Citations

Abstract Introduction Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct lymphoid neoplasm. However, differentiation from diffuse large B-cell lymphoma (DLBCL) can be difficult due to the need for close clinicopathologic correlation and variability in morphology and immunophenotype. In addition, a recent study identified lymphomas that share molecular and morphological features with PMBCL, yet do not involve the mediastinum. Correct classification of PMBCL may impact therapeutic decision making, increasing the demand for more accurate diagnostic methods. Recent research identified a new gene expression signature that robustly differentiated PMLBCL from DLBCL in both training and independent validation cohorts using RNA isolated from routinely available formalin-fixed, paraffin-embedded (FFPE) tissues. Methods This assay, known as the “Lymph3Cx,” utilizes the nCounter platform (NanoString Technologies, Seattle, WA) and consists of probes for 58 target genes (including both discriminatory and housekeeping genes) that can distinguish PMLBCL cases from DLBCL as well as the “cell-of-origin” subtypes of DLBCL. In the current study reported here, the Molecular Diagnostics–Arizona Laboratory (MDAZL) performed a full validation of the Lymph3Cx assay for use in our clinical diagnostic laboratory. Results Assay performance included accuracy (92.9%), precision (100%), analytical sensitivity (100 ng RNA limit of detection), analytical specificity (measures are in place to prevent interfering substances), reproducibility between technologists and technical replicates (100%), specimen stability (18 months for unstained tissue sections), and RNA Isolation Kit Utility (two kits with equal performance) in order to become the first CLIA-certified, CAP-accredited clinical diagnostics laboratory to offer a molecular assay for distinction of PMLBCL from DLBCL. Conclusion The Lymph3Cx assay will be prospectively used for evaluation of Mayo Clinic patients and for use as an integrated biomarker in clinical trials.

Abstract Introduction Measurement of hemoglobin A1c (HbA1C) is used for the diagnosis and management of patients with diabetes. Methods for measuring HbA1C are classified on the basis of charge differences (cation exchange chromatography) or structural differences (boronate affinity chromatography). Some cation exchange high-performance liquid chromatography (HPLC) analyzers may be prone to interferences from hemoglobin variants. Historically, our lab used two methods to report HbA1C results: cation exchange HPLC (VariantII) with reflex to boronate affinity HPLC (Ultra2) methods. A new analyzer (BioRad D-100) with improved interference detection and thresholds for interference was evaluated. The objectives of this study were (1) assess the comparability of HbA1c results between D-100, VariantII, and Ultra2; (2) evaluate the need for maintaining a reflex method; and (3) calculate cancellation rates before and after implementing D-100. Methods HbA1c was measured by cation exchange methods using VariantII Turbolink, D-100 (BioRad), and boronate affinity using Ultra2Affinity (Trinity Biotech) according to the manufacturer’s recommendations with the following analytical measuring ranges (AMRs), 4.0% to 17.6%, 4.0% to 18.0%, and 4.0% to 17.6%, respectively. D-100 was compared to VariantII (n = 26) and Ultra2 (n = 31) using residual patient samples from provider-ordered HbA1c having no chromatography flags and with the following chromatography flags on VariantII (n = 113): variant window (n = 41), HbA1c <4.0% (n = 24), HbA1a + HbA1b >5% (n = 19), HbF >5% (n = 9), P3 >10% (n = 6), HbA1c >17.6% (n = 4), unknown peak (n = 3), labile 5% to 15% (n = 3), labile >15% (n = 3), and HbS >60% (n = 1). The cancelation rates were calculated at baseline (January 1-31, 2018) and postimplementation of D-100 (September 20, 2018, to January 22, 2019). Results HbA1c results from D-100 were within ±0.3 or 5% with the following frequencies: Ultra2 in 96.2% (25/26) with VariantII in 96.8% (30/31) using samples with no chromatography flags. A total of 113 samples with abnormal VariantII flags were tested using D-100 with 82% (n = 92) not exceeding interference limits for result reporting. These D-100 results were within ±0.3 or 5% of Ultra2 results with the following frequencies: 38.5% (10/26) of samples below (n = 23) or above (n = 3) the AMR, 85.3% (29/34) of results with Hb variant flags, 68.0% (17/25) with unknown/minor peaks, and 71.4% (5/7) with HbF <15%. The clinical concordance was also assessed according to the following decision limits: normal <5.6%, prediabetic = 5.7% to 6.4%, and diabetic >6.5%. Results were concordant in 88% with variant peaks (12/13 w/HbA1c <5.6%, 8/11 w/HbA1c = 5.7%-6.4%, 10/10 w/HbA1c >6.5%), 84% with minor peaks (5/6 w/HbA1c <5.6%, 0/2 w/HbA1c = 5.7%-6.4%, 16/17 w/HbA1c >6.5%), and 86% with HbF (3/3 w/HbA1c <5.6%, 2/3 w/HbA1c = 5.7%-6.4%, 1/1 w/HbA1c >6.5%). Results above/below AMR had 100% concordance (>16.0% or <4.4%). The frequency of VariantII rule violation was 2.1% in January 2018, with 53 of 117 having results confirmed as <4.0% or >16.0% by Ultra2, 2 of 117 reported by Ultra2, and 62 being cancelled due to HbF >15% (n = 23) or variant Hb >60% (n = 39). The frequency of rule violation using only D-100 since implementation was 2.2%. Conclusion Implementation of D-100 has removed the need for boronate affinity reflex testing and maintained similar cancellation rates.

