Comment in Arch Pathol Lab Med. 2021 Sep 1;145(9):1049-1050.

CONTEXT.—: Pathologists may encounter extraneous pieces of tissue (tissue floaters) on glass slides because of specimen cross-contamination. Troubleshooting this problem, including performing molecular tests for tissue identification if available, is time consuming and often does not satisfactorily resolve the problem. OBJECTIVE.—: To demonstrate the feasibility of using an image search tool to resolve the tissue floater conundrum. DESIGN.—: A glass slide was produced containing 2 separate hematoxylin and eosin (H&E)-stained tissue floaters. This fabricated slide was digitized along with the 2 slides containing the original tumors used to create these floaters. These slides were then embedded into a dataset of 2325 whole slide images comprising a wide variety of H&E stained diagnostic entities. Digital slides were broken up into patches and the patch features converted into barcodes for indexing and easy retrieval. A deep learning-based image search tool was employed to extract features from patches via barcodes, hence enabling image matching to each tissue floater. RESULTS.—: There was a very high likelihood of finding a correct tumor match for the queried tissue floater when searching the digital database. Search results repeatedly yielded a correct match within the top 3 retrieved images. The retrieval accuracy improved when greater proportions of the floater were selected. The time to run a search was completed within several milliseconds. CONCLUSIONS.—: Using an image search tool offers pathologists an additional method to rapidly resolve the tissue floater conundrum, especially for those laboratories that have transitioned to going fully digital for primary diagnosis.

CONTEXT.—: Point-of-care test (POCT) instruments produce lab results with rapid turnaround times. Based on that fact, emergency department (ED) POCT requests are predicated on the belief that rapid test turnaround times lead to improved care, typically a decreased ED length of stay (LOS). OBJECTIVE.—: To compile the available peer-reviewed data regarding use of POCT in the ED with an emphasis on ED-LOS. DATA SOURCES.—: An English-language PubMed search using the following free text terms: ("EMERGENCY" AND "POINT OF CARE") NOT ULTRASOUND as well as "RAPID INFECTIOUS DISEASE TESTING." In addition, the PubMed "similar articles" functionality was used to identify related articles that were not identified on the initial search. CONCLUSIONS.—: Seventy-four references were identified that studied POCT ED use to determine if they resulted in significant changes in ED processes, especially ED-LOS. They were divided into 3 groups: viral-influenza (n = 24), viral-respiratory not otherwise specified (n = 8), and nonviral (n = 42). The nonviral group was further divided into the following groups: chemistry, cardiac, bacterial/strep, C-reactive protein, D-dimer, drugs of abuse, lactate, and pregnancy. Across all groups there was a trend toward a significantly decreased ED-LOS; however, a number of studies showed no change, and a third group was not assessed for ED-LOS. For POCT to improve ED-LOS it has to be integrated into existing ED processes such that a rapid test result will allow the patient to have a shorter LOS, whether it is to discharge or admission.

CONTEXT.—: Delayed recognition of acute kidney injury (AKI) results in poor outcomes in military and civilian burn-trauma care. Poor predictive ability of urine output (UOP) and creatinine contribute to the delayed recognition of AKI. OBJECTIVE.—: To determine the impact of point-of-care (POC) AKI biomarker enhanced by machine learning (ML) algorithms in burn-injured and trauma patients. DESIGN.—: We conducted a 2-phased study to develop and validate a novel POC device for measuring neutrophil gelatinase-associated lipocalin (NGAL) and creatinine from blood samples. In phase I, 40 remnant plasma samples were used to evaluate the analytic performance of the POC device. Next, phase II enrolled 125 adults with either burns that were 20% or greater of total body surface area or nonburn trauma with suspicion of AKI for clinical validation. We applied an automated ML approach to develop models predicting AKI, using a combination of NGAL, creatinine, and/or UOP as features. RESULTS.—: Point-of-care NGAL (mean [SD] bias: 9.8 [38.5] ng/mL, P = .10) and creatinine results (mean [SD] bias: 0.28 [0.30] mg/dL, P = .18) were comparable to the reference method. NGAL was an independent predictor of AKI (odds ratio, 1.6; 95% CI, 0.08-5.20; P = .01). The optimal ML model achieved an accuracy, sensitivity, and specificity of 96%, 92.3%, and 97.7%, respectively, with NGAL, creatinine, and UOP as features. Area under the receiver operator curve was 0.96. CONCLUSIONS.—: Point-of-care NGAL testing is feasible and produces results comparable to reference methods. Machine learning enhanced the predictive performance of AKI biomarkers including NGAL and was superior to the current techniques.

