Abnormal Laboratory Values Research Articles

Utility of Weekly Laboratory Monitoring in the Expectant Management of Hypertensive Disorders of Pregnancy.

Our retrospective cohort study evaluates the diagnostic yield of weekly laboratory surveillance in outpatient management of hypertensive disorders of pregnancy (HDP) based on patient clinical status at the time of laboratory testing. The study included 459 patients and 1,082 laboratory episodes: 356 (32.9%) episodes were performed in the setting of concerning clinical findings and 726 (67.1%) when the patient was asymptomatic. Overall, the diagnostic yield for abnormal laboratory values (n=11) was 1.0% (95% CI 0.4-1.6%) of all assessments performed and 2.4% (95% CI 1.0-3.8%) among all patients in the cohort. The prevalence of abnormal test results was higher in patients with clinical findings (2.8%, 95% CI 1.1-4.5%) compared with those who were asymptomatic (0.1%, 95% CI 0-0.2%) ( P <.01). Clinical findings suggestive of worsening disease had a 91% sensitivity (95% CI 59-100%) and a 99% (95% CI 99-100%) negative predictive value for abnormal laboratory values. Directed screening based on signs and symptoms, rather than universal weekly screening, may be a potential strategy to lower costs and reduce multiple blood draws for patients with HDP, because there is a low diagnostic yield for this practice.

An Ontology-Based Approach to Improving Medication Appropriateness in Older Patients: Algorithm Development and Validation Study.

Background: Inappropriate medication in older patients with multimorbidity results in a greater risk of adverse drug events. Clinical decision support systems (CDSSs) are intended to improve medication appropriateness. One approach to improving CDSSs is to use ontologies instead of relational databases. Previously, we developed OntoPharma-an ontology-based CDSS for reducing medication prescribing errors. Objective: The primary aim was to model a domain for improving medication appropriateness in older patients (chronic patient domain). The secondary aim was to implement the version of OntoPharma containing the chronic patient domain in a hospital setting. Methods: A 4-step process was proposed. The first step was defining the domain scope. The chronic patient domain focused on improving medication appropriateness in older patients. A group of experts selected the following three use cases: medication regimen complexity, anticholinergic and sedative drug burden, and the presence of triggers for identifying possible adverse events. The second step was domain model representation. The implementation was conducted by medical informatics specialists and clinical pharmacists using Protégé-OWL (Stanford Center for Biomedical Informatics Research). The third step was OntoPharma-driven alert module adaptation. We reused the existing framework based on SPARQL to query ontologies. The fourth step was implementing the version of OntoPharma containing the chronic patient domain in a hospital setting. Alerts generated from July to September 2022 were analyzed. Results: We proposed 6 new classes and 5 new properties, introducing the necessary changes in the ontologies previously created. An alert is shown if the Medication Regimen Complexity Index is ≥40, if the Drug Burden Index is ≥1, or if there is a trigger based on an abnormal laboratory value. A total of 364 alerts were generated for 107 patients; 154 (42.3%) alerts were accepted. Conclusions: We proposed an ontology-based approach to provide support for improving medication appropriateness in older patients with multimorbidity in a scalable, sustainable, and reusable way. The chronic patient domain was built based on our previous research, reusing the existing framework. OntoPharma has been implemented in clinical practice and generates alerts, considering the following use cases: medication regimen complexity, anticholinergic and sedative drug burden, and the presence of triggers for identifying possible adverse events.

Biotin induced biochemical hyperthyroidism: a case report and review of the literature

BackgroundBiotin is a commonly used supplement for hair, nail, and skin. Recent literature suggests that high-dose biotin therapy for neurological diseases like Multiple sclerosis can interfere with lab results that use biotin/streptavidin immunoassay, called biotin interference. Biotin interference can affect thyroid lab results, giving biochemical hyperthyroidism.Case presentationOur patient, a 64-year-old white man with a known history of multiple sclerosis, presented with elevated free T3, free T4, and low TSH that resembled hyperthyroidism. He had no symptoms of hyperthyroidism except some fatigue and tachycardia on the first encounter. He was started on anti-thyroid medications. He was then re-evaluated since his lab results remained the same after two months of anti-thyroid medications. It was found that he was on biotin, 10000mcg/day, for his multiple sclerosis. Biotin was discontinued, and five days later his lab results returned to normal values.ConclusionThe lack of knowledge of biotin use by patients can lead to misdiagnosis of patients’ thyroid lab results and improper management. Awareness about biotin interference and abnormal thyroid lab values should be a priority among clinicians and the public. If the biotin is discontinued on time, such misdiagnosis can be avoided.

OATH trial: A phase II clinical trial evaluating the combination of onapristone with anastrozole for women with hormone receptor positive endometrial cancer—Preliminary results.

