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Introduction: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non‐monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B‐ALL; referred to as B/myeloid MPALisoMPO) in adult patients is unknown. Methods: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPALisoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B‐ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. Results: Cases of B/myeloid MPALisoMPO showed a fairly homogenous single B‐lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPALisoMPO. B/myeloid MPALisoMPO patients had similar overall and leukemia free survivals as B‐ALL patients and better than other MPAL patients. Conclusion: This is the first study to investigate the clinical significance of adult B/myeloid MPALisoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPALisoMPO clinically behaves more similarly to B‐ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes. [ABSTRACT FROM AUTHOR]

Happiness is a positive internal experience and an indicator of mental health. Having happy and efficient employees is one of the ideals of healthcare organizations, given its impact on the quality of healthcare services. Emergency healthcare staff members face various unpleasant and stressful events. It has been suggested that fragrant herbs such as Citrus aurantium can have cheerfulness effects on individuals. Therefore, this study was conducted to investigate the effect of Citrus aurantium aroma on the happiness of pre-hospital emergency staff. A randomized placebo controlled clinical trial was carried out on 167 prehospital emergency medical staff who were randomly assigned into two groups of aromatherapy and placebo. The participants received Citrus aurantium aromatherapy and placebo for five work shifts and for two consecutive weeks. Aromatherapy was performed using 10% Citrus aurantium scent applied via a pendant containing 1.5 cc of Citrus aurantium scent. The distance from the nose to the container was about 20 cm with the neck straight and the head in a balanced position. Data regarding staff happiness were collected using the Oxford Happiness Questionnaire, which were analyzed using descriptive and inferential statistics. The mean level of happiness did not differ between the intervention and control groups (p = 0.99). Work experience had a statistically significant inverse association with happiness (coefficient = −0.76, 95% CI: −1.49, −0.03). The findings of this randomized controlled trial indicate that Citrus aurantium aroma has no effect on the happiness of prehospital emergency medical services workers. There is a need to study the effect of a combination of complementary and alternative methods on the creation of positive psychological feelings among pre-hospital emergency staff. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease. [ABSTRACT FROM AUTHOR]

Ewing's sarcoma is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases ( P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ewing's sarcoma family tumors are aggressive small round cell malignancies that arise in bone or soft tissues in adolescents and young adults. The addition of chemotherapy to local control measures has remarkably improved the survival of patients with localized disease. However, metastatic tumors are often refractory to conventional chemotherapy and irradiation, and the outcome of patients with metastatic or recurrent disease remains dismal. Despite growing understanding of the molecular biology of this tumor and the discovery of new therapeutic targets such as the insulin growth factor-1 receptor, tumor resistance continues to be a formidable challenge. Numerous adaptive mechanisms have been identified which allow tumor cells to escape the cytotoxic effect of chemotherapeutic agents. This review focuses on these mechanisms in an effort to highlight opportunities for more effective disease control. [ABSTRACT FROM AUTHOR]

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]