Basic Metabolic Panel Research Articles

B-123 Prediction of Opioid Use Duration in Post-Surgical Orthopedic Patients Using CYP2D6 Inhibitor Index and Routine Laboratory Markers

Abstract Background Hydrocodone, the most commonly prescribed opioid in the U.S., is typically used for pain management following surgery and is a known potential drug of abuse with non-negligible risk of addiction. Significant variability in patients’ response to hydrocodone therapy have been reported, owing to both iatrogenic and endogenous sources. The objective of this study is to evaluate the feasibility of predicting post-discharge hydrocodone use in patients who have undergone orthopedic surgery using patient demographics, genotyping, concurrently prescribed medications, and routinely collected laboratory test results. Methods Targeted genotyping was performed on each patient with genes known to affect hydrocodone pharmacokinetics or pharmacodynamics, including CYP2D6, CYP3A4, CYP3A5, CYP2B6, COMT, OPRM1, and ABCB1. An inhibition index for CYP2D6 was calculated by ranking concurrently prescribed medications as weak, moderate, or strong inhibitors of enzyme activity. Pain index, average hydrocodone dose per day during hospital stay, and CYP2D6 estimated activity scores based on allele functionality were included as predictors. In addition, a retrospective chart review of electronic hospital records was performed where basic metabolic panel and complete blood count results were screened within 10 days of each patient's surgery date. Two types of classification and decision tree algorithms were tuned and validated as prediction models using 5-fold cross validation, including a ‘Fast and Frugal Decision Tree’ (FFTree) and an extreme gradient boosting machine (xgBoost). Clinical predictive features were ranked according to the Shapley Additive Explanations (SHAP) values using the xgBoost model. Results Out of 79 total patients with hydrocodone use duration information, 25 were categorized as “Short” and 54 categorized as “Long” using a 1-week threshold. FFTree model selected the top three features of CYP2D6 inhibition index, blood sodium level, and blood creatinine level and obtained a sensitivity and specificity of 0.80 and 0.76, respectively. The xgBoost model, using the same three features, achieved a sensitivity and specificity of 0.872 and 0.628, respectively, an AUROC of 0.814, PRAUC of 0.912, net benefit of 0.359, and was well-calibrated with a Brier score of 0.161. Consistent with previously published results, the predictive capacity of all genotypes analyzed were unremarkable and consistently ranked as the least important features by the xgBoost model SHAP values, due to their low predictive value. Conclusions Both the FFTree and xgBoost models were able to adequately classify the patients according to a 1-week stratification criteria with good to excellent classification performance. Patients with larger CYP2D6 inhibition index were more likely to be classified as “Long” duration. Sodium and creatinine level, which may reflect hydration status and renal function, and therefore hydromorphone elimination rate, were key predictors of post-discharge hydrocodone use duration when combined with the CYP2D6 inhibition index. Further refinement of the proposed models and validation of model robustness and stability using external cohorts is necessary. These results may have implications for providers when prescribing hydrocodone for pain management, where the ability to risk-stratify patients according to their predicted probability of developing opioid use disorder is of clinical importance.

A-368 Feasibility of a Five-Minute Sample-to-Answer Basic Metabolic Panel for Point-of-Care Testing on the Fluxergy Analyzer

Abstract Background Adoption of point-of-care (POC) platforms has been limited by their high cost and limited menu (e.g., molecular only). Fluxergy has developed a cost-effective multimodal POC platform capable of performing the most common clinical chemistry, immunochemistry, hematology, molecular tests in CLIA-waived settings. This method comparison study describes the performance of the Fluxergy’s feasibility stage basic metabolic panel (BMP) with contrived samples compared to the Siemen’s epoc® Blood Analysis System. Methods Fluxergy Analyzer: The Fluxergy Analyzer is a rapid and cost-effective multimodality platform that can perform lab-quality PCR, clinical chemistry, immunochemistry, and cytometry in a single instrument and if required, in a single cartridge. Fluxergy BMP: Fluxergy BMP rapidly quantifies key electrolytes (K+, Na+, Ca2+, Cl-) and metabolites (glucose, creatinine, and BUN) from whole blood in under five minutes on the Fluxergy Analyzer, utilizing the Fluxergy test cards with screen-printed electrochemical sensor. Feasibility Study: A method comparison study was conducted to assess the performance of the feasibility stage Fluxergy BMP using contrived samples generated by spiking known concentrations of K+, Na+, Ca2+, Cl-, and glucose into buffer solutions. Samples were tested in triplicate with both the Fluxergy BMP and Siemen’s epoc® Blood Analysis System at three different concentrations across the reportable range of the epoc® Blood Analysis System. Results The feasibility stage Fluxergy BMP demonstrated strong correlation across the reportable range for K+, Na+, Ca2+, Cl-, and glucose versus the epoc® Blood Analysis System (Table 1). The error percentage for all samples tested except one glucose sample (9.5 mM) was less than 10%. The coefficient of variance for all samples tested except one Ca2+ sample (0.44 mM) was less than ten percent. Conclusions This feasibility data demonstrates the Fluxergy Analyzer is well-suited to perform rapid and accurate metabolic testing from whole blood samples at the POC.