5601 Background: Endometrial cancer is the most common gynecologic cancer and is primarily treated with chemotherapy. Many endometrial cancers though express hormone receptors and may respond to hormonal therapy, a potentially attractive non-chemotherapy alternative in such a population of women. The aim of OATH is to investigate the potential of dual hormonal blockade through the combination of antiprogesterone and anti-estrogen therapy via the administration of onapristone extended release (ONA) plus anastrozole (ANA), respectively. OATH is an open-label, multicenter, investigator-initiated, non-randomized, phase 2 study to evaluate the safety and efficacy of ONA + ANA in patients (pts) with endometrial cancer (EC). ClinicalTrials.gov Identifier: NCT04719273. Methods: Pts received ONA 50 mg twice daily plus ANA 1 mg once daily and were treated until progressive disease (PD) or unacceptable toxicity. Co-primary endpoints were 4-month progression-free survival (PFS) rate and overall response rate (ORR). A sample size of 25 pts will achieve 80% power to detect an improvement in 4-month PFS estimates from 25% (historical) to 52% and an improvement in response rate from 15% (historical) to 37%, using two-sided exact test at 5% significance level. Secondary endpoints include PFS, disease control rate (DCR), and safety. Results: As of January 20, 2023, 14 pts were enrolled. Median age was 67 years (44-80). ECOG performance status was 0 (36%), and 1 (64%). Number of prior chemotherapy regimens was 0 (1 pt,7%), 1 (9 pts, 64%) and 2 (4 pts, 29%). Seven (50%) pts received radiotherapy and 3 (21%) pts received prior checkpoint inhibitor therapy. Median treatment duration was 4.2 (1.0-19.9) months, and 8 pts remain on treatment. Adverse events were mainly grade 1 and 2. The most common treatment-related adverse events (AEs) and abnormal laboratory values were hot flashes (36%), alanine transferase (ALT) increased (29%), aspartate aminotransferase (AST) increased (29%), nausea (29%), and diarrhea (21%). No treatment-related serious AE, deaths on treatment, or treatment-related drug discontinuations were reported. The 4-month PFS Kaplan-Meier rate was 63.5%. Among 13 pts who had at least one tumor assessment after baseline, the best overall response was: 1 complete response, 1 partial response (response rate: 15.4%), 9 (69%) stable disease, and 2 (15.4%) progressions. Updated results will be presented. Conclusions: Preliminary results of dual hormonal blockade using ONA and ANA in heavily pretreated pts with EC suggest that this combination ONA + ANA has promising activity and is well tolerated. Clinical trial information: NCT04719273 .

Phase Ib, open-label study of add on therapy with CK0804 in participants with myelofibrosis, with suboptimal response to ruxolitinib.

TPS7087 Background: Drugs targeting JAK2 inhibition including ruxolitinib have led to significant improvement in quality of life and survival of myelofibrosis (MF) patients, however almost 30% have suboptimal response and disease remains incurable. Novel therapies are urgently needed. In addition to mutation-driven stem cell-derived clonal myeloproliferation, recent data support role of reactive cytokine- and chemokine-driven inflammatory fibrosis that contribute to MF pathogenesis, specifically, abnormal CXCR4/CXCL12 axis can drive disease progression and extramedullary hematopoeisis. Targeting bone marrow inflammation is emerging as potential therapeutic strategy for MF. Adoptive therapy with allogeneic, cord blood (CB) derived Regulatory T cells (Tregs) have shown to be safe in bone marrow failure patients. CXCR4 enriched CB Tregs (CK0804) show faster egress across transwell membrane in response to SDF1α and preferential homing to bone marrow, in vivo. We hypothesize that multiple infusions of CK0804 may decrease inflammation and improve clinical outcomes in MF. Methods: Single arm study consisting of safety run-in of 9 participants followed by expansion cohort of additional 15 participants using 3+3+3 study design. MF patients receiving ruxolitinib therapy &gt; 3 months prior to enrollment with stable dose for at least 8 weeks prior to Day 1, unlikely to benefit from further ruxolitinib monotherapy in opinion of investigator would be eligible. Each participant will receive single infusion of CK0804 at fixed dose of 100 million Treg cells administered every 28 days. Participants will continue their ruxolitinib therapy. Participants with no treatment limiting toxicity (TLT) after 28 days or those with toxicity with clear alternative explanation (e.g. disease progression) or transient (≤72 hrs) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination will receive up to six 28-day treatment cycles AND 6 months of follow up after last infusion of CK0804. Primary Objective: Determine safety and tolerability of CK0804 as add-on therapy in MF, with suboptimal response to ruxolitinib. Primary endpoint: Safety, tolerability and TLTs of CK0804 as assessed by incidence and severity of AE and SAEs determined by NCI CTCAE Version 5.0. Secondary Objective: Determine efficacy of CK0804 as add-on therapy in MF, with suboptimal response to ruxolitinib. Secondary endpoint: Assessment of overall response rate and its duration, using modified International Working Group Myeloproliferative Neoplasm Research and Treatment and European Leukemia Net consensus report; Rate of anemia response and Rate of spleen response by imaging at and after 24 weeks; Symptom burden assessed using Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score scale. Safety data from cohort 1 will be presented. Clinical trial information: NCT05423691 .

