Blood Draw Research Articles

Serum metabolomics improve risk stratification for incident heart failure

Abstract Background The prediction and early detection of heart failure (HF) is vital to reduce its substantial impact on quality of life, survival and healthcare expenditure. Current incident HF risk stratification strategies achieve only modest performance. Moreover, state-of-the-art risk scores focus on commonly acknowledged clinical risk factors, thus necessitating the integration of heterogenous data sources and prioritizing individuals with obvious risk constellations. Purpose Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF. Methods Leveraging data of n = 68,311 individuals and > 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort, we (I) evaluated the association of individual metabolites with incident HF via fitting of per-metabolite COX proportional hazards models and (II) trained and validated elastic net (EN) models to predict incident HF using the serum metabolome. Discriminative performance was benchmarked against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF). External validation was conducted in the independent FINRISK study. Results Several metabolites were independently associated with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755, ΔC = 0.013 (95% confidence interval (CI) 0.004 – 0.022), continuous net reclassification improvement (NRI) = 0.287 (95% CI 0.200 – 0.367), relative integrated discrimination improvement (IDI): 17.47 % (95% CI 9.463 - 27.825)). Simplified models only including age, sex and metabolomics performed almost as well as the PCP-HF model (Harrel’s C: 0.745 vs. 0.755, ΔC = 0.010 (95% CI -0.004 - 0.027), continuous NRI: 0.097 (95% CI -0.025 - 0.217), relative IDI: 13.445 % (95% CI -10.608 - 41.454)). Risk and survival stratification was improved by integrating metabolomics. External validation within FINRISK revealed similar patterns using the original model coefficients. Conclusions Serum metabolomics improve the prediction of incident HF risk. Scores obtained from the combination of age, sex and metabolomics exhibit similar predictive power as clinical risk models. Offering serum metabolomics to a middle-aged cohort might significantly improve HF risk stratification, thus facilitating preventive efforts. Via a single blood draw, serum metabolomics displays a highly cost- and time-effective, standardizable, and scalable alternative to clinical risk scores involving physical measurements and history taking in addition to clinical chemistry.Relative performance (test split)ROC & DCA plots (test split)

C-reactive protein improves the ability to detect hypertension and insulin resistance in mild-to-moderate obstructive sleep apnea: Age effect.

C-reactive protein (CRP) appears to improve the ability to detect cardiometabolic risk in young and middle-aged adults with mild-to-moderate obstructive sleep apnea (mmOSA). The aim of this study is to assess utility of CRP in identifying the risk of hypertension and insulin resistance across a wide age range including older patients with mmOSA. Adults (n = 216) of a wide age range (28-90 years old, mean age 52.64 ± 12.74) with mmOSA (5 ≤ AHI < 30) completed in-lab polysomnography or home sleep apnea testing, physical examination including blood pressure (BP) measures, structured medical history questionnaire, and blood draw for CRP and fasting glucose and insulin levels. In adults < 60 years, lnCRP but not the apnea-hypopnea index (AHI) was associated with greater odds for hypertension (odds ratio [OR] = 2.40, 95% CI = 1.20-4.84, p = 0.01; OR = 1.00, 95% CI = 0.92-1.08, p = 0.92, respectively) and with higher average systolic and diastolic BP. Also, in adults < 60 years lnCRP but not AHI, was associated with higher lnHOMA values. In contrast, in adults > 60 years neither lnCRP nor AHI were associated with greater odds for hypertension, average systolic and diastolic BP, and lnHOMA. Receiver-operating characteristics curves revealed that adding CRP to standard clinical factors (age, sex, and BMI) yielded moderately good risk models for hypertension in patients < 60 years (AUC = 0.721). In conclusion, CRP improves the ability to detect cardiometabolic risk in young and middle-aged, but not older adults with mmOSA, suggesting that inflammation may be a primary pathogenetic mechanism in younger patients with OSA.

Evidence-based recommendations regarding risk reduction practices for people at risk of or with breast cancer-related lymphedema: consensus from an expert panel.

Several recent studies have investigated the validity of precautionary practices for lymphedema risk reduction after breast cancer treatment, such as avoidance of blood pressure measurements, skin puncture, blood draws, and use of prophylactic compression during air travel. Other studies have elucidated risk factors for breast cancer-related lymphedema, such as axillary lymph node dissection and skin infection (cellulitis). Combining the current evidence base with the consensus opinion of lymphatic experts assembled at the American Cancer Society/Lymphology Association of North America Summit in October 2023, updated evidence-based risk reduction recommendations are presented for those with or at risk of breast cancer-related lymphedema. Recommendation topics include prospective surveillance, patient education, individual risk factors, exercise, blood pressure, skin care and hygiene, skin puncture and blood draws, surgical procedures, prophylactic compression, air travel, and hot climate and sauna. These recommendations will help inform education and medical choices for individuals treated for breast cancer who are at risk of or diagnosed with breast cancer-related lymphedema. More high-quality evidence is required to allow the development of risk reduction recommendations for other cancer types such as gynecological, melanoma, and head and neck. It is recommended that clinicians and organizations serving people at risk of or with lymphedema align risk reduction guidelines with the evidence-based recommendations provided within this consensus document and companion manuscripts from the American Cancer Society/Lymphology Association of North America Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management.

