Anatomic pathology quality assurance: Developing an LIS based tracking and documentation module for intradepartmental consultations.

Background: An electronic intradepartmental consultation system for anatomic pathology (AP) was conceived and developed in the laboratory information system (LIS) in 2019. Previously, all surgical pathology intradepartmental consultative activities were initiated and documented with paper forms which circulated with the pertinent microscopic slides and were eventually filed. In this study, we discuss the implementation and utilization of an electronic intradepartmental AP consultation system. Methods: Workflows and procedures were developed to organize intradepartmental surgical pathology consultations from the beginning to the end point of the consultative activities entirely using a paperless system that resided in the LIS. Results: The electronic consult system allowed electronic documentation of all steps of intradepartmental consultative activities. The system provided tracking ability for consulted cases and improved access to consult discussion for all departmental personnel, staff, and trainees. Consultation work queue was created for each pathologist and a summary of individual consultative workload was possible. Documentation of anatomic pathology quality assurance for intradepartmental consultative activity was easily assessed. Conclusions: The electronic intradepartmental consult system has allowed our department to electronically track intradepartmental consult cases, store the consultative opinion text with the case, record the pathologists involved, and document the consultation for internal quality assurance review as well as for accrediting organizations. Summarization of pathologist workload related to consultative activity was quantifiable and optimization of the consultative process was maximized for education in an academic setting.

The Neuropathology of 1p36 Deletion Syndrome: An Autopsy Case Series.

1p36 deletion syndrome is the most common terminal deletion syndrome, manifesting clinically as abnormal facies and developmental delay with frequent cardiac, skeletal, urogenital, and renal abnormalities. Limited autopsy case reports describe the neuropathology of 1p36 deletion syndrome. The most extensive single case report described a spectrum of abnormalities, mostly related to abnormal neuronal migration. We report the largest published series of 1p36 autopsy cases, with an emphasis on neuropathologic findings. Our series consists of 3 patients: 2 infants (5-hours old and 23-days old) and 1 older child (11 years). Our patients showed abnormal cortical gyration together with a spectrum of neuronal migration abnormalities, including heterotopias and hippocampal abnormalities, as well as cerebellar hypoplasia. Our findings thus support the role of neuronal migration defects in the pathogenesis of cognitive defects in 1p36 deletion syndrome and broaden the reported neuropathologic spectrum of this common syndrome.

Nationwide practices in the use of central venous catheters for therapeutic plasma exchange in the inpatient setting.

INTRODUCTION: Therapeutic plasma exchange (TPE) is often impacted by difficulties in obtaining an adequate and safe vascular access. This study evaluated the rates, predictive factors, and clinical outcomes associated with central venous catheter (CVC) use during the inpatient TPE procedures. METHODS: The Nationwide Readmissions Database, 2016 to 2017 was used to identify hospitalizations with TPE with and without CVC insertion. RESULTS: During the study period, there were 35 429 hospitalizations with TPE (pediatric 6.1%, mean ± standard deviation (SD) age 50.9 ± 20.0 years, female 52.7%). CVC insertion was documented in 24 414 (73.4%) adult and 1596 (73.5%) pediatric hospitalizations. In pediatric patients, age >15 years, higher disease severity, and private insurance were associated with higher odds of CVC insertion. In adults, female sex, obesity, concurrent hemodialysis, and higher disease severity were associated with CVC insertion. Adults with private insurance and both adult and pediatric hospitalizations at the teaching hospitals had lower odds of CVC placement. All patients with CVC insertion had longer length of hospital stay, and adults with CVC insertion also had higher hospital charges, higher in-hospital mortality, and lower likelihood of being discharged to home. CONCLUSION: CVC insertion is performed for the majority of inpatient TPE procedures and CVC use appears to correlate with worse clinical outcomes.

Teaching Pathology in an Integrated Preclinical Medical School Curriculum and Adaptations to COVID-19 Restrictions.