B-130 Time-of-day dependence of running averages for some components of metabolic panels at our hospital: relation to strategy for patient-based quality control

Abstract Background Our hospital system recently reorganized its lab services so as to restrict in-house testing almost exclusively to inpatient testing. This disruption in patient mix caused us to reassess properties of running averages for our most common analytes, for potential use of such data in real-time patient-based quality control (PBQC). In particular, we examined whether there were analytes for which there was significant dependence of running averages on 24-h clock time (time-of-day, TOD). Methods We performed a retrospective analysis of 3-months' data (FY24, Q2) for patient results of 13 components of the Basic Metabolic Panel (BMP) and Comprehensive Metabolic Panel: Albumin*, Alkaline phosphatase, Alanine amino transferase, Aspartate aminotransferase*, Calcium*, Chloride*, CO2*, Creatinine, Potassium*, Total Protein*, Sodium, Total Bilirubin, and Urea. Running averages for 20 consecutive results (20-mers) were computed for data restricted to results within reference intervals. This produced an overall mean (X) and standard-deviation (SD) of 20-mers for each analyte. We then computed the average 20-mer result (Y) reported within 1-h bins across 24-hour clock time (t). Y(t) was regarded as having TOD-dependence if: (a) there was an 8-h interval of contiguous results for Y that were strictly either below or above X; and (b) either nadir or apex values for |Y-X| exceeded 0.5 SD. Results Seven analytes (*, above) demonstrated TOD-dependence of running means for 20-mers according to criteria given above. An example of TOD-dependent Y(t) is shown in Figure (Albumin). Conclusions For our hospital, TOD-dependence of running means was identified for 7 of 13 metabolic panel analytes. TOD-dependence of running means is a circumstance in which use of only a fixed target for running means in PBQC would lead to inherent TOD-dependent variation in capability for systematic error detection. Use of TOD-dependent targets for PBQC would be appropriate in these cases.

A-208 Price Transparency of Laboratory Tests Across all Licensed Hospitals in Tennessee

Abstract Background The Hospital Price Transparency Final Rule federally mandates hospitals to provide gross price, discounted cash, payer-specific negotiated charges, and de-identified minimum and maximum negotiated rates within a machine-readable file and user-friendly display of shoppable services. Since implementation, compliance has been low and price variability has continued. Methods To assess hospital compliance, barriers to pricing information, and price variability in Tennessee, all hospitals websites were queried for gross, cash, and Blue Cross Blue Shield (BCBS) prices for 8 high-frequency laboratory tests in both mandated pricing sources. Barriers including click counts, data availability, and intra-hospital price discrepancies were noted. Results Only 2.8% of the 145 hospitals were compliant with federal law. Sub-analyses of the available machine-readable files, price estimators, and shoppable services files, only 50.4%, 4.9%, and 21.4% were found to be compliant, respectively. Barriers to pricing information included requiring protected health information (55.9%), missing at least 1 pricing source (7.6%), having no pricing sources available (6.2%), and involving more than 3 clicks to access cash price in machine-readable files (54.1%) and price estimators (68.6%.) The median total number of clicks from homepage to cash price in the machine-readable file and price estimator was 4 (range: 1-7) and 10.5 (range: 6-15), respectively. Average intra-hospital discrepancy for Basic Metabolic Panel cash prices across pricing sources was $101.30 (range: $0-1012.40). Price variability across Tennessee is shown in Figure 1. Maximum to minimum price multiples ranged from 29 to 114 for gross price, 57 to 243 for cash price, and 25 to 115 for BCBS price indicating price variability. Gross and cash prices were affected by median household income of the hospital’s county. Conclusions Our study shows low compliance with price transparency mandates, inequitable pricing affected by median household income, inconsistent and inaccessible pricing, and continued price variability in Tennessee.

