Ronald Jackups

Measurement of donor-specific HLA antibodies following plasma exchange therapy predicts clinical outcome in pediatric heart and lung transplant recipients with antibody-mediated rejection.

Therapeutic plasma exchange (TPE) is an increasingly utilized immunosuppressive adjunct for treatment of antibody‐mediated rejection (AMR) following organ transplantation. TPE works through removal of donor‐specific HLA antibodies (DSAs) in the recipients plasma. However, there is no clear laboratory measure evaluating efficacy of removal of DSAs or predicting clinical outcome. We hypothesized that semi‐quantitative DSA measurement by multiplex HLA antibody immunoassay may provide qualitative and quantitative data for DSA clearance and predict treatment efficacy. To evaluate this, we retrospectively investigated DSA concentrations and clinical outcome for 21 pediatric patients who received 31 cycles of TPE peri‐operatively as an adjunct treatment for transplantation in the setting of a positive cytotoxic crossmatch (CXM) and in recipients with AMR following heart or lung transplantation. Immunoassay measurement of DSAs during 15/20 cycles correlated significantly with clinical outcome in the AMR treatment group (P = 0.02), demonstrating the utility of DSA measurement in predicting clinical outcome. In contrast, immunoassay correlated with clinical outcome in only 7/11 patients treated peri‐operatively with TPE for CXM‐positive transplantations (P = 0.58). Changes in mean fluorescence intensity (MFI) for the DSAs correlated better with clinical response than surrogate CXM titers in a subset of patients. We conclude that semi‐quantitative measurement of DSAs by immunoassay can predict clinical response to TPE for treatment of AMR is more reliable than surrogate CXM titer, and should be used to guide TPE treatment of AMR. J. Clin. Apheresis 28:301–308, 2013.

Criteria for Reducing Unnecessary Testing for Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Enterovirus in Cerebrospinal Fluid Samples from Adults

ABSTRACT Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n = 10,917). During this study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period.

RBC Distribution Width: Biomarker for Red Cell Dysfunction and Critical Illness Outcome?

Objectives: RBC distribution width is reported to be an independent predictor of outcome in adults with a variety of conditions. We sought to determine if RBC distribution width is associated with morbidity or mortality in critically ill children. Design: Retrospective observational study. Setting: Tertiary PICU. Patients: All admissions to St. Louis Children’s Hospital PICU between January 1, 2005, and December 31, 2012. Interventions: We collected demographics, laboratory values, hospitalization characteristics, and outcomes. We calculated the relative change in RBC distribution width from admission RBC distribution width to the highest RBC distribution width during the first 7 days of hospitalization. Our primary outcome was ICU mortality or use of extracorporeal membrane oxygenation as a composite. Secondary outcomes were ICU- and ventilator-free days. Measurements and Main Results: We identified 3,913 eligible subjects with an estimated mortality (by Pediatric Index of Mortality 2) of 2.94% ± 9.25% and an actual ICU mortality of 2.91%. For the study cohort, admission RBC distribution width was 14.12% ± 1.89% and relative change in RBC distribution width was 2.63% ± 6.23%. On univariate analysis, both admission RBC distribution width and relative change in RBC distribution width correlated with mortality or the use of extracorporeal membrane oxygenation (odds ratio, 1.19 [95% CI, 1.12–1.27] and odds ratio, 1.06 [95% CI, 1.04–1.08], respectively; p < 0.001). After adjusting for confounding variables, including severity of illness, both admission RBC distribution width (odds ratio, 1.13; 95% CI, 1.03–1.24) and relative change in RBC distribution width (odds ratio, 1.04; 95% CI, 1.01–1.07) remained independently associated with ICU mortality or the use of extracorporeal membrane oxygenation. Admission RBC distribution width and relative change in RBC distribution width both weakly correlated with fewer ICU- (r2 = 0.038) and ventilator-free days (r2 = 0.05) (p < 0.001). Conclusions: Independent of illness severity in critically ill children, admission RBC distribution width is associated with ICU mortality and morbidity. These data suggest that RBC distribution width may be a biomarker for RBC injury that is of sufficient magnitude to influence critical illness outcome, possibly via oxygen delivery impairment.

Deep Learning Makes Its Way to the Clinical Laboratory

Are pathologists obsolete? Although the current answer is most certainly no, this question will be asked with increasing intensity as technological advances in clinical diagnostics, such as machine learning and artificial intelligence, prove to be as effective or even more accurate than the judgments of human experts. One area of pathology experiencing rapid expansion in the diagnostic power of computer technology is automated digital image analysis (DIA)2 (1). A recent study has suggested that automated scoring of biomarkers in breast cancer (Ki67, ER, PR, and HER2) by DIA can predict a molecular subtype of cancer with higher sensitivity and specificity than manual scoring by board-certified pathologists (2). The prospect of using such a tool is not restricted to research, as analyzers have been approved by the Food and Drug Administration (FDA) to score these biomarkers (3, 4). Clinical pathology has also become a fertile ground for DIA in the form of an FDA-approved analyzer for peripheral blood smear review (5). This analyzer identifies, classifies, and quantifies leukocytes by morphologic type using a machine learning approach to assist the technologist or pathologist performing manual differential counts. However, there currently is no similar tool for the morphologic characterization of erythrocytes (RBCs) that has been approved by the FDA. In this issue of Clinical Chemistry , Durant et al. present a novel DIA tool that uses very deep convolutional neural networks (CNNs) to predict the morphology of individual RBCs for the identification of significant abnormal populations that may aid in the diagnosis of hematologic and nonhematologic disease …

Prevalence and Seasonal Distribution of Norovirus Detection in Stools Submitted From Pediatric Patients for Enteric Pathogen Testing

The prevalence and seasonal distribution of norovirus infection in children is not well defined. In this study, stool specimens from children suspected of having gastroenteritis were evaluated for the presence of norovirus. When tested retrospectively, 17.4% of samples were positive, primarily with Genogroup GII, peaking in fall and winter.