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on education at all age levels, including professional schools and health professions programs. We describe the experience of adapting preclinical medical school courses within an integrated curriculum to virtual instruction. A major feature of two of the courses were pathology small groups adapted from pathology courses in the previous medical school curriculum. These small groups were designed to use facilitated groups of 8 to 10 students. With a sudden change to virtual learning, these small groups were shifted to large group virtual sessions. In general, the conversion went well, with ongoing optimization of the format of the large group sessions mainly occurring over the first several sessions. End-of-course student evaluations were generally positive, but with a preference toward returning to live sessions in the future. Scores on 5 multiple choice examinations in the spring 2020 course were essentially identical in mean, standard deviation, and distribution to examinations in the previous 2 years of the course that had similar layout and topic organization. We discuss the challenges and successes of the switch to virtual instruction and of teaching pathology content within an integrated medical school curriculum.

Frozen Section Quality Assurance.

OBJECTIVES: Composite frozen section turnaround time has limited value, precluding assessment of certain processes: slide preparation (technical) and diagnosis (interpretation). We examined whether measuring these elements could identify delays, hypothesizing that longer times were related to (1) inefficient technical processes and (2) case-specific diagnostic challenges. METHODS: Technical and interpretive times were determined for 1,992 specimens submitted for frozen section in 2017; the data were sorted by surgical specialty. Mean and quartile times were determined for each category with all specimens assessed equally, including those with multiple frozen section blocks. RESULTS: Technical times were significantly longer than interpretive times. Specialty grouping facilitated trend identification and enabled assessment of technical and interpretation challenges. We identified technical issues with certain gross specimens involving overdissection and interpretation delays for specific neoplasms and margins. CONCLUSIONS: Measuring technical and interpretative times and subcategorizing by specialty has aided the assessment of frozen section processing in our laboratory, enabling case isolation for process improvement.

Congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (cc-TGA, also known as L-transposition) is a rare condition that represents approximately 0.5% of congenital heart disease. It is characterized by atrioventricular and ventriculoarterial discordance. Patients with cc-TGA are at risk for cardiac arrhythmias due to abnormalities of the conduction system. We present an autopsy case of a 49-year-old man with cc-TGA who died unexpectedly, likely as a result of a fatal arrhythmia. This case illustrates the cardiac pathology characteristic of cc-TGA and describes how to grossly identify inversion of the atrioventricular valves.

Display Characteristics and Their Impact on Digital Pathology: A Current Review of Pathologists' Future "Microscope".

Digital displays (monitors) are an indispensable component of a pathologists' daily workflow, from writing reports, viewing whole-slide images, or browsing the Internet. Due to a paucity of literature and experience surrounding display use and standardization in pathology, the Food and Drug Administration's (FDA) has currently restricted FDA-cleared whole-slide imaging systems to a specific model of display for each system, which at this time consists of only medical-grade (MG) displays. Further, given that a pathologists' display will essentially become their new surrogate "microscope," it becomes exceedingly important that all pathologists have a basic understanding of fundamental display properties and their functional consequences. This review seeks to: (a) define and summarize the current and emerging display technology, terminology, features, and regulation as they pertain to pathologists and review the current literature on the impact of different display types (e.g. MG vs. consumer off the shelf vs. professional grade) on pathologists' diagnostic performance and (b) discuss the impact of the recent digital pathology device componentization and the coronavirus disease 2019 public emergency on the pixel pathway and display use for remote digital pathology. Display technology has changed dramatically over the past 20 years and continues to change at a rapid rate. There is a paucity of published studies to date that investigate how display type affects pathologist performance, with more research necessary in order to develop standards and minimum specifications for displays in digital pathology. Given the complexity of modern displays, pathologists must become better informed regarding display technology if they wish to have more choice over their future "microscopes."

Artificial Intelligence in Pathology: A Simple and Practical Guide.

Artificial intelligence (AI) is having an increasing impact on the field of pathology, as computation techniques allow computers to perform tasks previously performed by people. Here, we offer a simple and practical guide to AI methods used in pathology, such as digital image analysis, next-generation sequencing, and natural language processing. We not only provide a comprehensive review, but also discuss relevant history and future directions of AI in pathology. We additionally provide a short tabular dictionary of AI terminology which will help practicing pathologists and researchers to understand this field.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

BACKGROUND: Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. METHODS: We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. RESULTS: Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. CONCLUSIONS: Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology.

Implementation of Epic Beaker Anatomic Pathology at an Academic Medical Center.