P22-05 Associations between blood mercury levels and basic metabolic panel in freshwater fish (Ctenopharyngodon idella)

P22-05 Associations between blood mercury levels and basic metabolic panel in freshwater fish (Ctenopharyngodon idella)

Discordant High Activated Partial Thromboplastin Time Relative to Anti-Xa Values in Hospitalized Patients is an Independent Risk Factor for Increased 30-day Mortality.

The activated partial thromboplastin time (aPTT) and anti-factor-Xa levels (anti-Xa) are both used to monitor patients on unfractionated heparin. Our previous study demonstrated that patients with discordant high aPTT relative to anti-Xa had higher rates of mortality and bleeding events. To determine if underlying patient characteristics drive both discordance and adverse outcomes or if discordance is an independent risk factor to adverse outcomes. We analyzed all patients hospitalized at the Stanford Hospital between January 2011 and December 2019 who had simultaneous aPTT and anti-Xa levels performed. From the electronic medical record, we extracted and analyzed 51 patient features including baseline coagulation laboratory results, demographics, values of other common laboratories (basic metabolic panel, complete blood count, etc.), diagnostic procedures, medications, and death. A total of 17,728 patients had 78,701 paired aPTT and anti-Xa levels. Patients with discordant aPTT and anti-Xa where aPTT (seconds) was elevated beyond the expected therapeutic range had a higher 30-day mortality (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.78-2.63, p < 0.001). Sectioning the patients based on the degree of discordance and whether aPTT or anti-Xa were signaling excess anticoagulation, we found those with an elevated aPTT discordant to their anti-Xa level had the highest odds of death (OR: 2.46, 95% CI: 1.99-3.10) compared with the concordant group. This finding was still present after controlling for patient comorbidity and other laboratory results at hospital admission. After controlling for patient features strongly associated with increased mortality in heparinized patients, we identified that the discordant pattern of high aPTT to anti-Xa served as an independent predictor of 30-day all-cause mortality, with a higher degree of discordance associated with increased odds of 30-day mortality.

Methods of a cluster-randomized, type II hybrid implementation effectiveness trial to prospectively assess extended-duration thromboprophylaxis for at-risk medical patients being discharged to prevent hospital-associated venous thromboembolism

BackgroundVenous thromboembolism (VTE) is the third leading cause of preventable hospital-associated (HA) death. Most HA-VTE, including fatal pulmonary emboli, occur among medically ill patients. The rate of symptomatic VTE more than doubles over the first 21 days after hospital discharge. Trials have demonstrated that the burden of HA-VTE may be reduced with postdischarge thromboprophylaxis; however, few patients receive this therapy. We formerly validated the ability of eVTE (eVTE is the abbreviation for a risk assessment tool constituted by 2 calculations: one predicts 90-day VTE and the other predicts 30-day major bleeding derived from only elements of the complete blood count and basic metabolic panel and age) to identify medical patients being discharged with both an elevated risk of VTE and a low risk of bleeding. ObjectivesImplement a cluster-randomized, stepped wedge, type II hybrid implementation/effectiveness trial generating an alert among select at-risk patients upon discharge for implementation of thrombosis chemoprophylaxis in a 23-hospital not-for-profit healthcare system. MethodsWe use the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to guide implementation and outcomes reporting. ResultsThe primary outcome for aim 1 (implementation) is the prescription of rivaroxaban 10 mg daily for 30 days as postdischarge thromboprophylaxis among at-risk patients. The primary efficacy and safety outcomes (effectiveness) are the 90-day composite of symptomatic VTE, myocardial infartcion, nonhemorrhagic stroke, all-cause mortality, and 30-day major bleeding. ConclusionThe eVTE trial will provide high-quality, real-world evidence on the effectiveness and safety of a pragmatic intervention to implement targeted postdischarge thromboprophylaxis using decision support embedded in the electronic health record.