Rapid Remission of Chronic, Progressive Conditions and Reducing Polypharmacy by Utilizing Lifestyle Therapy to Target Insulinemic Lifestyle Components

This case study provides evidence that homeostatic control in a patient with hyperglycemia and other metabolic abnormalities associated with insulin resistance can be rapidly restored utilizing lifestyle therapy. The patient, an overweight, non-Hispanic White male aged 70 years, had been medicated for hypertension and Type 2 diabetes mellitus for 12 years. From baseline during 21 months of follow-up, HbA1c decreased from 6.6% to 5.4%, mean fasting glucose decreased from 125 mg/dL to 94 mg/dL, blood pressure decreased from 130/85 mmHg to 100/64 mmHg, estimated glomerular filtration rate increased from 50 ml/min/1.73m² to 58 ml/min/1.73m², waist circumference decreased from 118.8 cm to 90.8 cm, and liver function improved with aspartate transaminase decreasing from 44 IU/L to 17 IU/L and alanine transaminase decreasing from 34 IU/L to 21 IU/L. Each of these metabolic corrections was observed while eliminating respective disease-specific medications. These metabolic improvements were achieved using primary recommended lifestyle therapy specifically targeting known insulinemic lifestyle components. This case study shows that the utilization of primary recommended, ongoing lifestyle therapy targeting insulinemic lifestyle components can rapidly improve markers of insulin resistance and normalize abnormal laboratory values while eliminating the risk of polypharmacy and the direct costs of medication.

Enhanced anti-tumor activity of CD5 CAR T cells manufactured with tyrosine kinase inhibitors in patients with relapsed/refractory T-ALL.

7002 Background: An effective CAR T cell platform for the therapy of T-ALL requires minimizing CAR-driven fratricide of normal T cells. CD5 is a pan-T-cell surface protein present in ~85% of T-ALL. We developed a 2nd generation CD5 CAR that produces minimal T cell fratricide without additional engineering. Tonic CAR signaling accelerated terminal differentiation of CD5 CAR T cells potentially reducing their potency. In this study, we evaluated whether blocking tonic signaling with tyrosine kinase inhibitors (TKI) ibrutinib and dasatinib improves anti-leukemic activity of CD5 CAR T cells in patients with r/r T-ALL (NCT03081910). Methods: In the initial cohort of patients (CH1, n = 8), we generated CD5 CAR T cells from autologous PBMCs followed by expansion in the presence of IL-7 and IL-15 without TKI. In the subsequent cohort (CH2, n = 7) we manufactured cells from autologous (Arm A; n = 4) or HSC donor-derived (Arm B; n = 3) PBMCs in the presence of TKI. A total of 14 pts were treated (9 adult and 5 pediatric; age 11-70 years [median 36 yrs]); one pediatric pt was treated on both cohorts. Results: In CH1, all pts received autologous CAR T cells: 1 pt on DL1 (1x107 CAR T cells/m2), 5 on DL2 (5x107 CAR T cells/m2), and 2 on DL3 (1x108 CAR T cells/m2). In CH2, we treated 4 pts on Arm A (one on DL2; 3 on DL3) and 3 pts on Arm B (all on DL1). The overall expansion of CAR T cells was comparable between cohorts, but we observed more sustained persistence of CD5 CAR T cells in pts on CH2. In CH1, one pt experienced a morphologic CR. Of 7 pts treated on CH2, we observed 4 MRD-negative CRs (2 on Arm A and 2 on Arm B). The CAR T cells produced minimal early toxicity with most grade ≥3 AEs related to cytopenias, febrile neutropenia and transient abnormal laboratory values. CRS occurred in 3 pts on CH1 and 4 on CH2 (Arm A: n = 1; Arm B: n = 3); all ≤ grade 2. No pts developed ICANS. Two pts in CH2 (one on Arm A and Arm B) developed EBV viremia and post-transplant/immunodeficient lymphoproliferative disease (LPD) at wks 5 and 7 post-infusion, respectively. Both were treated with intensive multiagent chemotherapy, and one pt also received EBV specific T cells (EBVSTs) with significant reduction in viral load. Unfortunately, both passed away from complications of treatment for PTLD (unrelated to EBVSTs) with no evidence of residual T-ALL. No other significant infections occurred. Conclusions: These results demonstrate CD5 CAR T cells can induce clinical responses in heavily treated patients with r/r T-ALL. Manufacturing CD5 CAR T cells with TKI improved their potency and anti-tumor activity but also possibly suppressed CD5+ virus-specific T-cells thus leading to 2 cases of EBV associated LPD. We have subsequently modified our clinical protocol to administer prophylactic rituximab to EBV seropositive pts and identify a partially matched EBVST line prior to CAR T cell infusion as a strategy to prevent additional cases of LPD in future subjects. Clinical trial information: NCT03081910 .