BACKGROUND: Beaker is a relatively new laboratory information system (LIS) offered by Epic Systems Corporation as part of its suite of health-care software and bundled with its electronic medical record, EpicCare. It is divided into two modules, Beaker anatomic pathology (Beaker AP) and Beaker Clinical Pathology. In this report, we describe our experience implementing Beaker AP version 2014 at an academic medical center with a go-live date of October 2015. METHODS: This report covers preimplementation preparations and challenges beginning in September 2014, issues discovered soon after go-live in October 2015, and some post go-live optimizations using data from meetings, debriefings, and the project closure document. RESULTS: We share specific issues that we encountered during implementation, including difficulties with the proposed frozen section workflow, developing a shared specimen source dictionary, and implementation of the standard Beaker workflow in large institution with trainees. We share specific strategies that we used to overcome these issues for a successful Beaker AP implementation. Several areas of the laboratory-required adaptation of the default Beaker build parameters to meet the needs of the workflow in a busy academic medical center. In a few areas, our laboratory was unable to use the Beaker functionality to support our workflow, and we have continued to use paper or have altered our workflow. In spite of several difficulties that required creative solutions before go-live, the implementation has been successful based on satisfaction surveys completed by pathologists and others who use the software. However, optimization of Beaker workflows has continued to be an ongoing process after go-live to the present time. CONCLUSIONS: The Beaker AP LIS can be successfully implemented at an academic medical center but requires significant forethought, creative adaptation, and continued shared management of the ongoing product by institutional and departmental information technology staff as well as laboratory managers to meet the needs of the laboratory.

Implementation of Epic Beaker Clinical Pathology at an academic medical center.

BACKGROUND: Epic Beaker Clinical Pathology (CP) is a relatively new laboratory information system (LIS) operating within the Epic suite of software applications. To date, there have not been any publications describing implementation of Beaker CP. In this report, we describe our experience in implementing Beaker CP version 2012 at a state academic medical center with a go-live of August 2014 and a subsequent upgrade to Beaker version 2014 in May 2015. The implementation of Beaker CP was concurrent with implementations of Epic modules for revenue cycle, patient scheduling, and patient registration. METHODS: Our analysis covers approximately 3 years of time (2 years preimplementation of Beaker CP and roughly 1 year after) using data summarized from pre- and post-implementation meetings, debriefings, and the closure document for the project. RESULTS: We summarize positive aspects of, and key factors leading to, a successful implementation of Beaker CP. The early inclusion of subject matter experts in the design and validation of Beaker workflows was very helpful. Since Beaker CP does not directly interface with laboratory instrumentation, the clinical laboratories spent extensive preimplementation effort establishing middleware interfaces. Immediate challenges postimplementation included bar code scanning and nursing adaptation to Beaker CP specimen collection. The most substantial changes in laboratory workflow occurred with microbiology orders. This posed a considerable challenge with microbiology orders from the operating rooms and required intensive interventions in the weeks following go-live. In postimplementation surveys, pathology staff, informatics staff, and end-users expressed satisfaction with the new LIS. CONCLUSIONS: Beaker CP can serve as an effective LIS for an academic medical center. Careful planning and preparation aid the transition to this LIS.

Use of a data warehouse at an academic medical center for clinical pathology quality improvement, education, and research.

BACKGROUND: Pathology data contained within the electronic health record (EHR), and laboratory information system (LIS) of hospitals represents a potentially powerful resource to improve clinical care. However, existing reporting tools within commercial EHR and LIS software may not be able to efficiently and rapidly mine data for quality improvement and research applications. MATERIALS AND METHODS: We present experience using a data warehouse produced collaboratively between an academic medical center and a private company. The data warehouse contains data from the EHR, LIS, admission/discharge/transfer system, and billing records and can be accessed using a self-service data access tool known as Starmaker. The Starmaker software allows users to use complex Boolean logic, include and exclude rules, unit conversion and reference scaling, and value aggregation using a straightforward visual interface. More complex queries can be achieved by users with experience with Structured Query Language. Queries can use biomedical ontologies such as Logical Observation Identifiers Names and Codes and Systematized Nomenclature of Medicine. RESULT: We present examples of successful searches using Starmaker, falling mostly in the realm of microbiology and clinical chemistry/toxicology. The searches were ones that were either very difficult or basically infeasible using reporting tools within the EHR and LIS used in the medical center. One of the main strengths of Starmaker searches is rapid results, with typical searches covering 5 years taking only 1-2 min. A "Run Count" feature quickly outputs the number of cases meeting criteria, allowing for refinement of searches before downloading patient-identifiable data. The Starmaker tool is available to pathology residents and fellows, with some using this tool for quality improvement and scholarly projects. CONCLUSION: A data warehouse has significant potential for improving utilization of clinical pathology testing. Software that can access data warehouse using a straightforward visual interface can be incorporated into pathology training programs.