54 Efficacy of a quality improvement project in paediatric procedural pain management during needle procedures

Abstract Background In paediatric hospital settings, needle procedures significantly contribute to children’s experiences of pain and distress. A structured approach integrating preparation, comfort positions, distraction, relaxation techniques, and topical anesthetics can enhance children’s ability to cope with procedural discomfort. We developed a quality improvement (QI) initiative aiming to alleviate procedural pain and distress through a staggered implementation approach over a 3-year period. Objectives This study aimed to evaluate the impact of the first 2 years of an institutional QI initiative on managing procedural pain and distress in children undergoing needle procedures. The primary objective was to evaluate the use of multimodal strategies to reduce needle-related procedural pain/distress following the QI initiative. The secondary objective was to compare pain scores for needle procedures before and after the QI initiative. Design/Methods This observational study was conducted in a tertiary care university-affiliated paediatric hospital with an ongoing hospital-wide QI initiative aiming to alleviate procedural pain and distress in children undergoing needle procedures. The QI initiative consisted of mandatory sector-by-sector training of healthcare providers (HCP) on procedural pain/distress strategies to increase the use of multimodal pain care. Pain scores were measured during needle procedures (i.e. Numerical Rating Scale (NRS), Faces Pain Scale-R (FPS-R) or the FLACC scales, according to patient age) pre and 3-6 months post implementation of the QI initiative. Scheduled audits were conducted using a standardized questionnaire by a deployment champion nurse during needle procedures to document pain scales and pain/distress strategies used by the HCP during needle procedures in each of the hospital services. Results Throughout the first two implementation years (June 2021-June 2023), 363 audits were conducted on needle procedures for 363 children (Median age 7 yo (0month-18yo□). At this stage, audits took place in 14 different hospital services. The most frequent procedures were IV-line insertions (34%), venous blood draws (27%), and capillary blood sampling (26%). Parental presence and the use of distraction techniques were frequently used (90% and 80% of procedures, respectively). Of the 363 audits, 221 were pre-implementation and 142 post-implementation. Post QI initiative, an increased number of procedures were realized using multimodal strategies (4 or more strategies) to reduce pain/distress (from 60% to 78%). Pain scores were recorded for 203/221 audits pre and 134/142 post with a reduction in severe pain scores (7 or more) from 25% pre to 5% post-implementation. Conclusion The institutional QI initiative demonstrated both an increase in the number of strategies used to prevent pain/distress and a reduction in severe pain scores associated with paediatric needle procedures. This project emphasizes the significance of employing a multifaceted approach to managing procedural pain/distress in children undergoing needle procedures.

Low psychological resilience and physical fitness predict attrition from US Marine Corps Officer Candidate School training

ABSTRACT The objective is to examine the predictors of attrition in male and female candidates undergoing a 10-week early career military training program. 1006 candidates (79.5% male, 24.7 ± 3.2 years) consented to participating in a larger study examining predictors of injury during US Marine Corps Officer Candidates School (OCS). Participants completed a blood draw, demographic and psychological characteristics questionnaires, and two fitness tests. Participants were then grouped based on successful completion of OCS or not. Associations between potential predictors and attrition were analyzed using simple logistic regression analyses, followed by a backward stepwise elimination method. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to determine the accuracy of the attrition prediction model. 260 candidates (25.8%) attritted over the 10-week training, with the highest number of discharges during week 5. Musculoskeletal injury (MSKI) was the most common cause of attrition (30%), followed by non-MSKI medical (21.5%), and volitional withdrawals (19.6%). Sex, body mass index (BMI), resilience, initial physical fitness test score, combat fitness test (CFT) score, and prior military service were all significantly associated with attrition from OCS (all p < .05). The final prediction model of attrition included CFT score (p = .027) and resilience (p = .018). Multiple demographic, psychological, and fitness characteristics are associated with attrition from an early career military training course (OCS) and may be utilized as part of early screening procedures to identify and provide guidance for individuals at risk for not completing OCS.