Single-Center Analysis of Essential Laboratory Testing in Patients with Newly Diagnosed Celiac Disease

To analyze laboratory testing results from pediatric patients newly diagnosed with celiac disease to determine the usefulness of each test derived from recommended guidelines. Serological testing at the time of diagnosis from patients enrolled in our celiac disease registry from January 2018 through December 2021 was reviewed. The incidence of abnormal laboratory results, routinely obtained as per the recommendations of Snyder etal and our institution's Celiac Care Index, was assessed. Rates of abnormal laboratory values and estimated costs associated with these screening measures were analyzed. Our data demonstrated abnormalities in all serological testing obtained at celiac diagnosis. Hemoglobin, alanine aminotransferase, ferritin, iron, and vitamin D screening were found to be abnormal with notable frequency. Only 7% of patients had an abnormal thyroid-stimulating hormone and <0.1% had an abnormal free T4. Nonresponse to hepatitis B vaccination was prominent, with 69% of patients considered nonimmune. Screening protocols as currently outlined in our Celiac Care Index resulted in an estimated cost of approximately $320000 during our study. Review of screening laboratory results at our center reveals that abnormal values for several recommended measures are uncommon. Thyroid screening was infrequently abnormal and the usefulness of screening for hepatitis B at diagnosis is uncertain. Similarly, our data suggest that iron deficiency screening may be condensed effectively into hemoglobin and ferritin testing, eliminating the need for initial iron studies. Decreasing baseline screening measures could safely decrease the burden of testing on patients and overall healthcare expenditures.

Abnormal Laboratory Values for Metabolic and Hormonal Syndromes Are Prevalent Among Patients Undergoing Rotator Cuff Repair

To determine the prevalence of systemic laboratory abnormalities among patients undergoing rotator cuff repair (RCR). Patients who underwent RCR at the authors' institution for 1 year between October 2021 to September 2022 were retrospectively identified. Preoperative laboratory values, including serum sex hormones, vitamin D, hemoglobin A1C, and a lipid panel, were obtained as part of our routine practice during the study period. Demographics and tear characteristics were compared in patients with laboratory data and those without. For included patients with laboratory data, mean laboratory values and percentage of patients with abnormal laboratory values were recorded. During a 1-year period of time, 135 RCRs were performed, of which preoperative labs were obtained on 105. Of these, 67% were sex hormone deficient, 36% were vitamin D deficient, 45% had an abnormal hemoglobin A1C, and 64% had an abnormal lipid panel. In total 4% had "normal" labs. In this retrospective study, sex hormone deficiency is highly prevalent among patients undergoing RCR. Nearly all patients undergoing RCR have systemic laboratory abnormalities involving either sex hormone deficiency, vitamin D deficiency, dyslipidemia, and/or prediabetes. Level IV, prognostic case series.

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

Abstract 5538: Prevalence of factors serving as common cancer clinical trial eligibility criteria by race and ethnicity

