Complete Panel Research Articles

Peripheral Inflammatory and Metabolic Markers as Potential Biomarkers in Treatment-Resistant Schizophrenia: Insights from a Qatari Cohort.

Schizophrenia presents significant diagnostic and treatment challenges, particularly in distinguishing between treatment-resistant (TRS) and non-treatment-resistant schizophrenia (NTRS). This cross-sectional study analyzed routine laboratory parameters as potential biomarkers to differentiate TRS, NTRS, and healthy individuals within a Qatari cohort. The study included 31 TRS and 38 NTRS patients diagnosed with schizophrenia, alongside 30 control subjects from the Qatar Biobank. Key measurements included complete blood count, lipid panel, HbA1c, and ferritin levels. Our findings indicated elevated body mass index (BMI) and triglyceride (TG) levels in both patient groups compared to controls. The NTRS group also showed higher HbA1c levels. Variations in inflammatory markers were noted, with the NTRS group exhibiting a higher platelet/lymphocyte ratio (PLR). Multivariate analysis highlighted significant differences in platelet count, mean platelet volume (MPV), TG, HbA1c, BMI, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and ferritin among the groups. Linear regression analysis revealed that MLR and clozapine treatment were significantly correlated with the severity of schizophrenia symptoms. The Random Forest model, a supervised machine learning algorithm, efficiently differentiated between cases and controls and between TRS and NTRS, with accuracies of 86.87% and 88.41%, respectively. However, removing PANSS scores notably decreased the model's diagnostic effectiveness. These results suggest that accessible peripheral laboratory parameters can serve as useful biomarkers for schizophrenia, potentially aiding in the early identification of TRS, enhancing personalized treatment strategies, and contributing to precision psychiatry. Future longitudinal studies are necessary to confirm these findings and further explore the role of inflammation in schizophrenia pathophysiology and treatment response.

Racial differences in laboratory testing as a potential mechanism for bias in AI: A matched cohort analysis in emergency department visits.

AI models are often trained using available laboratory test results. Racial differences in laboratory testing may bias AI models for clinical decision support, amplifying existing inequities. This study aims to measure the extent of racial differences in laboratory testing in adult emergency department (ED) visits. We conducted a retrospective 1:1 exact-matched cohort study of Black and White adult patients seen in the ED, matching on age, biological sex, chief complaint, and ED triage score, using ED visits at two U.S. teaching hospitals: Michigan Medicine, Ann Arbor, MI (U-M, 2015-2022), and Beth Israel Deaconess Medical Center, Boston, MA (BIDMC, 2011-2019). Post-matching, White patients had significantly higher testing rates than Black patients for complete blood count (BIDMC difference: 1.7%, 95% CI: 1.1% to 2.4%, U-M difference: 2.0%, 95% CI: 1.6% to 2.5%), metabolic panel (BIDMC: 1.5%, 95% CI: 0.9% to 2.1%, U-M: 1.9%, 95% CI: 1.4% to 2.4%), and blood culture (BIDMC: 0.9%, 95% CI: 0.5% to 1.2%, U-M: 0.7%, 95% CI: 0.4% to 1.1%). Black patients had significantly higher testing rates for troponin than White patients (BIDMC: -2.1%, 95% CI: -2.6% to -1.6%, U-M: -2.2%, 95% CI: -2.7% to -1.8%). The observed racial testing differences may impact AI models trained using available laboratory results. The findings also motivate further study of how such differences arise and how to mitigate potential impacts on AI models.

Biochemical variables as predictors of in-hospital mortality in patients with acute coronary syndrome