Rare Case of Subcutaneous Phaeohyphomycosis Caused by Exophiala jeanselmei

Abstract Introduction/Objective Phaeohyphomycosis is a neglected tropical infection caused by dematiaceous fungi containing melanin in their cell wall. Currently, the prevalence of phaeohyphomycosis is very low in the United States compared to other mycotic agents. Trauma often precedes phaeohyphomycosis, and there are a limited number of cases associated with healthcare settings. This case report describes a nosocomial phaeohyphomycosis caused by Exophiala jeanselmei. Methods/Case Report A 60-year-old male with multiple myeloma, on immunosuppressive therapy, presented with a large fluctuant mass on the dorsum of his right hand. The mass had developed 6 months ago as a hematoma following a blown vein during a blood draw. Despite treatment with antibiotics, the mass continued to grow. The patient underwent surgical excision of the lesion, and the purulent aspirate was sent to the microbiology lab. Aerobic, anaerobic, mycobacterial, and fungal cultures, along with Gram and AFB stains, were performed. Direct microscopy of the aspirate revealed numerous leukocytes and few yeast cells. No sclerotic bodies were observed. Fungal growth with black pigmentation was observed during the second week of incubation. Colonies initially appeared smooth black and mucoid, later transforming into raised dome-shaped structures with a suede-like texture. Microscopic analysis revealed budding yeast cells and subglobose to broadly ellipsoidal germinating cells, which developed into short torulose hyphae before gradually transforming into unswollen hyphae. The isolate was further identified through D2 rDNA sequencing, revealing a 100% match for Exophiala jeanselmei. The patient was prescribed a one-month course of itraconazole treatment. The patient is progressing well during follow-up. Results (if a Case Study enter NA) NA Conclusion This case emphasizes the need for heightened clinical awareness in diagnosing phaeohyphomycosis, particularly in healthcare environments. Unique traumatic events like venepuncture should raise suspicion of phaeohyphomycosis. Culture and molecular diagnostics play a crucial role in confirming fungal causes and guiding treatment, leading to better patient outcomes.

7497 Association between Plasma Prolactin Levels and Menopausal Vasomotor Symptoms

Abstract Disclosure: F. Galbiati: None. J. Kang: None. D.J. Cote: None. J.E. Manson: None. U.B. Kaiser: None. Background: High prolactin (PRL) levels inhibit gonadotropin-releasing hormone (GnRH), causing hypogonadism. GnRH release is regulated by neurokinin B (NKB) and kisspeptin. NKB antagonists are used in treatment of menopausal hot flashes and vasomotor symptoms (VMS). In mice and humans with hyperprolactinemic anovulation, kisspeptin restored ovarian cyclicity and LH pulsatility. However, the interplay between kisspeptin and PRL is not fully understood. In two menopausal women with hyperprolactinemia and central hypogonadism, treatment with bromocriptine led to PRL normalization and new-onset VMS, suggesting that hyperprolactinemia inhibited VMS associated with hypogonadism. We aimed to investigate the association between PRL and menopausal VMS in women from the Nurses’ Health Study I and II (NHS, NHSII). We hypothesized that women with higher PRL levels would have a lower frequency/severity of menopausal VMS. Methods: We conducted a cohort study of 2618 females enrolled in NHS (n=1692) and NHSII (n=926) in whom blood samples were collected between 1989-99, were not pregnant or on hormonal therapy, and were either pre or post-menopausal as of blood draw. Subjects were free of breast, ovarian and other cancers, and provided complete data on VMS at menopause as well as in the past 4 weeks (assessed in 2008 in NHS and 2009, 2013, 2017 in NHSII). Plasma PRL was measured as part of 28 case-control studies of various health outcomes. We evaluated the presence and severity of VMS at menopause and 4 weeks prior to the questionnaire, as well as duration (in years) of VMS. We used multiple logistic regression, adjusting for covariates to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). Results: Women were aged 33-65 years at blood draw; range for years from blood draw to menopause was -10 to 10 (median=1.8) years; range for years from blood draw to report of VMS (both at menopause and current VMS) was 9.8 to 22 years. Mean PRL (SD; range) was 14.7ng/mL (10.1; 0.08-246). Women with the highest PRL levels were likely to be younger and less likely to be current smokers or obese. 77.4% of women reported VMS at menopause and 47.6% in recent 4 weeks; 52.3% reported moderate-to-severe VMS at menopause and 32.0% reported VMS in recent 4 weeks. Overall, PRL was not associated with duration of VMS or moderate-to-severe VMS at menopause or in the past 4 weeks; compared to the lowest quintile (≤8.0ng/mL), those in the highest PRL quintile (≥18.2ng/mL) had MVRR of 1.23(95%CI=0.94,1.60) for moderate-to-severe menopausal VMS and 1.03(95%CI=0.67,1.59) for recent VMS. Menopausal status did not affect the association between prolactin levels and VMS. Conclusion: PRL levels were not associated with occurrence, severity, or duration of menopausal VMS in a large cohort of women. Presentation: 6/1/2024