Evaluating initial screening practices for calcium dysregulation after acute traumatic spinal cord injury: a retrospective review

ObjectivesThe purpose of this study was to determine the frequency of which calcium homeostasis markers are obtained in the acute setting after an initial traumatic spinal cord injury (TSCI).DesignRetrospective chart review of a limited data set linking ICD 10 codes designating TSCI to corresponding calcium homeostasis markers for patients with an initial chart encounter for TSCI.SettingA level 1 trauma center in Virginia, United StatesMethodsThe statistical software SPSS was used to calculate summary statistics including frequency, mean, and standard deviation for calcium homeostasis markers (basic metabolic panel, magnesium, spot urine calcium, testosterone panel, liver function tests, Vitamin D level, C-telopeptide, parathyroid hormone, celiac panel, DXA imaging report) as well as the mean and standard deviation for time to first check of the marker.ResultsMost markers were not obtained besides calcium. Only 10 of 80 (12.5%) of subjects had a Vitamin D level (mean 28, SD 23) checked during acute admission (mean days to check 1.5, SD 1.6), with most other markers checked much less frequently.ConclusionsMost calcium homeostasis markers were not checked on acute admission after TSCI. Future studies on implementing a standardized calcium homeostasis marker protocol for monitoring and potential medical intervention should be explored.

Decreasing Blood Transfusions in Premature Infants Through Quality Improvement.

Packed red blood cell transfusions (pRBCT) in preterm infants have been associated with significant morbidity. Although infants <26 weeks' gestational age typically require several pRBCT, preterm infants born between 26 and 34 weeks' gestational age may also require pRBCT during their hospitalization that are potentially preventable. We aimed to reduce pRBCT in this population by 20%. This quality improvement project was conducted in the Duke University Hospital NICU between July 2018 and February 2023. Interventions included the implementation of evidence-based transfusion thresholds, supporting bone marrow erythropoiesis, and reducing laboratory specimen volumes by increasing capillary test panels. The rates per 1000 patient days for pRBCT (outcome measure), number of new patients initiated on erythropoietin (process measure), number of basic metabolic panels (process measure), and total capillary panels (process measure) were monitored during the project period. Statistical process control charts were used to observe trends over time. Among infants born between 26 0/7 and 34 6/7 weeks' gestational age, the rate of pRBCT decreased from an average of 23.8 to 12.7 transfusions per 1000 patient days, which is a 46.6% decrease. Increases in the use of erythropoietin and capillary panels were observed, along with a decrease in the use of basic metabolic panels. There was no change in mortality or the rate of necrotizing enterocolitis. Improvement was sustained for 24 months after implementation. pRBCT can be decreased in preterm infants born between 26 and 34 completed weeks' gestation through a combination of strategies utilizing quality improvement methodology.

Selection of Single-Analyte Delta Check Rules with Logistic Regression for Detection of Intravenous Fluid Contamination in a Clinical Chemistry Laboratory.

The conventional single-analyte delta check, utilized for identifying intravenous fluid contamination and other preanalytical errors, is known to flag many specimens reflecting true patient status changes. This study aimed to derive delta check rules that more accurately identify contamination. Results for calcium, creatinine, glucose, sodium, and potassium were retrieved from 326 103 basic or comprehensive metabolic panels tested between February 2021 and January 2022. In total, 7934 specimens showed substantial result changes, of which 1489 were labeled as either contaminated or non-contaminated based on chart review. These labeled specimens were used to derive logistic regression models and to select the most predictive single-analyte delta checks for 4 common contaminants. Their collective performance was evaluated using a test data set from October 2023 comprising 14 717 specimens. The most predictive single-analyte delta checks included a calcium change by ≤-24% for both saline and Plasma-Lyte A contamination, a potassium increase by ≥3.0 mmol/L for potassium contamination, and a glucose increase by ≥400 mg/dL (22.2 mmol/L) for dextrose contamination. In the training data sets, multi-analyte logistic regression models performed better than single-analyte delta checks. In the test data set, logistic regression models and single-analyte delta checks demonstrated collective alert rates of 0.58% (95% CI, 0.46%-0.71%) and 0.60% (95% CI, 0.49%-0.74%), respectively, along with collective positive predictive values of 79% (95% CI, 70%-89%) and 77% (95% CI, 68%-87%). Single-analyte delta checks selected by logistic regression demonstrated a low false alert rate.

Serum sickness-like reaction to D-mannose supplement: a case report

BackgroundSerum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents.Case presentationA 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free.ConclusionsThis case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Tennessee hospital noncompliance with price transparency legislation for 8common laboratory tests.