Abstract Background There is a constant search of easily obtainable variables that can be put in relation with in-hospital mortality, enabling creation of prediction risk models in patients treated for acute coronary syndrome. Purpose The main goal of this study was to unravel what is the profile of the patients with acute coronary syndrome in risk of in-hospital mortality, based on simple biochemical variables acquired at the time of hospital admission. Methods This was a single-center cross-sectional cohort study on 3007 pts. treated for ACS (STEMI and NSTEMI). Venous blood sample at hospital admission was acquired for every patient. Patients were comparatively analyzed for their biochemical variables derived from venous blood sample, based on occurrence of in-hospital mortality. Results Out of 3007 pts, 988 (28.2%) were females, and 2519 (71.8%) males, at mean age 62.6 +/- 11.2 y. In-hospital mortality rate was 4.8% (145 out of 3007). We subjected to comparative analyzed hemogram, markers of renal function including sodium and potassium, glycemic profile, complete lipid panel (including ApoA1 and ApoB), and highly sensitive troponin. Significant association with in-hospital mortality was found for: hsTn, stress glycemia and glicated hemoglobin, BUN, creatinite, eGFR, sodium, potasium, full lipid panel [except for HDL-C and Lp(a)]. In the second step, markers proven to be significantly different were subjected to multivariate binary logistic regression (backward conditional). We designed two models, one that included ApoA1 and ApoB (including 1816 pts. for whom we had data), and the second without these two parameters (including 3007 pts.). With the first model we identified: Advanced age, stress glycemia, WBC, eGFR, HDL-C and ApoA1 as independent predictors. Surprisingly, HDL-C was found to be strong independent predictor in multivariate analyzis. While with second modeling we identified advanced age, hsTn, stress glycemia, RBC, WBC, BUN and eGFR as independent predictors. Conclusion Advanced age is a strong independent predictor in any modelling. When we have a possibility to obtain a complete lipid panel, beside stress glycemia and WBC as markers of the degree of neuro-hormonal activation and inflammation, and renal function, HDL-C and ApoA1 seems to be strong negative independent predictors. In the absence of this data beside aforementioned markers of neurohormonal activation and inflammation, and renal function, the degree of myocardial injury plays a significant role. According to our data it seems reasonable to obtain complete lipid panel at hospital admission.Multivariate logistic regression modelsAge distribution across genders

Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention

Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction. Purpose To examine ASCVD risk by composition of non-HDL-C. Methods Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022. Results The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups. Conclusions The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2

Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII.

PCI-27483, originally developed as a potent and selective inhibitor of the serine protease Factor VIIa (FVIIa) in complex with tissue factor (TF), has demonstrated significant promise in cancer therapy. In addition to its primary mechanism of action, the presence of a sulfonamide moiety in the PCI-27483 structure suggests further activities through the inhibition of carbonic anhydrases (CAs), particularly the tumor-associated human (h)CA isoforms hCA IX and XII. This study investigates the inhibitory activity of PCI-27483 against the complete panel of active hCAs, highlighting its polypharmacological potential in cancer treatment. X-ray crystallography and molecular docking studies elucidated the structural features underlying its selective inhibitory activity toward hCA IX and XII, offering insights into its dual-targeting pathway.

DICER1 Mutations Enable Rare Tumor Formation

Abstract Introduction/Objective DICER1 is a tumor suppressor gene that imparts a slight increase in tumor formation when mutated. The protein plays a role in processing miRNA that silences transcription. Germline mutations of DICER1 predispose to tumors in a known set of organs and rarely in other locations. However the presence of additional genetic aberrations further increases the likelihood of tumor formation. Acting as a compounding factor, DICER1 mutations can present a constantly shifting cancer phenotype of affected patients. Of particular interest here is the development of both Pineoblastoma and Malignant spindle cell sarcoma in a young patient. Sarcomas are estimated to make up only 10% of pediatric cancers and Pineal masses only 3%. Methods/Case Report This case involves an 8 year old male with a history of Pineoblastoma who originally presented with slowly worsening ataxia. A screening ultrasound on following visits identified an abdominal mass that was confirmed with computed tomography. Subsequent biopsies showed malignant spindle cells arranged in a herringbone pattern. Additionally these cells displayed high mitotic activity and hyperchromatic nuclei. Surprisingly, they also demonstrated extramedullary hematopoiesis. Multiple stains were performed however no significant conclusion could be made. The appearance of this tumor and its rarity prompted a request for a Complete Comprehensive Sarcoma Panel via Next Generation Sequencing. This confirmed the presence of pathologic BRAF and DICER1 genes. From that the diagnosis of DICER1 associated Malignant Spindle Cell Sarcoma was made. BRAF V600E is the most common genetic variant and is seen in multiple cancers but only seen in 1-3% of sarcomas. Pathologic variants of the DICER1 gene exist on exons 13 and 25. The presence of these exon mutations in some way affect DICER1 protein function and compound the effects of the mutated BRAF gene. This situation is unique as such neoplasms are rarely found in the anterior abdominal wall and showcases the effects of DICER1 on rare tumor phenotypes. Results (if a Case Study enter NA) NA Conclusion Continuing research into both DICER1 protein pathways is essential for isolating a diagnosis and guiding treatment. It would seem screening images and genetic testing would benefit pediatric or even adult patients with common and rare cancers. Extra effort made toward this would not be outside the norm as personalized medicine is gradually becoming the standard for cancer treatment.