CONTEXT.—: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. OBJECTIVE.—: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. DESIGN.—: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.—: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS.—: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

CONTEXT.—: Three key guiding principles of rural and remote clinical services are to improve health access, improve outcomes, and reduce inequity. In New Zealand, as in other countries, point-of-care testing and technologies can assist in clinical decision-making for acute and chronic conditions and can help to achieve these key health principles for people living in rural and remote locations. This report is a companion article to the other point-of-care testing topics in this special section in this journal. OBJECTIVE.—: To provide readers with insights into where and how point-of-care testing devices and tests can be implemented to improve outcomes in New Zealand settings without on-site pathology laboratory support. The settings in which point-of-care testing devices are used, and the success stories associated with these initiatives, include general practices, pharmacies, workplaces, rural hospitals, and sexual health clinics. DATA SOURCES.—: The information is extracted from published literature and also first-hand experience in remote and rural New Zealand settings. This report also outlines the regulatory and accreditation challenges relating to point-of-care testing devices in New Zealand and includes advice on the selection of devices, training, and ongoing quality assurance for this type of medical testing in remote locations. CONCLUSIONS.—: Point-of-care testing in rural remote settings without laboratory support can be challenging and rewarding for clinicians. It is now, and will be in the future, an even more important component of the health system to improve outcomes and reduce inequity.

CONTEXT.—: Coronavirus infectious disease-19 (COVID-19) diagnostics require understanding of how predictive values depend on sensitivity, specificity, and especially, low prevalence. Clear expectations, high sensitivity and specificity, and manufacturer disclosure will facilitate excellence of tests. OBJECTIVES.—: To derive mathematical equations for designing and interpreting COVID-19 tests, assess US Food and Drug Administration (FDA) Emergency Use Authorization and Health Canada minimum requirements, establish sensitivity and specificity tiers, and enhance clinical performance in low prevalence settings. DESIGN.—: PubMed and other sources generated articles on COVID-19 testing and prevalence. EndNote X9.1 consolidated references. Mathematica and open access software helped prove equations, perform recursive calculations, graph multivariate relationships, and visualize patterns, including a new relationship, predictive value geometric mean-squared. RESULTS.—: Derived equations were used to illustrate shortcomings of COVID-19 diagnostics in low prevalence. Visual logistics helped establish sensitivity/specificity tiers. FDA/Canada's 90% sensitivity, 95% specificity minimum requirements generate excessive false positives at low prevalence. False positives exceed true positives at prevalence lower than 5.3%, or if sensitivity is improved to 100% and specificity to 98%, at prevalence lower than 2%. Recursive testing improves predictive value. Three tiers emerged from these results. With 100% sensitivity, physicians can select desired predictive values, then input local prevalence, to determine suitable specificity. CONCLUSIONS.—: Understanding low prevalence impact will help health care providers meet COVID-19 needs for effective testing. Laypersons should receive clinical performance disclosure when submitting specimens. Home testing needs to meet the same high standards as other tests. In the long run, it will be more cost-effective to improve COVID-19 point-of-care tests rather than repeat testing multiple times.

Comment in Arch Pathol Lab Med. 2021 Apr 1;145(4):391a-391. Arch Pathol Lab Med. 2021 Apr 1;145(4):391b-391.