Abstract Background: Racial/ethnic minority patients remain underrepresented in clinical trials potentially due to restrictive trial eligibility criteria that disproportionally affect minority cancer patients. Objective: To examine the prevalence of existing medical conditions and abnormal lab values that commonly serve as clinical trial eligibility criteria among cancer patients by race and ethnicity. Methods: A cross-sectional analysis was conducted among patients new to Moffitt Cancer Center in 2011-2021 with multiple myeloma (n=3,967), breast (n=14,348), lung (n=10,492), and prostate (n=7,823) cancers. Demographics, existing medical conditions, and lab values were obtained from the Electronic Health Record, whereas history of cancer and metastatic disease at diagnosis were obtained from the Cancer Registry. Prevalence of medical conditions and abnormal lab values were reported among all patients and compared by race groups (White, Black, Hispanic, and other races) using age-adjusted logistic regression. For factors with prevalence higher than 5%, stratified analysis was conducted with respect to cancer type and adjusted for multiple comparisons. Results: Compared to White patients, Black (B) and Hispanic (H) patients were found to have higher prevalence of diabetes (OR [odds ratio] = 2.26 [B]/1.40 [H]), organ transplantation (OR=1.58 [B]/1.77 [H]), hepatitis (OR=1.74 [B]/1.48 [H]), HIV (OR=4.25 [B]/1.92 [H]), and abnormal creatinine value (OR=1.77 [B]/1.23 [H]). In addition, Black patients were more likely to have hypertension (OR=1.41) while patients of other races were more likely to be diabetic (OR=1.36). Similar patterns were observed across cancer types. Conclusion: Restrictive cancer clinical trial eligibility criteria may post a structural barrier that disproportionately impact racial/ethnic minority patients. Investigators should consider leveraging real-world data to define and design appropriate trial eligibility criteria. Prevalence of factors commonly included as clinical trial eligibility by race/ethnicity. Factors All White Black Hispanic Other Prevalence (%) % % OR (95% CI) % OR (95% CI) % OR (95% CI) Diabetes 6.30 5.90 10.00 2.26 (1.97-2.58) 6.50 1.40 (1.20-1.63) 6.50 1.36 (1.07-1.70) Chronic obstructive pulmonary disease 10.30 11.40 6.20 0.61 (0.52-0.72) 6.10 0.61 (0.52-0.71) 5.90 0.57 (0.44-0.72) Hypertension 18.00 18.50 19.80 1.41 (1.27-1.55) 13.40 0.87 (0.78-0.97) 13.50 0.84 (0.71-1.00) Heart condition 3.00 3.10 2.60 1.10 (0.86-1.39) 2.00 0.80 (0.61-1.03) 1.80 0.70 (0.44-1.05) Organ transplant 0.90 0.90 1.40 1.58 (1.11-2.20) 1.50 1.77 (1.28-2.41) 0.40 0.46 (0.16-1.00) Autoimmune disease 2.50 2.60 2.10 0.84 (0.63-1.09) 1.90 0.78 (0.59-1.01) 2.20 0.90 (0.60-1.30) Hepatitis 0.70 0.70 1.20 1.74 (1.17-2.49) 1.00 1.48 (0.99-2.15) 0.40 0.60 (0.21-1.30) HIV infection 0.30 0.20 0.90 4.25 (2.62-6.74) 0.40 1.92 (1.01-3.40) 0.20 0.71 (0.12-2.30) History of any cancer 15.90 17.20 10.30 0.69 (0.60-0.78) 10.30 0.69 (0.61-0.77) 10.90 0.71 (0.59-0.85) Metastasis at diagnosis 21.20 21.40 22.60 1.13 (1.02-1.24) 19.80 0.96 (0.87-1.05) 18.60 0.88 (0.75-1.02) Abnormal neutrophil count 19.70 20.10 20.20 1.00 (0.86-1.16) 16.60 0.79 (0.67-0.93) 18.20 0.89 (0.69-1.13) Abnormal creatinine 14.00 13.50 19.30 1.77 (1.57-1.99) 14.10 1.23 (1.08-1.39) 13.40 1.13 (0.93-1.38) Abnormal glomerular filtration rate 14.00 13.50 22.40 2.32 (1.99-2.70) 11.20 1.07 (0.88-1.30) 10.10 0.91 (0.66-1.22) Abnormal bilirubin 2.40 2.50 2.40 1.02 (0.69-1.45) 2.40 1.03 (0.70-1.46) 2.40 0.99 (0.52-1.69) Abnormal aspartate aminotransferase 9.40 9.40 9.20 0.88 (0.72-1.07) 9.70 0.92 (0.76-1.12) 8.50 0.82 (0.59-1.12) Citation Format: Yayi Zhao, Rossybelle P. Amorrortu, Rachel Howard, Kedar S. Kirtane, Susan T. Vadaparampil, Dana E. Rollison. Prevalence of factors serving as common cancer clinical trial eligibility criteria by race and ethnicity. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5538.

Abnormal preoperative leukocyte counts and postoperative complications following total shoulder arthroplasty

Total shoulder arthroplasty (TSA) has become the mainstay of treatment for degenerative glenohumeral arthritis, proximal humerus fracture, and rotator cuff arthropathy. The expanding indications for reverse TSA have increased the overall demand for TSA. This necessitates higher quality preoperative testing and risk stratification. White blood cell counts can be obtained from routine preoperative complete blood count testing. The association between abnormal preoperative white blood cell counts and postoperative complications has not been extensively studied. The purpose of this study was to investigate the association between abnormal preoperative leukocyte counts and 30-day postoperative complications following TSA. The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent TSA between 2015-2020. Patient demographics, comorbidities, surgical characteristics, and 30-day postoperative complication data were collected. Multivariate logistic regression was used to identify postoperative complications associated with preoperative leukopenia and leukocytosis. In this study, 23,341 patients were included: 20,791 (89.1%) were in the normal cohort, 1307 (5.6%) were in the leukopenia cohort, and 1243 (5.3%) were in the leukocytosis cohort. Preoperative leukopenia was significantly associated with higher rates of bleeding transfusions (P=.011), deep vein thrombosis (P=.037), and non-home discharge (P=.041). After controlling for significant patient variables, preoperative leukopenia was independently associated with higher rates of bleeding transfusions (odds ratios [OR] 1.55, 95% confidence intervals [CI] 1.08-2.23; P=.017) and deep vein thrombosis (OR 2.26, 95% CI 1.07-4.78; P=.033). Preoperative leukocytosis was significantly associated with higher rates of pneumonia (P<.001), pulmonary embolism (P=.004), bleeding transfusions (P<.001), sepsis (P=.007), septic shock (P<.001), readmission (P<.001), and non-home discharge (P<.001). After controlling for significant patient variables, preoperative leukocytosis was independently associated with higher rates of pneumonia (OR 2.20, 95% CI 1.30-3.75; P=.004), pulmonary embolism (OR 2.43, 95% CI 1.17-5.04; P=.017), bleeding transfusions (OR 2.00, 95% CI 1.46-2.72; P<.001), sepsis (OR 2.95, 95% CI 1.20-7.25; P=.018), septic shock (OR 4.91, 95% CI 1.38-17.53; P=.014), readmission (OR 1.36, 95% CI 1.03-1.79; P=.030), and non-home discharge (OR 1.61, 95% CI 1.35-1.92; P<.001). Preoperative leukopenia is independently associated with higher rates of deep vein thrombosis within 30 days following TSA. Preoperative leukocytosis is independently associated with higher rates of pneumonia, pulmonary embolism, bleeding transfusion, sepsis, septic shock, readmission, and non-home discharge within 30 days following TSA. Understanding the predictive value of abnormal preoperative lab values will aid in perioperative risk stratification and minimize postoperative complications.