7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon

Abstract Disclosure: J. Fedorko: None. P. Subarajan: None. A.P. Amblee: None. C.A. Poku: None. Background: The term ‘pseudohypoglycemia’ is used to describe the disparity between actual and measured capillary glucose and clinical presentation. It has been used to describe situations when a patient has the characteristic symptoms of low blood glucose (BG) Whipple’s triad), but the patient’s BG levels are within normal limits. Alternatively, this term can also be used to describe falsely low BG levels on finger-stick (capillary) readings in a patient with normal serum glucose levels and without the characteristic Whipple’s triad. Case: A 55-year-old female with Raynaud’s phenomenon was seen in Endocrine clinic with persistent hypoglycemia noted on finger-stick glucose readings. Her finger-stick glucose reading was 43, and was subsequently given 24 grams of glucose gel. Ten minutes later, a repeat finger stick BG was 44. She had no weakness, tremors, shakiness, vision changes, confusion, seizures, lightheadedness, dizziness, tachycardia, palpitations, nervousness, hunger, paresthesias irritability, confusion, seizures, loss of consciousness, or any other symptoms or signs of hypoglycemia. She had no such previous episodes and her fasting BG ranged from mid-70s to 80, with post-meal BG ranging from 100 to mid-100’s. Her most recent hemoglobin A1c was 5.5. She regularly experiences cyanosis of fingers consistent with Raynaud’s phenomenon, triggered by cold air in winter and air conditioners in summer. She does not take any medications for these episodes. Given the absence of classic Whipple triad and normal BG from peripheral blood draw, the patient’s low finger stick BG readings were attributable to Raynaud’s phenomenon. It is postulated to be secondary to decreased perfusion in the digital microcirculation and increased blood transit time in the fingers, resulting in a local increase in glucose consumption and thus low capillary finger stick BG levels. Simultaneously done serum glucose levels are usually normal. Conclusion: Pseudohypoglycemia can occur in patients with impaired peripheral circulation such as Raynaud’s phenomenon, acrocyanosis, peripheral vascular disease, shock, or with increased glycolysis by blood cells like in leukemia, polycythemia and rare infections like African trypanosomiasis, hyperviscosity syndromes like Waldenstrom’s and monoclonal gammopathy of undetermined significance. In patients with low finger-stick (capillary) glucose levels who do not display Whipple’s triad, and have comorbid conditions that might interfere with the BG reading, it is important for clinicians to recognize the difference between true and pseudohypoglycemia. This can be confirmed with a simultaneously done normal serum glucose level and will prevent unnecessary investigations or excessive treatment. Presentation: 6/3/2024

12509 Identification Of Novel Exercise Training-induced Circulating Proteins: Hemostatic, Apoptotic, And Key Neuronal Factors

Abstract Disclosure: A. Shalit: None. M. Vamvini: None. P. Nigro: None. L.K. Simpson: None. H. Pan: None. J.M. Dreyfuss: None. L.J. Goodyear: Grant Recipient; Self; Daiichi Sankyo. R.J. Middelbeek: None. Exercise training induces a plethora of health benefits including improved glucose homeostasis, decreased cardiovascular disease, and improved cognitive function. An emerging concept is that many of these beneficial effects of exercise are mediated through the secretion of humoral factors into the blood. Identification of these exercise-regulated factors hold promise for novel treatments for disease. Here, we performed proteomic analysis to discover novel circulating factors in response to endurance exercise training in human participants. Given that nutritional status can affect the circulating proteome, another aim was to determine if proteomic adaptations to exercise training have similar effects under both fasted and random-fed conditions. Sedentary normoglycemic participants (3M/5F, age 22-41y) performed a supervised 10-week exercise training program, which by week 4 was 4x60 min exercise at 65-70% V̇O2peak. Fasted and random-sampling morning blood draws were collected pre-training and between 24-72 hours following the final training session. Proteomic detection was by SOMAscan. Exercise training significantly improved V̇O2peak by 17% (p=0.003). Out of 1,310 detected proteins, exercise training significantly changed 293 proteins in the fasted state and 360 proteins in the random-sampling state (p&amp;lt;0.05). Integration showed that 172 proteins were changed under both nutritional conditions (123 upregulated and 49 downregulated). Gene Set Enrichment Analysis (GSEA) of the commonly upregulated proteins showed that training resulted in enrichment in neuronal, hemostatic, and apoptotic pathways, whereas the downregulated proteins were enriched in neuronal and extracellular matrix processes. Since neuronal pathways were identified in both up and downregulated proteins, we focused our analysis there, identifying 31 upregulated and 4 downregulated neuronally-associated proteins. Importantly, exercise training reduced levels of CDK5, a protein that is hyperactivated in neurodegeneration and Alzheimer's disease. Moreover, GSTP1, a direct inhibitor of CDK5, along with downstream proteins inhibited by CDK5 (RAC1, STUB1, 14-3-3ε/YWHAE, HSP90AA1, CFL1), were significantly increased following exercise training.In conclusion, exercise training regulates circulating factors involved in neuronal, hemostatic, apoptotic, and extracellular matrix pathways, with these effects being independent of nutritional status. Our finding of exercise training-induced decreases in multiple proteins of the CDK5 pathway, a pathway whose downregulation is associated with neuroprotection, identify CDK5 as a novel and potentially important mediator of the beneficial effects of exercise training on cognitive function. Presentation: 6/1/2024