Impact of order set design on urine culturing practices at an academic medical centre emergency department

Background Urinalysis and urine culture are commonly ordered tests in the emergency department (ED). We evaluated the impact of removal of order sets from the ‘frequently ordered test’ in the computerised physician order entry system (CPOE) on urine testing practices. Methods We conducted a before (1 September to 20 October 2015) and after (21 October to 30 November 2015) study of ED patients. The intervention consisted of retaining ‘urinalysis with reflex to microscopy’ as the only urine test in a highly accessible list of frequently ordered tests in the CPOE system. All other urine tests required use of additional order screens via additional mouse clicks. The frequency of urine testing before and after the intervention was compared, adjusting for temporal trends. Results During the study period, 6499 (28.2%) of 22 948 ED patients had ≥1 urine test ordered. Urine testing rates for all ED patients decreased in the post intervention period for urinalysis (291.5 pre intervention vs 278.4 per 1000 ED visits post intervention, P=0.03), urine microscopy (196.5vs179.5, P=0.001) and urine culture (54.3vs29.7, P<0.001). When adjusted for temporal trends, the daily culture rate per 1000 ED visits decreased by 46.6% (−46.6%, 95% CI −66.2% to –15.6%), but urinalysis (0.4%, 95% CI −30.1 to 44.4%), microscopy (−6.5%, 95% CI −36.0% to 36.6%) and catheterised urine culture rates (17.9%, 95% CI −16.9 to 67.4) were unchanged. Conclusions A simple intervention of retaining only ‘urinalysis with reflex to microscopy’ and removing all other urine tests from the ‘frequently ordered’ window of the ED electronic order set decreased urine cultures ordered by 46.6% after accounting for temporal trends. Given the injudicious use of antimicrobial therapy for asymptomatic bacteriuria, findings from our study suggest that proper design of electronic order sets plays a vital role in reducing excessive ordering of urine cultures.

The Promise—and Pitfalls—of Computerized Provider Alerts for Laboratory Test Ordering

“asasasasassasasasasasdasdasdfasdfasdfasdfasdfasdfasdffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff” The above expletive was typed as “justification” to override an alert message recently implemented in a computerized provider order entry (CPOE)2 system designed to reduce unnecessary repeat laboratory testing. Similar permutations of the home keys “asdf” were also observed. These responses provide clear evidence that the alert was not always welcomed by providers, but they do not clarify whether the failure was due to provider intransigence or poor alert design. In this issue of Clinical Chemistry , Moyer et al. describe the implementation and findings of a CPOE alert designed to reduce unnecessary repeat ordering of 3 tests—ionized calcium (iCa), serum magnesium (Mg), and N-terminal pro-brain natriuretic peptide (NT-proBNP)—in 5 intensive care units at a single institution (1). Unlike the above example, their alert demonstrated considerable success, with decreases in test volumes of 28%–48% in the 90 days following the introduction of the alert. It provides a model for large clinical systems to effectively introduce evidence-based decision-making tools into laboratory ordering practices. It is no secret that laboratory tests are overordered in the clinical environment; a recent metaanalysis demonstrated that tests are overused by 20.6% on average (2). The ordering of unnecessary tests on such a massive scale may impact not only direct healthcare costs, but also patient safety, and may lead to unnecessary follow-up investigation and iatrogenic blood loss due to excess phlebotomy (3). Unfortunately, in large hospitals with high patient volumes, it would be impractical for laboratory directors to evaluate every test individually for appropriateness, and even more difficult to convince providers to change ordering practices. Meeting other evidence-based quality objectives in laboratory ordering is similarly labor-intensive. One increasingly popular method …

Comparison of two platelet transfusion strategies to minimize ABO-nonidentical transfusion, outdating, and shortages using a computer-simulated "virtual blood bank".

Transfusion of ABO‐incompatible platelets (PLTs) is associated with reduced PLT recovery and a risk of transfusion reactions. However, a policy of transfusing only ABO‐identical PLTs may increase wastage due to product outdating. A prospective study attempting to compare the effects of different ABO compatibility strategies could be costly and disruptive to a blood banks operations.

Vascular access for red blood cell exchange: Vascular Access for RBC Exchange

Red blood cell exchange is the process of removing red blood cells from a patient and replacing them with donated blood using either automated or manual techniques. Red blood cell exchange is a well‐recognized and effective therapy for many red blood cell‐related diseases, especially sickle cell disease. However, decisions regarding the best methods for vascular access are not intuitive and must account for the patients clinical condition, complication risks, and lifestyle, especially in the context of long‐term vascular access. In this review, we discuss the recognized indications for red blood cell exchange, considerations for the selection of exchange modality and vascular access, and recommendations for the appropriate care and prevention of risks associated with vascular access.

Abnormalities of platelet aggregation associated with giant granules in a subset of platelets

![Figure][1] A 3-year-old boy presented with a medical history of facial malformation, single kidney, hypoplastic left ventricle, and complex deletion of chromosome 11 at q24.2q25, consistent with Jacobsen syndrome. He had an International Society on Thrombosis and Haemostasis bleeding