Laboratory Findings of Benign Convulsions With Mild Gastroenteritis: A Meta-Analysis.

Investigating factors associated with benign convulsions with mild gastroenteritis (CwG) is important for early detection and treatment. In previous studies, uric acid (UA) has been reported to be associated with CwG. However, the association between CwG and abnormal laboratory values remains inconclusive. We performed a meta-analysis of recent reports to determine the association between CwG and laboratory findings, including UA, in patients with acute gastroenteritis without convulsions. We conducted electronic searches of three databases (PubMed, EMBASE, and Cochrane Library) and one scholarly search engine (Google Scholar (Google, Inc., Mountain View, CA, USA)) up to February 2023 for studies on CwG. Eligible studies were observational studies that assessed patients with CwG, reported laboratory data, and stated the presence or absence of convulsions during illness episodes. Patients were children with mild gastroenteritis, with the exposure group developing convulsions and the control group not. The outcome was a comparison of laboratory data between the two groups. The effect size was calculated using the standardized mean difference (SMD), and random-effects models were used for the analysis because of high heterogeneity. In total, 148 articles were included in this study. After the screening, nine studies, including 8,367 patients, were selected for the meta-analysis. The most prevalent laboratory finding was an increased serum UA level, with an SMDof 1.42(N = 6,411; 95% confidence interval (CI): (1.12, 1.72); Z = 9.242, p< 0.001;I 2 = 81.68%, p= 0.002). The optimal serum UA cutoff value was 7.21 mg/dL, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.827 (95% CI: (0.807, 0.846)). This meta-analysis suggests that CwG is strongly associated with increased serum UA levels. These results demonstrate that more attention should be paid when interpreting laboratory findings in pediatric patients with acute gastroenteritis.

Applicability of International Autoimmune Hepatitis Group (IAIHG) Scoring System for Autoimmune Hepatitis in Pediatrics.

Many hepatologic pathologies mimic autoimmune hepatitis (AIH). Researchers developed the International Autoimmune Hepatitis Group (IAIHG) scoring system to compensate for the lack of specific diagnostic tests for AIH. The scoring system was not designed with pediatric patients in mind, so there are limits to its pediatric use. Additionally, there is limited information on the value of a liver biopsy in conjunction with its use. In this retrospective study, we evaluated the effect of liver biopsy scores on the IAIHG scoring system in patients that were 0-18 years old with suspected AIH. We also analyzed demographic data and laboratory values associated with a final AIH diagnosis. We found that interface hepatitis and predominant plasma cells found during the biopsy were significantly associated with a final AIH diagnosis. We also found that abnormal laboratory values were associated with an AIH diagnosis. We found that IAIHG scores calculated post-liver biopsy showed a greater area under the receiver operating characteristic curve (AUROC) of 0.95, which was compared to 0.88 for the scores calculated before a liver biopsy. Including biopsy metrics lowered the optimized cutoff score and test specificity. Incorporating liver histopathological features improved the performance of the IAIHG scoring system. Further studies to identify other potential elements in liver histology may improve the performance metrics of the IAIHG test in the pediatric population.

A82 PREVALENCE AND NON-INVASIVE SCREENING FOR CYSTIC FIBROSIS RELATED LIVER DISEASE IN A COHORT FOLLOWED AT A CYSTIC FIBROSIS REFERENCE CENTER