12581 Association Between AMH And Psychological Symptoms Across The BMI Spectrum In Peri-menarcheal Adolescents: Preliminary Findings

Abstract Disclosure: H. Vanden Brink: None. K.C. McCormick: None. M.E. Lujan: None. J. Chang: None. L. Ipp: None. A. Alladeen: None. J. Mendle: None. Introduction: Depression, anxiety, and disordered eating are associated with Polycystic Ovary Syndrome in adults and adolescents with PCOS, and significantly impact quality of life as well as intervention and PCOS management success. Elevated AMH and obesity are known risk factors for future PCOS risk. Thus, the objective was to determine whether AMH was associated with the degree of psychological symptoms in the peri-menarcheal years across the adiposity spectrum. Methods: 40 females (n=12 pre-menarcheal, n=28 &amp;lt;2 years post-menarche) underwent a non-fasting blood draw, anthropometry, menstrual history, and a series of surveys to evaluate depression (CES-DC), anxiety (MASC), perceptions of pubertal-related change (POPS), and transdiagnostic psychological processes (rumination, emotional clarity) which can contribute to, and are risk factors for, psychopathology. Anti-mullerian hormone was measured using picoAMH assay (Motive Biosciences Inc). Linear regression analyses were conducted to determine whether AMH, body habitus (lean [n=26], overweight [n=7], obesity [n=7]) were associated with psychological symptoms. A BMI category-by-AMH interaction was included to test the hypothesis that relationship between psychological symptoms and AMH was greater among those living with obesity, who are at an increased risk of progression to PCOS. Results: In the full model, depression scores were positively associated with AMH (p=0.035), and an AMH*BMIcat interaction was trending (p=0.059), such that the association between AMH and depression scores among those with obesity was greater (p=0.026). POPS was positively associated with AMH, only after inclusion of BMI (p=0.029). Lower body appreciation scores and a higher drive for thinness were associated with higher AMH only among those with obesity (BAS: interaction term p=0.087; parameter estimate AMH*OB p=0.045; EDI: interaction term: 0.061, AMH*OB parameter estimate, p=0.019). Rumination and anxiety also demonstrated a BMI-dependent association with AMH; both were positively associated with AMH among participants with obesity (rumination, interaction p=0.014, AMH*OB parameter estimate p=0.007; anxiety interaction p=0.0009, AMH*OB parameter estimate p=0.0002), but the inverse was detected in lean participants (rumination AMH*Lean parameter estimate p=0.014; anxiety AMH*Lean parameter estimate p=0.009). Conclusion: While preliminary, these findings suggest that obesity and elevated AMH in the pre- and early post-menarcheal years is associated with increased symptoms that could affect psychological well-being symptoms. Research is ongoing to validate these findings in a larger, more diverse cohort and to assess subsequent PCOS risk. Presentation: 6/3/2024