Abstract Introduction Lymph2Cx lymphoma cell-of-origin assay (LM2CX) was developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) to better categorize diffuse large B-cell lymphoma (DLBCL). NanoString has licensed the assay and is currently pursuing FDA approval. In the meantime, the test is offered exclusively as a lab-developed test (LDT) by the Mayo Clinic Molecular Diagnostics–Arizona Lab (MDAZL) to Mayo Clinic Enterprise patients. In order to comply with these restrictions, the normal workflow for Mayo Clinic Rochester has been modified as cases are sent to Arizona. Rochester consultants order LM2CX using their local laboratory information system (LIS). Slides are prepared by Rochester histology and then shipped to Arizona, where they are entered into the Arizona LIS and processed. In July 2018, we discovered numerous cases that were ordered but not shipped. Because this step took place at the LIS transition between Arizona and Rochester, it was not detected immediately. Methods Allied Health Staff (AHS) colleagues in Rochester and Arizona had the unique opportunity to collaborate. After Arizona AHS identified the problem, they reached out to the Rochester pathology reporting specialists (PRSs) and began a joint improvement project. Together, we were able to measure the impact of the problem, with Arizona auditing digitally, while Rochester audited physical cases. We found 29% of the cases were handled improperly over a 6-month time period. In order to eliminate the gap, Rochester implemented several improvements, including training, tagging all LM2CX cases, and huddle discussions, while Arizona AHS monitored the process digitally. Results Since implementation of improvements, we have had zero defects. Modifications to AHS/consultant training in Rochester will ensure continued success. Conclusions This intervention illustrates the importance of strong collaborations in order to quickly respond to testing issues and provide the greatest value to patients.

Background Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky. Methods A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR. Results Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48–0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001). Conclusions Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.

AbstractBackgroundBreast reconstruction (BR) is the reconstructive surgical technique that focuses on restoring normal form and function to the breast following oncologic resection. The goal of this study was to determine if BR disparities exist among rural female patients in Kentucky.MethodsA retrospective (2006‐2015), population‐based cohort study was conducted on breast cancer patients (stages I‐III) treated with mastectomy with or without BR. We used 2013 Beale codes to stratify patients according to geographic status. Chi‐square tests were used to examine the association of BR along the rural‐urban continuum. A multivariate logistic regression model controlling for patient, disease, and treatment factors was used to predict BR. The likelihood of BR was reported in odds ratios (OR) using a 95% confidence interval (CI).ResultsOverall, 10,032 patients met study criteria. Of those, 2,159 (21.5%) underwent BR. The rate of BR among urban, near‐metro, and rural patients was 31.1%, 20.4%, and 13.4%, respectively (P < .001). Multivariate analysis revealed that women from near metro (OR 0.54, CI: 0.47‐0.61; P < .001) and rural areas (OR 0.36, CI: 0.31‐0.41; P < .001) were less likely to undergo BR than women from urban areas.ConclusionAlthough BR benefits are well documented, women from rural Kentucky undergo BR at lower rates and are less likely to receive BR than their urban counterparts. Efforts should seek to promote equitable access to BR for all patients, including those from rural areas.

Roberts Bartholow, a physician, born and raised in Maryland, was a surgeon and Professor in Medicine who had previously served the Union during the Civil War. His interest in scientific research drove him to perform the first experiment that tested the excitability of the human brain cortex. His historical experiment on one of his patients, Mary Rafferty, with a cancerous ulcer on the skull, was one of his great accomplishments. His inference from this experiment and proposed scientific theory of cortical excitation and localization in humans was one of the most critically acclaimed topics in the medical community, which attracted the highest commendation for the unique discovery as well as criticism for possible ethical violations. Despite that criticism, his theory and methods of cortical localization are the cornerstone of modern brain mapping and have, in turn, led to countless medical innovations.