Abstract Background The reported prevalence of cystic fibrosis (CF) related liver disease (CFLD) varies widely based on diagnostic criteria but reaches up to 40% in some cohorts. Furthermore, its clinical impact is significant as hepatic involvement is the 3rd leading cause of mortality in CF patients and is associated with a lower life expectancy. Due to the heterogeneous clinical presentation of CFLD, clear diagnostic criteria and non-invasive assessment methods are lacking. Purpose This study aimed to measure the prevalence of CFLD in a cohort of patients followed at a tertiary CF center. Method The files of all patients followed at the CF clinic of the Centre hospitalier de l’Université de Montréal in 2021 were retrospectively reviewed. Imaging reports, histopathology, laboratory values and transient elastography results were assessed. The NIH criteria were used to define CFLD through either presence of one major criteria (abnormal imaging) or two minor criteria (persistently abnormal lab values, hepatosplenomegaly, or transient elastography ≥ 7 kPa). Result(s) 358 patients were included in our study, 56% male with a median age of 36 years. While mean liver tests were within normal limits (ALT 24 U/L, AST 26 U/L, ALP 96 U/L, GGT 29 U/L), 182 patients (51%) had at least one episode of abnormal liver function tests (LFTs), and 85 patients (24%) had persistently abnormal LFTs. CFLD was present in 42 patients (12%), with 39 patients presenting major criteria and 3 patients presenting minor criteria. In addition, 67 patients (19%) had solely hepatic steatosis. Furthermore, clinically significant portal hypertension and esophageal varices were detected in 50% of patients with CFLD who underwent upper endoscopy (n=20). Median transient elastography value was 5.4 kPa (interquartile range 4.25 kPa) in the 51 patients with exam results, and 32% had values ≥ 7 kPa. Fibroscan values correlated well with the presence of major criteria, with an area under the curve (AUROC) of 0.80 (0.68-0.92, p=0.0007), while non-invasive serological markers did not perform as well (Fib4: AUROC 0.70 (0.59-0.81) and APRI: AUROC 0.69 (0.59-0.80)). Conclusion(s) The overall prevalence of CFLD, including hepatic steatosis, was 31% in this cohort. Prompt recognition is important in clinical care in order to prevent hepatic complications from cirrhosis and portal hypertension. The use of Fibroscan seems promising for detecting CFLD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Preoperative demographics and laboratory markers may be associated with early dislocation after total hip arthroplasty

PurposeThe purpose of this study was to identify modifiable medical comorbidities, laboratory markers and flaws in perioperative management that increase the risk of acute dislocation in total hip arthroplasty (THA) patients.MethodsAll THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Demographic data, preoperative laboratory values, recorded past medical history, operative details as well as outcome and complication information were collected. The study population was divided into two cohorts: non-dislocation and dislocation patients. Statistics were performed to compare the characteristics of both cohorts and to identify risk factors for prosthetic dislocation (α < 0.05).Results275,107 patients underwent primary THA in 2007 to 2020, of which 1,258 (0.5%) patients experienced a prosthetic hip dislocation. Demographics between non-dislocation and dislocation cohorts varied significantly in that dislocation patients were more likely to be female, older, with lower body mass index and a more extensive past medical history (all p < 0.05). Moreover, hypoalbuminemia and moderate/severe anemia were associated with increased risk of dislocation in a multivariate model (all p < 0.05). Finally, use of general anesthesia, longer operative time, and longer length of hospital stay correlated with greater risk of prosthetic dislocation (all p < 0.05).ConclusionsElderly female patients and patients with certain abnormal preoperative laboratory values are at risk for sustaining acute dislocations after index THA. Careful interdisciplinary planning and medical optimization should be considered in high-risk patients as dislocations significantly increase the risk of sepsis, cerebral vascular accident, and blood transfusions on readmission.

Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high-dose methotrexate based on individual pharmacokinetics: A retrospective study.

In the high-dose methotrexate (HD-MTX) treatment of patients with osteosarcoma, a dose-adjustment method using individual pharmacokinetic parameters (PK method) to optimize the concentration was developed in 2010. However, to the best of our knowledge, the clinical usefulness of the PK method has not been verified until now. In the present retrospective study, to assess the usefulness of the PK method, the achievement rate of an effective and safe concentration range was evaluated. A total of 43 patients with osteosarcoma who were administered HD-MTX therapy (43 first courses and 200 subsequent courses) were enrolled. The MTX dose in the first course was determined using a common method based on body surface area (BSA method); a total of 8-12 g/m2 was administered as an initial dose for 1 h and a maintenance dose for 5 h. In the subsequent courses, loading and maintenance doses were calculated by the PK method based on the serum MTX concentration profile of the previous course. The effective target concentration during 1-6 h after the start of MTX administration was 700-1,000 µmol/l, whereas the target safe MTX level was less than 10, 1 and 0.1 µmol/l at 24, 48 and 72 h, respectively. Notably, the rate of achieving the effective target concentration was significantly higher when using the PK method as compared to that when using the BSA method. The achievement rate of the safe target concentration at 24, 48 and 72 h when using the PK method was significantly higher. Additionally, the incidence of abnormal laboratory values of aspartate aminotransferase and alanine aminotransferase was significantly lower when using the PK method. Therefore, the PK method was suggested to be very useful in HD-MTX therapy for patients with osteosarcoma.