7874 Management Of “Hyperandrogenism” Confounded By Dermatology Biotin Prescriptions

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S. Sathyanarayana: None. C. Siddlingappa: None. K. M: None. T.-. Kamala: None. R.B. V: None. V. Nath: None. M.D. Chitra: None. P. Ravikumar: None. Introduction: Immunoassay interferences include: Cross-reactions, heterophile antibodies, biotin and anti-analyte antibodies, with positive or negative bias, leading to difficulties in clinical decision-making (confounding diagnosis, unnecessary investigations or inappropriate treatments). The interfering substance may be exogenous (e.g., drug or substance absorbed by patient) or endogenous (e.g., antibodies produced by patient). Clinical Case 2023 Dec 1 Dermatology management for hyperandrogenism 28-year-old female evaluated for acne 3 years (increased 4 months), hair fall 6 months and hirsutism 3 years (threading) Total Testosterone 443 ng/dL (10-55) CLIA Free Testosterone 8.9 pg/mL (0.1-6.4) ELISA DHEAS 209 µg/dL (35-430) CLIA S Cortisol 8 am 6.9 µg/dL (2.6-10.5) CLIA LH 4.2 mIU/mL (1.9-12.5); FSH 5.3 mIU/mL (3.0-8.0) T3 133 ng/dL (80-200); T4 8.5 ug/dL (4.8-12.7), TSH 3.78 µIU/mL (0.5-5.3) HbA1c 5.0%; Glucose fasting 81 mg/dL; Insulin fasting 39.4 mU/L (3-25); HOMA-IR 5.2; HOMA%B 380; HOMA%S 19.2; T3 133 ng/dL (80-200) 2023 Dec 14 Endocrinology for “scaringly” very high testosterone levels Menstrual history: Menarche 11 years; Cycles regular. Unmarried Family history: Diabetes++; Hirsutism+; Infertility- Physical exam: Height 159 cm; Weight 55 kg; BMI 21.8 kg/m2; Ferriman Gallwey score 11; Pulse 75; BP 79/62; Thyroid: Grade 0. In view of total testosterone levels in “neoplastic androgen excess” range, further endocrinology evaluations (multiple labs and assays) were carried out. However, discordance between the mild clinical versus severe biochemical hyperandrogenism was noted. Review of the dermatology prescription indicated that patient had consumed only one 10 mg tablet of biotin 36 hours before the earlier blood draw obtained by dermatologist. Total Testosterone 22.3 and 33.8 ng/dL (6-82) ECLIA; 19.7 (15-70) LCMS Free Testosterone 0.69 pg/mL (&amp;lt; 2.85) (ELISA) DHEAS 101 µg/dL (45-380) LCMS Androstenedione 104 ng/dL (75-205) LCMS 17OH Progesterone 0.89 ng/mL (0.16-2.05) EIA; 0.40 (0.35-2.9) LCMS S Cortisol 5.92 ug/dl (6-18) ECLIA; 5.45 (5-23) LCMS FSH 2.74; LH 6.07; Prolactin 20.1 ng/mL (4.7-23.3) T3 114 ng/dL; T4 7.2 µg/dL; TSH 1.29 Diagnosis Falsely elevated total testosterone (and free testosterone) levels due to biotin immunoassay interference. Clinical Lessons: Very limited studies exist confirming the exact clinical indications for biotin (eg: improvement of hair quality or quantity, or nail growth). FDA warning highlights biotin’s interference (false elevations or reductions) with immunoassays relying on biotin-streptavidin technology. Physicians must ask patients about supplement usage, and discontinue biotin for 8 hours for patients taking 10 mg/day, 3 days for 100-300 mg/day, 7 days for children taking 2 and 15 mg/kg/daily, and inform laboratory if diagnostic test was performed while taking biotin. Presentation: 6/2/2024

12559 Objective Versus Subjective Measures Of Reproductive Development And Psychological Well-Being In Peri-Menarcheal Adolescents: A Pilot Study

Abstract Disclosure: K.C. McCormick: None. M.E. Lujan: None. J. Chang: None. L. Ipp: None. A. Alladeen: None. H. Lamar: None. J. Mendle: None. H. Vanden Brink: None. Introduction: Risk of psychopathology emerges during the pubertal and peri-menarcheal years; however objective physiological measures of maturation often differ from adolescents’ own reports of their development. Understanding how psychological symptoms emerge in relation to both objective and subjective evaluations of reproductive development can provide critical insights into mental health risk and variability in psychological symptom severity during the pre-menarcheal and early post-menarcheal years. Methods: 52 females 9-15 years old (n=16 pre-menarcheal, n=36 &amp;lt;2 years post-menarche) underwent a non-fasting blood draw for reproductive hormones (estradiol, anti-mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH)), anthropometry, detailed reproductive and menstrual history, and a series of surveys to evaluate depression (CES-DC), anxiety (MASC), perceptions of pubertal-related change (POPS), and transdiagnostic psychological processes (rumination, emotional clarity) which can contribute to, and are risk factors for, psychopathology. Whether psychological symptoms are associated with objective measures (menarche, gynecological age, reproductive hormone concentrations) versus subjective measures (self-reported tanner stage, severity of dysmenorrhea) were contrasted using t-tests and Pearson Correlation Coefficient analyses (JMP Pro (v17)). Results: The majority of participants (26/36 post-menarcheal and 11/16 pre-menarcheal) exceeded the standard cut-off of 15 for depressive symptoms, consistent with research on mental health symptomatology in this cohort of youth. POPS scores were higher (39±10.9) in post-menarcheal versus pre-menarcheal (31±12.6) adolescents indicating post-menarcheal adolescents reported more puberty-linked change in their lives (Pttest=0.04). Lower emotional clarity was associated with higher AMH concentrations (r= -0.27, p=0.0944). Depressive symptoms tended to be greater (27+14.8) in those with moderate dysmenorrhea versus mild/no dysmenorrhea (19±11.1, Pttest=0.08). Depression (r=0.30, p=0.032) and anxiety symptoms (r=0.32, p=0.027), and rumination (r=0.30, p=0.033) were associated with higher self-reported Tanner scores; POPS was trending (r=0.25, p=0.0776). Neither estradiol nor FSH were associated with any measures of psychological well-being. Conclusion: Both objective measures of reproductive development and adolescent self-reports may help providers assess individual vulnerability to internalizing psychopathology, such as depression and anxiety. Additionally, given population level increases in depressive symptoms in adolescents, researchers should avoid utilizing simple cutoffs for depression and anxiety, which lack specificity and overlook critical variability which can further elucidate mental and physical health dynamics. Presentation: 6/2/2024