9396 Deciphering The Enigma: A Case Report On New-onset Graves Disease Presenting As Thyroid Storm In The First Trimester Of Pregnancy, Managed In The Intensive Care Setting

Abstract Disclosure: M. Zeb: None. S.W. Salari: None. A. Tiwari: None. A. Vadher: None. A. Dabaja: None. S. Kambhatla: None. Graves' disease, an autoimmune disorder characterized by hyperthyroidism, presents unique challenges when manifesting as thyroid storm during pregnancy. We report a case of a 27-year-old African American woman at 9 weeks gestation who presented with palpitations, agitation, and fever. On examination, she exhibited fever, tachycardia, tremors in hands, and mild bilateral exophthalmos. Thyroid function tests revealed markedly elevated free thyroxine and suppressed thyroid-stimulating hormone levels. Thyroid ultrasound confirmed diffuse thyroid enlargement with increased vascularity, consistent with Graves' disease. Pelvic ultrasound estimated the gestational age at 9 weeks and 2 days, with a serum β-hCG level of 135,037 mIU/mL. An electrocardiogram revealed sinus tachycardia, and a complete metabolic panel indicated mild hypokalemia. The Thyroid Stimulation Immunoglobulin (TSI) and Thyrotropin receptor antibodies were tested positive. The Burch-Warsofsky point score of 45, supported the diagnosis of thyroid storm. The patient received intensive care treatment including intravenous fluids, hydrocortisone, beta-blockers, Lugol’s iodine, propylthiouracil, and potassium replacement. Following treatment, thyroid function stabilized within 48 hours, and her hyperthyroid symptoms resolved. The patient was discharged on oral labetalol and propylthiouracil. Thyroid storm, characterized by severe manifestations of hyperthyroidism, is a rare but potentially life-threatening condition, especially during pregnancy. Prompt recognition and intervention are crucial due to associated maternal and fetal morbidity and mortality. A multidisciplinary approach, involving endocrinology, obstetrics, and critical care, is essential to optimize outcomes. The unique physiologic changes of pregnancy, such as increased thyroid hormone production and altered thyroid hormone-binding globulin levels, can complicate the diagnosis and management of hyperthyroidism. Our case underscores the importance of vigilance for thyroid dysfunction in pregnant women, even in the absence of prior thyroid disease. Additionally, the potential impact of hyperthyroidism and thyroid storm on pregnancy outcomes highlights the need for early recognition and intervention. Long-term management of Graves' disease during pregnancy may also require adjustment of antithyroid medication dosage and monitoring of thyroid function to maintain euthyroidism while minimizing fetal exposure to medication. Further research is warranted to refine diagnostic criteria, treatment protocols, and long-term management strategies for thyroid storm in pregnancy. Increased awareness among healthcare providers about the risks and management strategies for this rare but serious complication is also necessary. Presentation: 6/3/2024

Red cell distribution width and mean platelet volume detection in patients with endometrial cancer and endometrial hyperplasia.