1071: QUANTIFYING PASSIVE CLINICAL DECISION SUPPORT AND REDUCING LABORATORY RESULT FATIGUE

Introduction: Clinical decision support (CDS) systems are intended to improve adherence to standard practices, enhance awareness, and increase care quality. Excessive passive decision support, such as laboratory result highlighting, can reduce CDS effectiveness. We quantify result highlighting burden across two institutions, and measure change in highlighting burden when applying published data-driven cutoffs to identify abnormal laboratory values. Methods: This multi-site retrospective study includes patients admitted to the pediatric ICU between 9/2016 and 9/2019. We describe the frequency of abnormal laboratory result highlighting by laboratory group, compared across sites. We use a logistic regression model to analyze the relationship between abnormal result highlighting to selected covariates and report odds ratios. We apply modified cutoff values based on mortality odds ratios (MOR) [Pollack et al, Peds Crit Care Med, 2021], indicating “abnormal” results when MOR >2.0. We re-calculate the frequency of abnormal result highlighting and compare to existing cutoffs. Results: We report a total of 19,087 ICU encounters and 12,507 unique patients. Across all laboratory groups, abnormal result highlighting differed significantly by institution (A: 54% vs B: 50%, p < 0.001). Percent of results with passive alerts was greatest in coagulation studies (A: 77%, B: 36%) and least in basic chemistry panels (A: 47%, B: 43%). In a logistic regression model, the only covariate consistently associated with an abnormal result was “collected < 24 hours from ICU admission,” for which odds of an abnormal result decreased [A: 12% decrease; B: 15% decrease]. When MOR-based cutoffs were applied, abnormal result highlight significantly decreased across all laboratory groups by >14%, except for complete blood counts (A: 14% increase, B: 16% increase). Conclusions: Abnormal result highlighting is a pervasive form of passive decision support that is differentially present across PICUs. Modifying laboratory result thresholds using data-driven MOR-based cutoffs reduces this passive CDS burden, which may better allow providers to identify physiologic signals from data noise. This work represents a first step in improving upon passive CDS to improve patient care quality and safety.

A case of duodenal diverticulitis in a patient receiving tocilizumab for rheumatoid arthritis

A Japanese woman was diagnosed with rheumatoid arthritis at the age of 41. At the age of 56, her rheumatoid arthritis worsened and a subcutaneous injection of tocilizumab and oral prednisolone was administered, which led to an improvement of arthritis. At the age of 57, right lower abdominal pain and vomiting suddenly appeared. Abdominal computed tomography showed a parapapillary diverticulum in the descending duodenum. The diverticulum was filled with residue, and an inflammation of the surrounding adipose tissue was observed; no free air was found. The patient was diagnosed with duodenal diverticulitis and treated with antibiotics, which resulted in an uneventful recovery. The maximum value of CRP was 1.88㎎/dL on the third day of hospitalization. Esophagogastroduodenoscopy performed on the 8th day of hospitalization revealed a parapapillary diverticulum with adhesion of pus and redness of the mucosa at the opening of the diverticulum, consistent with diverticulitis. This case highlights that diverticulitis in infrequent areas such as the duodenum may occur in patients who are treated with tocilizumab. In addition, inflammation of diverticulitis may be underestimated because abnormal laboratory values such as those induced by inflammatory reactions are less likely to occur during tocilizumab treatment.

Results From a Multiple Ascending Dose Study in Healthy Volunteers of ACD856, a Positive Modulator of Neurotrophin Trk‐Receptors

AbstractBackgroundACD856 is a novel positive allosteric modulator of Trk‐receptors in clinical development for the treatment of Alzheimer’s disease and other disorders where cognition is impaired. The aim of this study was to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple ascending doses of ACD856.Method24 healthy volunteer subjects were administered ACD856 or placebo as a daily oral solution over 7 days in 3 cohorts of stepwise ascending doses. After each dose, the safety, tolerability, and pharmacokinetics of ACD856 were assessed by an internal Safety Review Committee to decide on the escalation of dose to the next cohort.ResultThere were no clinically significant changes from baseline in mean ECG, vital signs, physical examination findings, clinical chemistry, haematology, coagulation, or urinalysis parameters after receiving the 7 daily doses of ACD856. Occasional individual abnormal laboratory values were observed but all were assessed as not clinically significant. Most of the reported adverse events were of mild intensity, only a few were of moderate intensity and none of severe intensity. No serious adverse events were reported.The pharmacokinetic data confirmed the findings from the previously performed single ascending dose (SAD) study, including that ACD856 has a rapid absorption, long half‐life, high bioavailability, and a linear dose‐dependent exposure. The Cmax at steady state was approximately 1.6‐fold higher than the initial dose administration and no time‐dependent clearance was observed. Moreover, initial CSF data confirms CNS exposure of ACD856. Further PK, CSF and pharmacodynamic data will be shown at the time of presentation.ConclusionACD856 was shown to be safe and well tolerated in man at the tested dose levels and with a suitable pharmacokinetic profile for further clinical development. In the next step, ACD856 will be evaluated in a phase Ib study with the aim to further assess pharmacodynamic effects.