12669 Oxytocin Levels Are Associated With Inhibitory Control In Young Female Individuals With A Low-weight Eating Disorder

Abstract Disclosure: M. Wronski: None. F. Plessow: None. M. Rogers: None. D.L. Kahn: None. E.R. Golden: None. M. Slattery: None. J.J. Thomas: None. L.M. Holsen: None. K.T. Eddy: None. M. Misra: None. E.A. Lawson: None. Background: Preclinical and clinical evidence suggests that the hypothalamic neuropeptide oxytocin (OXT) impacts inhibitory control and reward processing. In male adults with overweight or obesity, we showed that exogeneous OXT increases inhibitory control and neural activation in associated brain regions while attenuating activation in reward-related brain regions. Low-weight eating disorders (LWEDs) are characterized by decreased endogenous OXT levels, altered inhibitory control over behavior, and reduced responsiveness to rewards. However, links between these characteristics are unknown in LWEDs. Here, we examined associations between endogenous OXT levels and performance in behavioral tasks requiring inhibitory control and reward-based decision-making in individuals with a LWED compared to healthy controls (HC). Methods: In 58 females with a LWED and 39 female HC (aged 11-23 years), we measured serum OXT concentrations fasting and 30, 60, and 120 minutes after a 400-kcal standardized meal and calculated OXT area under the curve (AUC) as a composite measure. After the meal (following the 60-minute blood draw), participants completed a Go/NoGo Task to assess inhibitory control over behavior and a monetary Delay Discounting Task to assess reward-based decision-making. We analyzed associations between OXT AUC and behavioral outcomes across groups using robust linear models with main effects of group (LWED vs. HC) and OXT AUC, the interaction effect of group*OXT AUC, and covariates age and body mass index (BMI) z score. Results: Per study design, individuals with a LWED had a lower BMI z score (t=10.90, p&amp;lt;0.001, d=2.00), whereas groups did not differ in OXT AUC (t=1.20, p=0.232, d=0.24). For the Go/NoGo Task, we observed a group effect on NoGo error rate (higher values indicating lower inhibitory control; NoGo error rate: adj. mean [std. error] LWED 35.6 [2.7] % &amp;gt; HC 26.6 [3.4] %) as well as an interaction effect of group*OXT AUC, independent of age and BMI z score (t=2.73, p=0.008, d=0.72). Follow-up simple main effects analysis within each group revealed a significant negative relationship of OXT AUC and NoGo error rate in individuals with a LWED (t=-2.42, p=0.022, d=0.85), while this relationship emerged as nonsignificant but trend-level positive in HC (t=1.73, p=0.099, d=0.74). We did not detect group (t=0.69, p=0.493, d=0.17) or group*OXT interaction (t&amp;lt;0.01, p=0.996, d&amp;lt;0.01) effects on delay discounting rate. Conclusions: In females with a LWED, lower OXT exposure around a meal correlated with lower inhibitory control over behavior. In HC, however, our data yielded a trend of opposite directionality. Links between OXT exposure and reward-related decision-making were absent across groups. Our findings indicate potential relevance and mechanistic involvement of OXT in inhibitory control in LWEDs that warrants further causal investigations. Presentation: 6/3/2024

A near normal distribution of IQ in Fragile X Syndrome

Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of FMR1-protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning. A sample of 143 individuals with FXS (69% male), aged 8–50 years, completed IQ testing and blood draw via venipuncture to determine the relationship between Deviation IQ scores and FMRP levels as well as the distribution of Deviation IQ scores. In both males and females with FXS, higher FMRP levels were associated with higher Deviation IQ. However, this relationship was no longer significant when only examining full mutation, fully-methylated males. Yet, both the full and restricted male samples showed a downward shifted but otherwise normal distribution of Deviation IQ scores. Our findings support and extend previous studies establishing molecular markers of disease severity in FXS as well as provide novel evidence of a “FXS IQ standard curve”. This latter finding suggests inter-individual variation in Deviation IQ in FXS, especially among males, may be driven by similar factors known to impact cognitive outcomes in typically-developing individuals. Thus, future work aimed at understanding the mechanisms by which FMRP loss leads to intellectual disability should revisit the biological/genetic, socio-environmental, and epigenetic factors contributing to inter-individual variation in IQ in FXS.