CONTEXT.—: Minimal residual disease (MRD) testing by flow cytometry is ubiquitous in hematolymphoid neoplasm monitoring, especially B-lymphoblastic leukemia (B-ALL), for which it provides predictive information and guides management. Major heterogeneity was identified in 2014. Subsequently, new Flow Cytometry Checklist items required documentation of the sensitivity determination method and required lower level of detection (LLOD) inclusion in final reports. This study assesses Laboratory Accreditation Program (LAP) participation and new checklist items' impact on flow cytometry MRD testing. OBJECTIVES.—: To survey flow cytometry laboratories about MRD testing for B-ALL and plasma cell myeloma. In particular, enumerate the laboratories performing MRD testing, the proportion performing assays with very low LLODs, and implementation of new checklist items. DESIGN.—: Supplemental questions were distributed in the 2017-A mailing to 548 flow cytometry laboratories subscribed to the College of American Pathologists FL3 Proficiency Testing Survey (Flow Cytometry-Immunophenotypic Characterization of Leukemia/Lymphoma). RESULTS.—: The percentage of laboratories performing MRD studies has significantly decreased since 2014. Wide ranges of LLOD and collection event numbers were reported for B-ALL and plasma cell myeloma. Most laboratories determine LLOD by using dilutional studies and include it in final reports; a higher proportion of LAP participants used these practices than nonparticipants. CONCLUSIONS.—: Several MRD testing aspects vary among laboratories receiving FL3 Proficiency Testing materials. After the survey in 2014, new checklist items were implemented. As compared to 2014, fewer laboratories are performing MRD studies. While LLOD remains heterogeneous, a high proportion of LAP subscribers follow the new checklist requirements and, overall, target LLOD recommendations from disease-specific working groups are met.

CONTEXT.—: Laparoscopic sleeve gastrectomy (LSG) has quickly become the bariatric surgical procedure of choice for patients with obesity who have failed medical management. Laparoscopic sleeve gastrectomy results in a gastric remnant that is routinely subject to pathologic examination. OBJECTIVE.—: To perform a histologic and cost-benefit analysis of gastric remnants post-LSG. DESIGN.—: All LSG cases performed at University Health Network, Toronto, Ontario, Canada, between 2010 and 2019 were reviewed. Specimens that underwent routine histopathologic assessment and ancillary immunohistochemical analysis were analyzed. Baseline patient characteristics and surgical outcomes were obtained from our internal database. The total cost of specimen gross preparation, examination, sampling, and producing and reporting a hematoxylin-eosin slide was calculated. RESULTS.—: A total of 572 patients underwent LSG during the study period and had their specimens examined histologically. A mean of 4.87 blocks generating 4 hematoxylin-eosin slides was produced. The most common histologic findings reported in LSG specimens ranged from no pathologic abnormalities identified together with proton pump inhibitor-related change. A minority of cases demonstrated clinically actionable histologic findings, of which Helicobacter pylori infection was the most common. The total cost for the complete pathologic analysis of these cases amounted to CaD $66 383.10 (US $47 080.21) with a mean of CaD $116.05 (US $82.40) per case. A total of CaD $62 622.75 (US $44 413.30) was spent on full examination of cases that had no further postoperative clinical impact. CONCLUSIONS.—: There is a broad spectrum of pathologic findings in LSG specimens, ranging from clinically nonactionable to more clinically actionable. The vast majority of histologic findings had no clinical impact, with only a minority of cases being clinically significant. This study therefore recommends that LSG specimens be subject to gross pathologic examination in the vast majority of cases. However, sections should be submitted for microscopic analysis if grossly evident lesions are present and if there is a clinical/known history of clinically actionable findings.

CONTEXT.—: Distinguishing the different types of amyloid is clinically important because treatments and outcomes are different. Mass spectrometry is the new gold standard for amyloid typing, but it is costly and not widely available. Therefore, immunolabeling remains the first step in identifying the most common types of amyloidosis. In amyloid subtyping, direct immunofluorescence works well when applied to frozen sections, but immunohistochemistry on formalin-fixed, paraffin-embedded material often yields poor results, particularly for light chain amyloidosis. Recently, paraffin immunofluorescence has been described as a valuable salvage technique in renal pathology when frozen sections are not available but it has not been evaluated for extra-renal diseases. OBJECTIVES.—: To evaluate the use of paraffin immunofluorescence for light-chain detection in extra-renal amyloidosis and other light-chain-associated diseases. DESIGN.—: First, we compared the staining intensity of both light chains between paraffin immunofluorescence and immunohistochemistry on a retrospective cohort of 28 cases of amyloidosis that have been previously typed. Then, we studied the role of paraffin immunofluorescence as an addition to our classical immunohistochemistry panel for amyloidosis typing. RESULTS.—: In the retrospective cohort, we found that paraffin immunofluorescence outperformed immunohistochemistry for light-chain detection. Then, in the prospective part of the study, we showed that the proportion of correctly classified cases increased from 50% to 71.9% with the adjunction of second-intention paraffin immunofluorescence to the immunohistochemistry procedure. CONCLUSIONS.—: We therefore view paraffin immunofluorescence as a significant addition to the routine workflow for detection of light-chain-related diseases.