic Vein Thrombosis a Distinct Clinical Entity?
Clinical History:
A 29 year-old previously healthy female presented with sub-acute symptoms of weight loss, right upper quadrant pain and nausea.
CBC results: WBC-11.7, Hb- 12.5, Platelet- 286, MCV- 90, MCV- 26.8, RDW- 18%.
Imaging: Ultrasound and MRI of the abdomen were suggestive of Budd-Chiari syndrome that was supported by a liver biopsy showing features of hepatic outflow obstruction(Figure 1). There was no clinical or radiological evidence of splenomegaly. The hypercoagulable work-up was negative. An underlying Myeloproliferative Neoplasm (MPN) was suspected
Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia as a Presenting Feature of Angioimmunoblastic T-Cell Lymphoma (AITL).
Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of the clinical presentation of AITL to enable physicians to more promptly recognize, diagnose and initiate treatment
Is Hemoglobin Variant Analysis Helpful in the Diagnostic Work-up of Patients Revealing Microcytic Erythrocytosis on Complete Blood Count?
Introduction:
Microcytic erythrocytosis is an abnormal CBC (complete blood count) finding that is under-recognized, poorly understood, and consequently under-utilized in patient care. It is characterized by decreased MCV and increased RBC count. Its etiology is likely multifactorial and includes thalassemias and hemoglobinopathies. The focus of our study was to determine the relative prevalence of hemoglobin-associated disorders in patients revealing microcytic erythrocytosis on CBC and to demonstrate whether or not hemoglobin variant analysis should be included in the diagnostic work-up of such cases
BCL-W has a fundamental role in B cell survival and lymphomagenesis.
Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B cell apoptosis. Moreover, Bcl-w loss profoundly delayed MYC-mediated B cell lymphoma development due to increased MYC-induced B cell apoptosis. We also determined that MYC regulates BCL-W expression through its transcriptional regulation of specific miR. BCL-W expression was highly selected for in patient samples of Burkitt lymphoma (BL), with 88.5% expressing BCL-W. BCL-W knockdown in BL cell lines induced apoptosis, and its overexpression conferred resistance to BCL-2 family-targeting BH3 mimetics. Additionally, BCL-W was overexpressed in diffuse large B cell lymphoma and correlated with decreased patient survival. Collectively, our results reveal that BCL-W profoundly contributes to B cell lymphoma, and its expression could serve as a biomarker for diagnosis and aid in the development of better targeted therapies
Durable Response to Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, and Prednisone (BV-CHP) in a Patient with CD30-Positive PTCL Arising as a Post-Transplant Lymphoproliferative Disorder (PTLD)
T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. Herein we report a case of CD30-positive T-cell PTLD that was successfully treated with BV-CHP, suggesting the added value of the addition of BV to chemotherapy, contributing to our patient\u27s long and ongoing progression-free survival. To our knowledge, this is the first documented case of successful treatment using BV-CHP for a CD30-positive, EBV-negative, late T-cell PTLD
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
Aplastic Anemia Post Liver Transplant Due to Graft-versus-host Disease
Poster presented at: American society for clinical pathology (ASCP) conference 2012, Boston MA, USA.
Introduction:
The patient was a 64-year-old male presented with a 2 day history of increasing fevers and altered mental status. He underwent orthotopic liver transplant for cryptogenic cirrhosis, probably secondary to non-alcoholic steatohepatitis, 45 days before. The head and neck imaging showed pancytopenia with WBC 0.6 x 109 /L., hemoglobin 6.8 g/dl and platelet 29 x 109 /L