The goal of this study was to assess hospital compliance with federal price transparency mandates and barriers to pricing information in Tennessee. All hospitals websites were queried for gross, cash, and BlueCross BlueShield of Tennessee prices for 8 high-frequency laboratory tests in 2 Centers for Medicare & Medicaid Services-mandated pricing sources: (1) a machine-readable file of all available services and (2) a consumer-friendly display of 300 shoppable services. Barriers, including click counts, data availability, and intrahospital price discrepancies, were noted. Of the 145 Tennessee hospitals assessed, 97.2% were noncompliant with the Centers for Medicare & Medicaid Services final rule. Subanalysis of available machine-readable files, price estimators, and shoppable services files demonstrated 49.6%, 95.1%, and 78.6% noncompliance, respectively. Barriers to pricing information included requiring protected health information (55.9%), missing at least 1 pricing source (7.6%), having no pricing sources available (6.2%), and involving more than 3 clicks to access the cash price in machine-readable files (54.1%) and price estimators (68.6%.) Average intrahospital discrepancy for basic metabolic panel cash prices across pricing sources was $101.30 (range, $0-1012.40). Our study showed high levels of noncompliance with price transparency laws, inconsistent and inaccessible pricing, and continued challenges facing patients in Tennessee.

Diagnostic utility of capnography in emergency department triage for screening acidemia: a pilot study

BackgroundCapnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia.ResultsWe performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO2) and venous partial pressure of CO2, admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\left[HC{O}_{3}^{-}\\right]\\le 22 \ ext{mEq/L}$$\\end{document} or \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ pH< 7.35$$\\end{document}) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51–0.75, p = 0.03). A low end-tidal CO2 (EtCO2 < 32 mmHg) had positive (LR+) and negative (LR−) likelihood ratios of 4.68 (95% CI 2.59–8.45) and 0.34 (95% CI 0.19–0.61) for acidemia, respectively—corresponding to sensitivity 71.4% (95% CI 51.3–86.8) and specificity 84.7% (95% CI 74.3–92.1). The c-statistic for EtCO2 was 0.849 (95% CI 0.76–0.94, p = 0.00). Waveform analysis further revealed characteristically abnormal capnograms that were associated with underlying pathophysiology.ConclusionsCapnography is a quantitative method of screening acidemia in patients and can be implemented feasibly in Emergency Department triage as an adjunct to vital signs. While it was shown to have only modest ability to predict acidemia, triage capnography has wide generalizability to screen other life-threatening disease processes such as sepsis or can serve as an early indicator of clinical deterioration.

Abstract 3392: Generation and characterization of transgenic oncopig model for lung cancer

Abstract Lung cancer (LC) is the leading cause of cancer-associated death in the United States. Preclinical findings in small animal models do not translate into human clinics. There is an urgent need to develop relevant preclinical large animal models for LC. We describe a novel method to induce LC in transgenic pigs carrying Cre-inducible KrasG12D and TrP53R167H mutations (Oncopigs). The Oncopigs (n=12; 9 females, and 3 males) at 9 weeks of age were anesthetized and adenovirus (1 × 1011 PFU) carrying Cre recombinase gene (Ad-Cre) ± polybrene (1:100) ± IL-8 (5 ng/ml) was injected via flexible bronchoscopy with two techniques: (1) Bronchial lavage (n=6) and (2) Transbronchial needle injection (n=6) into different lung lobes. As controls, a combination of polybrene ± IL-8 was injected without AdCre into the contralateral lobes in the same pigs (n=8). Oncopigs were monitored via clinical monitoring, blood counts, basic metabolic panel, and contrast-enhanced computed tomography (CT) imaging for LC progression and metastasis at 3-, 4-, 7-, 10-, 16-, and 26 weeks post-intervention. All animals tolerated the injections with expected weight gains. Blood counts and metabolic panels remained normal during LC progression. At the site of injection/lavage, lung masses were detected on CT imaging at 3 weeks post-injections. However, a decrease in masses was observed on CT at 7 weeks post-intervention. The decrease in size of the lung masses coincided with increasing attenuation. No distant metastases were observed on CT imaging. Lavage-based lesions appeared to be more heterogeneous with surrounding inflammatory changes. Transbronchial-injection-based lesions appeared more consolidated and coin-shaped without surrounding inflammatory changes. Control injection sites did not show any mass growth on CT imaging. Immunohistochemistry analysis on lung tumors revealed increased pancytokeratin, trichrome, E-cad, Ki-67, IBA, and CD3 expression. Further, immunofluorescence revealed decreased E-Cad, CK-19, and Zo-1 expression, whereas increased expression of N-Cad, FN1, snail, CD44, α-SMA, and γ-catenin, was observed in the LC and metastatic tissue compared to normal. We successfully generated and characterized a novel transgenic Oncopig LC model. There is robust tumor production status post AdCre delivery. One of four Oncopigs had carcinomatous metastatic skin growth. The remaining 7 Oncopigs are monitored longitudinally for tumor growth and development of metastasis. Citation Format: Kirtan Joshi, Nagabhishek Sirpu, Amanda Schmelzle, Ravikanth Poonooru, Benjamin Nelson, Pradeep Subramanyam, Colleen Garrett, Mariana Sponchiado, Sarah Schlink, Samantha Gerb, Jesse Porter, Dae Kim, Jeffrey Kunin, Jeffrey Bryan, Timothy Hoffman, Bhanu Telugu, Jussuf Kaifi, Satyanarayana Rachagani. Generation and characterization of transgenic oncopig model for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3392.