Pilot clinical trial of hedgehog pathway inhibitor GDC-0449 (vismodegib) in combination with gemcitabine in patients with metastatic pancreatic adenocarcinoma.

PURPOSE: The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449-mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma. EXPERIMENTAL DESIGN: Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity. RESULTS: On pretreatment biopsy, 75% of patients had elevated sonic hedgehog (SHH) expression. On posttreatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22, and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre- and postbiopsy. The median progression-free and overall survival for all treated patients were 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values or relative change on posttreatment biopsy), and survival. Grade ≥ 3 adverse events were noted in 56% of patients. CONCLUSION: We show that GDC-0449 for 3 weeks leads to downmodulation of GLI1 and PTCH1, without significant changes in CSCs compared with baseline. GDC-0449 and gemcitabine were not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer.

Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction.

BACKGROUND: Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. METHODS: Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. RESULTS: The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11ß-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement of testosterone in women. Using two-dimensional similarity calculations, all compounds with high cross-reactivity also showed a high degree of similarity to the target molecule of the immunoassay. CONCLUSIONS: Compounds producing cross-reactivity in steroid hormone immunoassays generally have a high degree of structural similarity to the target hormone. Clinically significant interactions can occur with structurally similar drugs (e.g., prednisolone and cortisol immunoassays; methyltestosterone and testosterone immunoassays) or with endogenous compounds such as 21-deoxycortisol that can accumulate to very high concentrations in certain disease conditions. Simple similarity calculations can help triage compounds for future testing of assay cross-reactivity.

Autoverification in a core clinical chemistry laboratory at an academic medical center.

BACKGROUND: Autoverification is a process of using computer-based rules to verify clinical laboratory test results without manual intervention. To date, there is little published data on the use of autoverification over the course of years in a clinical laboratory. We describe the evolution and application of autoverification in an academic medical center clinical chemistry core laboratory. SUBJECTS AND METHODS: At the institution of the study, autoverification developed from rudimentary rules in the laboratory information system (LIS) to extensive and sophisticated rules mostly in middleware software. Rules incorporated decisions based on instrument error flags, interference indices, analytical measurement ranges (AMRs), delta checks, dilution protocols, results suggestive of compromised or contaminated specimens, and 'absurd' (physiologically improbable) values. RESULTS: The autoverification rate for tests performed in the core clinical chemistry laboratory has increased over the course of 13 years from 40% to the current overall rate of 99.5%. A high percentage of critical values now autoverify. The highest rates of autoverification occurred with the most frequently ordered tests such as the basic metabolic panel (sodium, potassium, chloride, carbon dioxide, creatinine, blood urea nitrogen, calcium, glucose; 99.6%), albumin (99.8%), and alanine aminotransferase (99.7%). The lowest rates of autoverification occurred with some therapeutic drug levels (gentamicin, lithium, and methotrexate) and with serum free light chains (kappa/lambda), mostly due to need for offline dilution and manual filing of results. Rules also caught very rare occurrences such as plasma albumin exceeding total protein (usually indicative of an error such as short sample or bubble that evaded detection) and marked discrepancy between total bilirubin and the spectrophotometric icteric index (usually due to interference of the bilirubin assay by immunoglobulin (Ig) M monoclonal gammopathy). CONCLUSIONS: Our results suggest that a high rate of autoverification is possible with modern clinical chemistry analyzers. The ability to autoverify a high percentage of results increases productivity and allows clinical laboratory staff to focus attention on the small number of specimens and results that require manual review and investigation.