Endometrial cancer is the most common malignancy in women in developed countries, and its incidence is increasing annually. Due to the availability and cost-effectiveness of serum markers of red cell distribution width (RDW), and mean platelet volume (MPV), we decided to investigate these two important markers in patients with endometrial cancer and assess their role in diagnosing the tumor and differentiate it from endometrial hyperplasia and other causes of bleeding. This is a case-control study that examined the data of patients who were referred to Al-Zahra Hospital during 2022-2023 with complaints of abnormal bleeding and underwent diagnostic curettage. Based on the pathology findings, the patients were divided into 3 groups, including endometrial cancer, endometrial hyperplasia, and control. The clinical characteristics and results of MPV and RDW were compared in these three groups. The IBM SPSS Statistics for Windows, Version 21.0. was used for data analysis. In this study, 87 women were examined in three groups endometrial cancer, endometrial hyperplasia, and control with a mean age of 52.70 ± 11.63 years. The results showed that the endometrial cancer group, had higher gravida, underlying disease, history of radiation therapy, anticoagulant therapy, blood transfusion, surgery, and family history of cancer (p < 0.05). Meanwhile, the endometrial cancer group had lower menstrual age and history of using contraceptives than other groups (p < 0.05). In addition, in this study, the results indicated that the levels of MPV and RDW in the endometrial cancer group were significantly higher than in the endometrial hyperplasia and control groups (p < 0.05). Since MPV and RDW are cheap and accessible and can be easily obtained from complete blood count panels, they can be used as suitable diagnostic markers for endometrial cancer. However, conducting comprehensive multicenter prospective studies with a larger sample size can be helpful.

413 (PB401): Comprehensive characterization of CDK inhibitors using a complete panel of all 20 human cyclin-dependent kinases

413 (PB401): Comprehensive characterization of CDK inhibitors using a complete panel of all 20 human cyclin-dependent kinases

DIAGNOSTIC YIELD OF AN INHERITED RETINAL DISEASE GENE PANEL IN RETINOPATHY OF UNKNOWN ORIGIN.

Evaluating the presence of class 3, 4, and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO). Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmologic history, complete ophthalmologic examination, antiretinal antibodies, and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: nonparaneoplastic autoimmune retinopathy, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy. The authors included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20-68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, two also demonstrated class 5 variants in other IRD genes. The remaining five patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) nonparaneoplastic autoimmune retinopathy patient in the RUO cohort. When considering the nonparaneoplastic autoimmune retinopathy subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved. Every suspected nonparaneoplastic autoimmune retinopathy patient should benefit from gene panel testing to not overlook undiagnosed IRDs. By contrast, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy subpopulations did not benefit from genetic testing in this study.

Presumptive West Nile Virus Infection in a Komodo Dragon ( Varanus komodoensis )

Abstract A 3-yr-old, male Komodo dragon (Varanus komodoensis) presented acutely in early October 2021 with an abnormal posture and asymmetric tetraparesis. The subadult lizard had spent the previous 4 months either in an outdoor space or in an indoor space with open windows. Physical examination, radiographs, and complete blood count and chemistry panel failed to reveal the cause of the neurologic signs. West Nile virus (WNV) plaque reduction serum neutralization on presentation was negative (1:20), as was WNV polymerase chain reaction (PCR) testing and viral isolation on whole blood. Empirical treatment with a daily corticosteroid, course of antibiotics, and encouragement of mild exercise was initiated. Magnetic resonance imaging of the brain and spinal cord was unremarkable, and a lumbar cerebrospinal fluid (CSF) tap revealed a mononuclear pleocytosis and protein elevation. Follow-up WNV serology revealed rising titer and seroconversion 13 days after presentation (1:80) and 32 days after presentation (1:640); however, WNV PCR testing of CSF fluid was negative. Thi Komodo dragon gradually improved over six weeks before being put back on public display 74 days after presentation. The WNV titer remained high (1:640) through the winter of 2021-22, and an anamnestic response was observed following a vaccination series with a killed equine vaccine in the spring of 2022. There is a previous brief report of WNV infection in a captive crocodile monitor (Varanus salvadorii), and an unpublished case in the same species at the first author’s institution. This is the first report of neurologic disease from presumptive WNV infection in a Komodo dragon. We recommend that WNV infection be a differential diagnosis if a varanid lizard present with acute neurologic signs with a history of arthropod vector exposure, particularly in the summer or fall.