Importance of Serum Albumin in Deep Learning-Based Prediction of Cognitive Function Data in the Aged Using a Basic Blood Test.

Recently, a method using deep learning has been developed to estimate the risk of developing dementia. This method uses general blood test data from routine health examinations that reveal lifestyle-related diseases, which can lead to vascular cognitive impairment via arteriosclerosis, as well as systemic metabolic disorders that are unrelated to lifestyle, such as nutritional disorders. In this study, we investigated the differences in the accuracy of estimating the risk of dementia based on the presence or the absence of blood test parameters reflecting nutritional disorders while focusing on the association between malnutrition and the risk of dementia in frail, elderly individuals. The objective of this study was to evaluate the impact of including or excluding serum albumin, which reflects nutritional status, on the accuracy of predicting cognitive function in older adults using blood test data. We estimated cognitive function, as measured by the Mini-Mental State Examination (MMSE), using the deep learning model (DLM). The estimation was performed based on general blood test data, including complete blood tests and basic metabolic panels, obtained from a selection of 1287 patients admitted to Osaka Medical and Pharmaceutical University Hospital. The data were divided into two groups: individuals aged 65 and above and those aged below 65. The impact of including or excluding serum albumin on the predictive performance of MMSE was examined within each group. In those aged below 65, the mean squared error (MSE) of the DLM was 5.33 without albumin and 4.62 with albumin, showing a -0.71 improvement with albumin. In those aged 65 and above, the MSE of the DLM was 6.38 without albumin and 6.28 with albumin, showing a -0.1 improvement with albumin. The present study demonstrated that including serum albumin in the input data resulted in lower estimation errors for MMSE across all applied algorithms in the group aged 65 and above. This is consistent with previously reported studies that have shown the adverse effects of malnutrition on cognitive function in older adults. This study highlighted the significance of serum albumin, which reflects nutritional status, as an important assessment variable for estimating MMSE from blood test data, particularly in individuals aged 65 and above.

Impact and frequency of IV fluid contamination on basic metabolic panel results using quality metrics

Abstract Objectives Clinical laboratories invest substantial time and resources to mitigate measurement error but potential errors during the preanalytical phase of testing are not subjected to the same level of scrutiny. Herein, we assess the proportions of intravenous (IV) fluid contamination sufficient to exceed common performance metrics and compare it to contaminated results flagged by current protocols. Methods Basic metabolic panels performed between 01/2017 and 07/2022 were extracted from the laboratory information system (n=928,742). Contamination was simulated for common IV fluid types. The thresholds at which contaminated results exceeded total allowable error (TEa), reference change values (RCV), or changed normality/critical flags were calculated. The mixture ratio of IV fluid contamination detected by technologists during routine analysis was estimated. Results The TEa and RCV was exceeded at a mixture ratio ≤0.10 for chloride, glucose, calcium, and potassium for both normal saline (NS) and 5 % dextrose in water (D5W). At a simulated mixture ratio of 0.10, 51.39 % of calcium and 21.17 % of potassium results would be expected to be incorrectly reported with an abnormal/critical flag with NS contamination and 99.74 % of sodium and 100 % of glucose results to be incorrectly flagged with D5W. Retrospective results flagged as contaminated revealed a median mixture ratio of 0.18 and 0.24 for D5 and non-D5 fluids. Conclusions At a mixture ratio of at least 0.10, IV fluid contamination causes relevant error between patients’ true concentrations and those reported. However, current procedures cannot reliably detect 10 % contamination.

