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Abstract The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p

Niels Jansen,1 Peter M ten Klooster,2 Harald E Vonkeman,3 Jan R Buitenweg1 1Biomedical Signals and Systems, University of Twente, Enschede, the Netherlands; 2Psychology, Health & Technology, University of Twente, Enschede, the Netherlands; 3Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Enschede, the NetherlandsCorrespondence: Niels Jansen, Email n.jansen@utwente.nlIntroduction: Generalized pain hypersensitivity is a characteristic feature in many different types of chronic pain. Recently, a 7-item self-reported Generalized Pain Questionnaire (GPQ) was developed to evaluate the presence and severity of generalized pain hypersensitivity in chronic pain patients. Here, we evaluate the test–retest reliability of the GPQ and report on preliminary reference values for various patient groups and healthy subjects.Methods: Eighty-five patients diagnosed with Rheumatoid Arthritis (RA) completed the GPQ twice over a 2-week interval. Relative and absolute indicators of reliability were determined using data of 69 patients (81.2% retest response rate). Using readily available datasets, preliminary reference data were established in two nonclinical populations (NCP1; N = 30 and NCP2; N = 111), and for patients diagnosed with RA (N = 114), gout (N = 97), fibromyalgia (N=98), or neuropathy (N = 25), or participants in a pain rehabilitation program (N = 33).Results: Total GPQ scores had an ICC of 0.78 (95% CI: 0.67 to 0.86). While no systematic or proportional differences were found for the GPQ total score; two (near-)significant systematic differences were observed for the individual questions. The standard error of measurement and minimal detectable change were 2.22 and 6.2, respectively. Mean ± SD scores were found to be 0.8 ± 1.2 (NCP1), 4.0 ± 4.6 (NCP2), 6.4 ± 5.5 (Gout), 6.5 ± 5.1 (RA), 8.1 ± 4.5 (Neuropathy), 13.6 ± 4.0 (Rehabilitation) and 16.0 ± 5.0 (Fibromyalgia).Discussion: This study shows that the GPQ has acceptable reliability to be used as a tool to evaluate the presence and intensity of generalized pain hypersensitivity. The absolute measures of reliability and the preliminary reference values reported here aid in the interpretation of future studies with the GPQ.Keywords: generalized pain hypersensitivity, widespread pain, preliminary reference values, reliability, face validity

ABSTRACTThe use of blood products to resuscitate injured and massively bleeding patients in the prehospital and early in-hospital phase of the resuscitation is increasing. Using group O red blood cells (RBC) and low titer group O whole blood (LTOWB) avoids an immediate hemolytic reaction from recipient’s naturally occurring anti-A and – B, but choosing the RhD type for these products is more nuanced and requires the balancing of product availability and survival benefit against the risk of D-alloimmunization, especially in females of childbearing potential (FCP) due to the possible future occurrence of hemolytic disease of the fetus and newborn (HDFN). Recent models have estimated the risk of fetal/neonatal death from HDFN resulting from D-alloimmunization of an FCP during her trauma resuscitation at between 0-6.5% depending on her age at the time of the transfusion and other societal factors including trauma mortality, her age when she becomes pregnant, frequency of different RHD genotypes in the population, and the probability that the woman will have children with different fathers; this is counterbalanced by an approximately 24% risk of death from hemorrhagic shock. This review will discuss the different models of HDFN outcomes following RhD-positive transfusion as well as the results of recent surveys where the public was asked about their preferences for urgent transfusion in light of the risks of fetal/neonatal adverse events.

* Context.-Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice. Currently there are no formal guidelines to assist pathology laboratories in verification and/or validation of such systems. These recommendations are being proposed for the evaluation of machine learning systems in the clinical practice of pathology. Objective.-To propose recommendations for performance evaluation of in vitro diagnostic tests on patient samples that incorporate machine learning as part of the pre-analytical, analytical, or post-analytical phases of the laboratory workflow. Topics described include considerations for machine learning model evaluation including risk assessment, predeployment requirements, data sourcing and curation, verification and validation, change control management, human-computer interaction, practitioner training, and competency evaluation. Data Sources.-An expert panel performed a review of the literature, Clinical and Laboratory Standards Institute guidance, and laboratory and government regulatory frameworks. Conclusions.-Review of the literature and existing documents enabled the development of proposed recommendations. This white paper pertains to performance evaluation of machine learning systems intended to be implemented for clinical patient testing. Further studies with real-world clinical data are encouraged to support these proposed recommendations. Performance evaluation of machine learning models is critical to verification and/or validation of in vitro diagnostic tests using machine learning intended for clinical practice. (Arch Pathol Lab Med. 2024;148:e335-e361; doi: 10.5858/arpa.2023-0042-CP), Institution of machine learning (ML) in the pathology clinical domain has gained momentum and is rapidly advancing. As ML-based clinical decision support (CDS) systems continue to mature, laboratories will increasingly [...]

* Context.--Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools. Objective.--To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation. Data Sources.--Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development. Conclusions.--Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established. doi: 10.5858/arpa.2020-0541-CP, Artificial intelligence (AI) is a focus of intense scientific, business, and governmental interest: global AI scientific publications have increased more than 6-fold in the past 20 years to more than [...]

Background: Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD‐positive, which might cause D‐alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD‐negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). Methods: The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. Results: The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD‐positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. Conclusion: In this model, RhD‐positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events. [ABSTRACT FROM AUTHOR]

Objectives To determine the impact of residual platelets on dilute Russell's viper venom time (DRVVT) assay in frozen-thawed plasma submitted for lupus anticoagulant (LAC) testing. Methods We measured platelet counts in frozen-thawed samples submitted for LAC testing and evaluated the association between platelet count and the DRVVT screening time and ratios. We also spiked platelets into a LAC-positive sample to observe the effect on the DRVVT. Results Progressive increase in platelet count resulted in a statistically significant shortening of the DRVVT assay results on plasma after 1 freeze-thaw cycle. A similar effect was noted on the LAC-positive sample. Conclusions Residual platelets in plasma samples result in shortening of DRVVT assay after 1 freeze-thaw cycle. This may result in a false-negative LAC test result. [ABSTRACT FROM AUTHOR]

The use of blood products to resuscitate injured and massively bleeding patients in the prehospital and early in-hospital phase of the resuscitation is increasing. Using group O red blood cells (RBC) and low titer group O whole blood (LTOWB) avoids an immediate hemolytic reaction from recipient's naturally occurring anti-A and – B, but choosing the RhD type for these products is more nuanced and requires the balancing of product availability and survival benefit against the risk of D-alloimmunization, especially in females of childbearing potential (FCP) due to the possible future occurrence of hemolytic disease of the fetus and newborn (HDFN). Recent models have estimated the risk of fetal/neonatal death from HDFN resulting from D-alloimmunization of an FCP during her trauma resuscitation at between 0-6.5% depending on her age at the time of the transfusion and other societal factors including trauma mortality, her age when she becomes pregnant, frequency of different RHD genotypes in the population, and the probability that the woman will have children with different fathers; this is counterbalanced by an approximately 24% risk of death from hemorrhagic shock. This review will discuss the different models of HDFN outcomes following RhD-positive transfusion as well as the results of recent surveys where the public was asked about their preferences for urgent transfusion in light of the risks of fetal/neonatal adverse events. [ABSTRACT FROM AUTHOR]