Abstract Mo102: Swine Model of Heart Failure with Preserved Ejection Fraction Driven by Lipoprotein Lipase Inhibition and Enhanced Cardiac Low-Density Lipoprotein Receptor Expression

Background: Heart failure with preserved ejection fraction (HFpEF) poses an escalating public health threat, marked by growing incidence and high mortality. In the cardiometabolic phenogroup of HFpEF that includes diabetes and obesity, intramyocardial lipid content is a prognostic indicator of diastolic dysfunction and adverse outcome. Our group recently reported a mouse model of cardiometabolic HFpEF wherein myocardial lipotoxicity was induced by systemic inhibition of lipoprotein lipase (LPL) with Poloxamer 407 (P407) and cardiac overexpression of the LDL receptor (LDLR), conditions that have been documented in clinical HFpEF. The model demonstrates myocardial lipid accumulation, fibrosis, arrhythmia, and diastolic dysfunction. To reproduce this model in large animals we implemented the same protocol in pigs. Methods: Female Yorkshire swine (~25 Kg) were subjected to one of two protocols including: 1) single intracoronary (i.c.) injection of 10 13 AAV9-cTnT-LDLR particles and biweekly intraperitoneal (i.p.) P407 at 1g/Kg, (high dose, n=2), or 2) Double i.c. injections of 10 13 AAV9-cTnT-LDLR particles and biweekly i.p. P407 at 0.25g/Kg) (low dose, n=2). Cardiac structure and function were evaluated by MRI, and hemodynamics measured by PV-Loop at baseline, 4, 8, and 12 weeks. Blood was collected biweekly for complete blood count (CBC), basic biochemistry, and liver and lipid panels. Tissues were collected for protein and histopathological analysis. Results: In both strategies, the animals developed high LDL-cholesterol and cardiac hypertrophy with preserved EF. High dose P407 led to higher triglycerides, VLDL, HDL, liver injury (ALT &gt; 200U/L), and steatosis at 4 weeks. One of the 2 pigs died at 3 weeks. Low dose P407 and high dose viral particles induced HFpEF at ~12 weeks with increased LV mass, relative wall thickness, end-diastolic pressure, and tau. Serum LDL-C accumulated from an initial value of 161 to 344.5mg/dL at 12 weeks. No significant liver injury was present until week 12 (ALT&lt;88 U/L, AST&lt;59 U/L). Both strategies did not exhibit abnormalities in CBC or other biochemical parameters. Conclusions: Low dose inhibition of LPL combined with cardiac overexpression of LDLR confers HFpEF in swine.

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.

How to commit aging workers: the role of HR bundles

Since workforces are aging worldwide, scientists and practitioners aim at understanding the potential contribution of (bundles of) HR practices in increasing commitment among aging workers. In this time-lagged survey study, we distinguished four HR bundles for aging workers (Kooij et al., 2014a; Van Dalen et al., 2015): development, maintenance, utilization, and accommodative HR practices. We investigated the influence of the availability and use of these HR bundles on commitment over time and the role of age in this relationship. Based on two-wave complete panel data (N = 489) collected among employees in a Dutch university, we found that perceived availability of maintenance HR practices was positively associated with commitment over time. Further, based on the Selection, Optimization, and Compensation model (Baltes & Baltes, 1990), we expected and found that the relationship of the perceived availability and the perceived usage of utilization HR practices with commitment strengthens with age. These results highlight the importance of different bundles of HR practices for increasing commitment over time among aging workers.

A complete chromosome substitution mapping panel reveals genome-wide epistasis in Arabidopsis

Chromosome substitution lines (CSLs) are tentatively supreme resources to investigate non-allelic genetic interactions. However, the difficulty of generating such lines in most species largely yielded imperfect CSL panels, prohibiting a systematic dissection of epistasis. Here, we present the development and use of a unique and complete panel of CSLs in Arabidopsis thaliana, allowing the full factorial analysis of epistatic interactions. A first comparison of reciprocal single chromosome substitutions revealed a dependency of QTL detection on different genetic backgrounds. The subsequent analysis of the complete panel of CSLs enabled the mapping of the genetic interactors and identified multiple two- and three-way interactions for different traits. Some of the detected epistatic effects were as large as any observed main effect, illustrating the impact of epistasis on quantitative trait variation. We, therefore, have demonstrated the high power of detection and mapping of genome-wide epistasis, confirming the assumed supremacy of comprehensive CSL sets.

The role of lipidic balance on erectile dysfunction in prostate cancer patients undergoing robotic surgery.