Automating the Detection of IV Fluid Contamination Using Unsupervised Machine Learning.

Intravenous (IV) fluid contamination is a common cause of preanalytical error that can delay or misguide treatment decisions, leading to patient harm. Current approaches for detecting contamination rely on delta checks, which require a prior result, or manual technologist intervention, which is inefficient and vulnerable to human error. Supervised machine learning may provide a means to detect contamination, but its implementation is hindered by its reliance on expert-labeled training data. An automated approach that is accurate, reproducible, and practical is needed. A total of 25 747 291 basic metabolic panel (BMP) results from 312 721 patients were obtained from the laboratory information system (LIS). A Uniform Manifold Approximation and Projection (UMAP) model was trained and tested using a combination of real patient data and simulated IV fluid contamination. To provide an objective metric for classification, an "enrichment score" was derived and its performance assessed. Our current workflow was compared to UMAP predictions using expert chart review. UMAP embeddings from real patient results demonstrated outliers suspicious for IV fluid contamination when compared with the simulated contamination's embeddings. At a flag rate of 3 per 1000 results, the positive predictive value (PPV) was adjudicated to be 0.78 from 100 consecutive positive predictions. Of these, 58 were previously undetected by our current clinical workflows, with 49 BMPs displaying a total of 56 critical results. Accurate and automatable detection of IV fluid contamination in BMP results is achievable without curating expertly labeled training data.

Utility of Vizient Clinical Data Base as a benchmarking tool for laboratory stewardship programs

Abstract Establishing an effective laboratory stewardship program across healthcare systems to improve patient care has been of growing interest. Despite general guidelines from various organizations, clear definitions for these laboratory-based quality measures, and associated benchmarks, are still lacking. Hence, we utilized Vizient® Clinical Data Base (CDB) as a tool to benchmark our institution against U.S. News and World Reports’ Honor Roll (USNW) healthcare organizations 2021-2022. We focused on inpatient laboratory testing with specific targets including mean laboratory resource units used per patient per day to obtain an overview of our institution’s overall performance, daily basic metabolic panel and CBC test ordering patterns across various service lines, and C-reactive protein (CRP) to erythrocyte sedimentation rate (ESR) order ratios compared to USNW hospitals. As one of the five institutions with the highest mean laboratory resource units used per case per day (12.7) from January 1, 2021-January 31, 2022, we investigated this further to identify tests driving this result. Of all the laboratory tests ordered, blood gas was identified at the 99th percentile compared to peers. Stratifying by service, we found cardiac surgery (17%), general medicine (15%), pulmonary/critical care (11%), neonatology (10%) and transplant (9%) services at our institution were the major contributors to blood gas orders. Investigating daily laboratory test orders (BMP, CBC) showed that our institution was at the 46th and 71st percentile overall, respectively. Further CBC analysis showed that general medicine (28%) and oncology (11%) services were the major contributors for the test volume and highest total resource units used per quarter in 2021. Assessing CRP to ESR ratio depicted that our institution’s ratio of 2.2 was lower compared to USNW hospitals’ average of 2.9, meaning ESR is likely overutilized. In conclusion, Vizient CDB can be used as a resource for benchmarking laboratory utilization patterns. It can be helpful in developing road maps and prioritizing interventions for lab stewardship programs. This study identified a general overuse of laboratory resources at the hospital compared to peers, and identified some intervention targets including blood gas testing and ESR.

