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Objective: This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu ), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations., Materials and Methods: PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically., Results: At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB's interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API., Discussion: An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology., Conclusion: The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API., (© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Objectives: CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia chromosome translocation (Ph); BCR-ABL1 rearrangement in B lymphoblastic leukemia/lymphoma (B-LL). However, the significance of CD25 expression in Ph negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is largely unknown., Methods: CD25 expression by flow cytometry (FC) was correlated with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29 marrow measured by FC in the context of cytogenetic risk stratification in Ph- patients., Results: CD25 expression was greater in Ph positive (Ph+) patients (80%) than in Ph- patients (17%), predicting Ph+ with 80% sensitivity and 86% specificity. In Ph- patients, CD25 expression (in 14 patients, 16%) was associated with RD in the cytogenetic intermediate-risk group: detectable RD in 50% of CD25+ patients vs 14% of CD25- patients. Interestingly, one CD25+/Ph- patient had a Ph-like genotype ( ZC3HAV1-ABL2 rearrangement), and another had dual MYC-IGH and BCL2-IGH rearrangements., Conclusions: Our findings not only confirm the predictive power of CD25 expression for Ph+ but also demonstrate that CD25 expression is associated with RD (a biomarker correlated with prognosis) in Ph- patients. The latter finding is likely associated with underlying molecular abnormalities, including Ph-like genotype., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: To evaluate the effectiveness of prospective review of orders for fresh-frozen plasma (FFP) and platelets in reducing blood-product use, and of the effectiveness of preparing pathology residents to serve as clinical consultants., Design: At our 572-bed tertiary-care hospital, we developed guidelines for the use of blood products in collaboration with a variety of departments. For patients whose condition(s) met generally accepted criteria, we identified trigger points to allow for quick release by blood bank staff of blood products. For patients whose condition(s) did not meet the applicable criteria, the on-call pathology resident reviewed the medical record of that patient to determine whether there were any extenuating circumstances; consulted with the ordering physician and attending pathologist, as needed; and advised the house staff on appropriate use of blood products. We evaluated the change in use of blood products between the years 2009 and 2012 to assess the effectiveness of the program., Results: We observed a decrease of 38.8% and 31.4% in the use of FFP and platelets, respectively (29.7% and 21.1%, respectively, when normalized for the number of discharges). If projected to the national level, this improvement would translate to an annual cost reduction of approximately $130 million., Conclusions: Prospective review of orders for blood products can significantly improve use of these products, thereby reducing risk to patients and avoiding unnecessary healthcare costs. The involvement of pathology residents in the prospective review process provides an excellent opportunity for their training as laboratory consultants., (Copyright© by the American Society for Clinical Pathology (ASCP).)

Screening for monoclonal gammopathies is usually done by serum protein electrophoresis (SPEP) and serum free light chain tests. SPEP may be followed by immunofixation electrophoresis (IFE). IFE may be ordered by the treating physician or be at the discretion of the pathologist. We examined the appropriateness of IFE ordering by treating physicians and report on our findings, follow-up changes to the ordering process, and results of the change. We retrospectively analyzed the data from our laboratory from April 2009 through July 2012. In April 2009, 3 options for test ordering were available for the clinicians: SPEP with reflex IFE, SPEP only, and SPEP with IFE. This test ordering option was limited to SPEP with reflex IFE only in April 2010. We compared the rates of SPEP and IFE performed in the 2 periods (ie, April 2009 through April 2010 and May 2010 through July 2012). There was a substantial drop in the IFE/SPEP ratio from 0.47 to 0.21. Review of electronic medical records by the consultant pathologist was instrumental in improving the utilization and enhancing the value of pathology consultation. Possible impacts on laboratory costs, revenue, and overall health care are also presented.