New indices of dyslipidemia, such as the Atherogenic Index of Plasma (AIP) or Castelli Risk Index I and II (CR-I/II), have been tested to predict erectile dysfunction (ED). The aim of this study was to assess the role of these lipidic scores in predicting severe ED and erectile function (EF) worsening in patients who underwent robot-assisted radical prostatectomy (RARP). Data from 1249 prostate cancer patients who underwent RARP at our single tertiary academic referral center from September 2021 to April 2023 were reviewed. RARP patients with a complete lipid panel were included in the final analysis. Two independent multivariable logistic regression models (LRMs) were fitted to identify predictors of ED severity and worsening in RARP patients. Among the 357 RARP patients, the median age was 70 (interquartile range [IQR]: 65-74), and the median BMI was 28.4 (IQR: 26-30.4). According to the preoperative IIEF5, 115 (32.2%), 86 (24.5%), 26 (7.3%), and 40 (11.2%) were mild, mild-moderate, moderate, and severe ED patients, respectively. After multivariable LRMs predicting severe ED, only the nerve-sparing (NS) approach (odds ratio [OR]: 0.09) as well as the preoperative IIEF5 score (OR: 0.32) were independent predictors (p < 0.001). After LRMs predicting EF worsening, only preoperative IIEF5 was an independent predictor (OR: 1.42, p < 0.001). The power of novel lipidic scores in predicting severe ED and EF worsening in RARP patients was low, and they should not be routinely applied as a screening method in this patient subgroup. Only preoperative IIEF5 and nerve-sparing approaches are relevant in EF prediction after RARP.

P-275 Advanced hemostasis assessment in endometriosis: strengthening confidence in the safety of hormonal treatments

Abstract Study question Are women with endometriosis in a state of systemic imbalance between pro- and anti-coagulants? Summary answer Women with endometriosis do not seem to exhibit a coagulation imbalance, at least at a systemic level. What is known already A state of platelet hyperactivation potentially leading to a hypercoagulation status has been described in women with endometriosis. This phenomenon could induce an altered local environment, promoting platelet-mediated paracrine changes in endometrial tissue and also increasing cardiovascular risk, which could be worsened by the use of estrogen dependent hormonal treatments. However, despite a slight difference in some coagulation parameters has been observed between women affected and controls, their levels remain, generally, within the normal reference range. Study design, size, duration This prospective case-control study including 101 women seeking infertility consultation at the Infertility Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano between January and July 2023 aimed to assess hemostasis function beyond traditional coagulation parameters. Participants/materials, setting, methods Blood of women with endometriosis (n = 51) or tubal or male factor infertility (controls; n = 50) was obtained before any ART treatment, and a complete panel of coagulation tests were performed, including basic parameters (aPTT, PT, FVIII, FII, PC, AT, FIV-C, DD, vWF, ADMT) as well as more sophisticated ones, such as Thrombin Generation Assay and Thromboelastometry, providing data on endogenous thrombin potential (ETP), clot formation time (CFT) and maximal clot firmness (MCF). Main results and the role of chance There were no significant differences between cases and controls in terms of age (37 [34-39] vs 36 [33-39]; p = 0.53, respectively) and smoking habits (14% vs 28%; p = 0.14, respectively). Women affected had a lower BMI compared to controls (22.7 [20.9-24.9] vs 21.4 [19.6-23.8]; p = 0.03), as it is usually expected. Results from TGA were expressed as ETP ratio (with-/without- thrombomodulin), and high ones were indicative of thrombomodulin resistance, taken as indexes of procoagulant imbalance; however, it was not different between women with and without the disease (0.75 [0.65-0.82] vs 0.75 [0.66-0.82]; p = 0.82, respectively). Other markers of procoagulant imbalance evaluated by thromboelastometry were also similar between cases and controls, including CFT (66 sec [58-78] vs 65 sec [59-79]; p = 0.69, respectively) and MCF (65 mm [62-68] vs 66mm [63-68]; p = 0.95, respectively). Considering the vWF/ADAMTS13 ratio, recently proposed to be altered in endometriosis, no difference was seen between affected and no-affected women (0.95 [0.76-1.14] vs 0.91 [0.68-1.15]; p = 0.41, respectively). Finally, all the basic coagulation parameters were also similar between groups. Limitations, reasons for caution Our sample size does not allow us to perform sub-analyses regarding the type of endometriosis, although we cannot exclude differences according to the various manifestations of the disease. Also, not having a systemic haemostasis imbalance does not exclude the possibility of local coagulation imbalances. Wider implications of the findings An altered systemic haemostasis could be worsened by the use of hormonal treatments. Our result indicating that there is no coagulation imbalance at a systemic level reassures about the absence of further contraindications to hormonal drugs as a treatment for endometriosis. Trial registration number not applicable

Community Pharmacists Identification of Gaps in Care - Statin Utilization for Primary Prevention.