Hemophagocytic Lymphohistiocytosis As an Immune-Related Adverse Events in a Patient with Advanced Lung Adenocarcinoma

I ntroduction: Immune checkpoint inhibitors (ICIs) have been approved as single agents or in combination with cytotoxic chemotherapy for use in the treatment of different tumor types including skin, lung, kidney, endometrium, bladder..., especially in advanced stages. ICIs are usually well tolerated and despite their demonstrated clinical benefit, severe immune-related adverse events (irAEs) can sometimes occur, including colitis, hepatitis, myocarditis, glomerulonephritis, pneumonitis, hypophysitis... Here we are reporting a case of hemophagocytic lymphohistiocytosis (HLH), a rare but potentially life-threatening complication of ICI therapy. Case presentation: We present the case of a 60-year-old female with metastatic adenocarcinoma of left lung who presented to the emergency room with a week history of generalized weakness, worsening dyspnea on exertion and decreased appetite while on maintenance ICI with pembrolizumab for approximately 1 year. On admission vital signs were a blood pressure of 88/70mmhg, pulse rate of 139 beats per minute, respiratory rate of 20 cycles per minute, temperature of 98.3°F and oxygen saturation of 98% on room air. Physical exam was unremarkable. A complete blood count revealed leukopenia of 2.7k/uL, hemoglobin of 11.8 g/dL, and mild thrombocytopenia of 131k/uL. A basic metabolic panel was significant for hyponatremia of 133 mmol/L, blood urea nitrogen of 43mg/dL, and creatinine of 1.71mg/dL. She was started on empiric broad-spectrum antibiotics with IV vancomycin and cefepime due to concern for infection in the setting of recurrent febrile episodes and neutropenia. Worsening pancytopenia prompted further work-up and showed elevated ferritin of 19581, lactate dehydrogenase of 2380, folate &amp;gt; 20, vitamin B 12 of 1645, iron level of 62, elevated total and direct bilirubin of 6.3 and 2.9 mg/dL, haptoglobin &amp;lt; 10 mg/dL, fibrinogen level of 174, C- reactive protein of 73.9. Elevated soluble IL2- receptor elevated at 10336.7, d-dimer &amp;gt; 20, elevated partial thromboplastin time of 51.1, Prothrombin Time of 20.5, INR of 1.7. Peripheral blood smear was unremarkable. Hemophagocytic lymphohistiocytosis was suspected and a bone marrow was performed prior to initiation of intravenous steroids. Bone marrow showed evidence of abundant histiocytes with hemophagocytosis of nucleated cells. She was discharged on an oral steroid taper. She has since been well without evidence of tumor progression off therapy for over 2 years now. Discussion: HLH is a rare but potentially life-threatening complication of ICI therapy that requires prompt recognition and management. Our patient responded well to steroids and did not require cytotoxic chemotherapy with etoposide.

THU387 Euglycemic Diabetic Ketoacidosis And SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. N. Terrigno: None. Background: Diabetic ketoacidosis (DKA) is a known adverse effect of SGLT-2 inhibitors. (1) Incidences of euglycemic diabetic ketoacidosis in patients on SGLT-2 inhibitors are reported on less. Clinical Case: A 39-year-old male past medical history of uncontrolled, non-insulin dependent diabetes mellitus and pancreatitis who presented with abdominal pain, nausea and coffee ground emesis. On initial work up, basic metabolic panel showed blood glucose level of 175 mg/dL with an elevated anion gap of 22 mmol/L. Initial differentials included suspicion for euglycemic diabetic ketoacidosis or acute intraabdominal pathology. Venous blood gas showed metabolic acidosis, with a pH of 7.21 and bicarbonate of 9.7 mmol/L, beta hydroxybutyrate was elevated at 7.83 mmol/L. CT abdomen pelvis found a small hiatal hernia, gastric wall thickening, likely gastritis, and was negative for other intraabdominal pathology. Home medications of the patient included dapagliflozin, semaglutide, metformin, gabapentin, and pantoprazole. Patient was admitted with the diagnosis of suspected euglycemic diabetic ketoacidosis and was started on an insulin drip along with D5 0.45 normal saline. Patient’s anion gap was monitored with basic metabolic panel orders every two hours. The insulin drip was discontinued once the patient had two consecutive normal anion gaps and the patient was subsequently started on a subcutaneous insulin regimen. Conclusion: SGLT-2 inhibitors may cause euglycemic diabetic ketoacidosis based on the physiology of the SGLT-2 transporter and the pharmacology of the SGLT-2 inhibitors. (2) Clinical importance of this case report is to consider euglycemic diabetic ketoacidosis in patients on SGLT-2 inhibitors presenting with nausea, vomiting with normal blood glucose to not delay in the diagnosis and treatment of this life-threatening condition.