Background: Statins are a highly effective lipid-lowering therapy associated with significant reductions in atherosclerotic cardiovascular disease (ASCVD) events and death. Despite these benefits, statins are underutilized. Pharmacist-led interventions to increase statin prescribing are effective. To our knowledge, no prior studies implemented a comprehensive cardiovascular risk assessment utilizing point-of-care (POC) testing in community pharmacies. Objectives: The primary objective was to determine if community pharmacists can be utilized to identify gaps in care regarding appropriate use of statin therapy for prevention of ASCVD events in HPSAs. Secondary objectives were to assess public interest in ASCVD risk assessment and statin prescribing by the pharmacist, and to identify factors associated with statin gaps in care. Methods: A cross-sectional study was conducted at three independent community pharmacies. Participants were identified based on age and medication history and were scheduled at their pharmacy to receive a comprehensive ASCVD risk screening consisting of POC measurement of a complete lipid panel, blood glucose or A1C, and blood pressure. Participants were informed of their statin candidacy at the screening. Participants completed a survey regarding perceptions of the services provided and opinions of statin prescribing by pharmacists. Results: Of the 57 participants, 43 (75.4%) were possible statin candidates. Most indicated trusting their pharmacist to prescribe a cholesterol-lowering medication and felt insurance should pay for these screenings. Conclusion: ASCVD risk assessment conducted within the community pharmacy setting for can be utilized to identify treatment gaps in status use. Participants indicated trusting pharmacists to provide this service and found the service valuable.

Discrepancies between two total IgE assays and difference in reference intervals in healthy adults

ObjectiveTo compare total immunoglobulin (Ig) E assay performance characteristics between Abbott Architect and Siemens Immulite test systems. Reference intervals were also determined for both platforms in an American population of healthy adults. MethodsAgreement of the two total IgE assays was evaluated in a cohort of 331 subjects with normal complete blood count (CBC) and comprehensive metabolic panel (CMP) results. Reference intervals were established in 302 subjects after exclusion of atopic individuals on the Abbott Architect and Siemens Immulite test systems. ResultsWe demonstrated a 32% positive bias for total IgE quantitation on the Siemens Immulite platform compared to the Abbott Architect, despite both methods calibrated against the same WHO international reference material (75/502), Furthermore, the upper limit of the reference interval (95th percentile) was determined to be higher for the Siemens Immulite assay compared to the Abbott Architect (132 and 102 IU/mL, respectively). ConclusionDespite the use of a common WHO reference material for total IgE assay calibration, significant differences in quantitation was observed between two FDA-cleared test systems. Given that, it is warranted for clinical laboratories to verify vendor established reference intervals and adjust accordingly based on internal assessment of the normal range.

Malic enzyme 1 knockout has no deleterious phenotype and is favored in the male germline under standard laboratory conditions.

Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1. Herein, we describe two new genetically engineered mouse models exhibiting ME1 loss at dynamic timepoints. Using murine embryonic stem cells and Flp/FRT and Cre/loxP class switch recombination, we established a germline Me1 knockout model (Me1 KO) and an inducible conditional knockout model (Me1 cKO), activated upon tamoxifen treatment in adulthood. Collectively, neither the Me1 KO nor Me1 cKO models exhibited deleterious phenotype under standard laboratory conditions. Knockout of ME1 was validated by immunohistochemistry and genotype confirmed by PCR. Transmission patterns favor Me1 loss in Me1 KO mice when maternally transmitted to male progeny. Hematological examination of these models through complete blood count and serum chemistry panels revealed no discrepancy with their wild-type counterparts. Orthotopic pancreatic tumors in Me1 cKO mice grow similarly to Me1 expressing mice. Similarly, no behavioral phenotype was observed in Me1 cKO mice when aged for 52 weeks. Histological analysis of several tissues revealed no pathological phenotype. These models provide a more modern approach to ME1 knockout in vivo while opening the door for further study into the role of ME1 loss under more biologically relevant, stressful conditions.