B-349 Diagnostic Performance of the Atellica IM High-Sensitivity PSA Assay in Men Undergoing Prostate Cancer Screening

Abstract Background This study evaluated the diagnostic performance of the Atellica® IM High-Sensitivity PSA (hsPSA)* assay in men &amp;gt;50 years undergoing prostate cancer (PC) screening in conjunction with digital rectal exam (DRE). Methods Serum samples were collected prospectively from 2671 subjects &amp;gt;50 years referred to a urologist for evaluation of PC from 26 sites across the United States. To establish PC versus benign disease, all subjects underwent a transrectal prostate biopsy ≤60 days after blood draw. At the cutoff of 4.0 ng/mL for the hsPSA assay, the percentage of PCs detected (sensitivity) and corresponding percentage of biopsies avoided in men without PC (specificity) were determined. Results Cancer prevalence (malignant biopsy) was 58.5% (1562/2671) among the diagnostic population. Preliminary results demonstrated that for DRE alone, sensitivity and specificity were 30.9% (482/1562) and 83.0% (920/1109) compared to biopsy. For hsPSA alone at the cutoff of 4.0 ng/mL, sensitivity was 88.7% (1386/1562). The table provides incidence of cancer and positive biopsies by subgroups defined by DRE and hsPSA. hsPSA detected 61.1% (955/1562) of PCs that DRE did not. Of those DRE+, 71.8% (482/671) had positive biopsy. Of those DRE+ and hsPSA ≥4.0 ng/mL, 78.6% (431/548) had positive biopsy, which significantly increased PC detection by 7.0% (95% CI:1.4%-12.5%). Similarly, in the DRE- population, while 54.0% of subjects had positive biopsy, subjects both DRE- and hsPSA &amp;lt;4.0 ng/mL had only 38.5% positive biopsies, a significant difference of 16.5% (95% CI: 6.3%-27.8%). Conclusions Using DRE alone detected only 3 out of 10 patients with PC. It was observed that when used in conjunction with DRE, the hsPSA assay improved both sensitivity and specificity of PC detection over DRE alone. CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

Plasma proteomics and carotid intima-media thickness in the UK biobank cohort.

Ultrasound derived carotid intima-media thickness (cIMT) is valuable for cardiovascular risk stratification. We assessed the relative importance of traditional atherosclerosis risk factors and plasma proteins in predicting cIMT measured nearly a decade later. We examined 6,136 UK Biobank participants with 1,461 proteins profiled using the proximity extension assay applied to their baseline blood draw who subsequently underwent a cIMT measurement. We implemented linear regression, stepwise Akaike Information Criterion-based, and the least absolute shrinkage and selection operator (LASSO) models to identify potential proteomic as well as non-proteomic predictors. We evaluated our model performance using the proportion variance explained (R 2). The mean time from baseline assessment to cIMT measurement was 9.2 years. Age, blood pressure, and anthropometric related variables were the strongest predictors of cIMT with fat-free mass index of the truncal region being the strongest predictor among adiposity measurements. A LASSO model incorporating variables including age, assessment center, genetic risk factors, smoking, blood pressure, trunk fat-free mass index, apolipoprotein B, and Townsend deprivation index combined with 97 proteins achieved the highest R 2 (0.308, 95% C.I. 0.274, 0.341). In contrast, models built with proteins alone or non-proteomic variables alone explained a notably lower R 2 (0.261, 0.228-0.294 and 0.260, 0.226-0.293, respectively). Chromogranin b (CHGB), Cystatin-M/E (CST6), leptin (LEP), and prolargin (PRELP) were the proteins consistently selected across all models. Plasma proteins add to the clinical and genetic risk factors in predicting a cIMT measurement. Our findings implicate blood pressure and extracellular matrix-related proteins in cIMT pathophysiology.

A-348 Portable aptamer-based home monitoring system for blood phenylalanine measurement

Abstract Background Aptatek BioSciences, Inc. has developed a home monitoring tool for blood phenylalanine (phe) levels. The Aptatek system integrates a proprietary aptamer assay approach with a user-friendly handheld, smartphone-enabled test platform. PKU (phenylketonuria), is an inborn error of phenylalanine (Phe) metabolism If undiagnosed or untreated, phe accumulates in all body tissues, including the blood and brain, where it is especially neurotoxic and when untreated it can cause significant cognitive impairment and neurological defects. PKU management targets maintaining blood Phe concentration within the therapeutic range (120-360uM) to avoid severe neurological sequelae, mainly through nutritional therapy. Methods PheCheck™ includes a portable hand-held reader, software accessible as a mobile phone application, and a disposable single-use lateral flow cassette, blood collection, cap, and buffer chamber. PheCheck™ detects phe by binding of the phe in a small blood sample using small molecule-specific DNA aptamers. A patient (or caregiver) collects 5μl of capillary blood using a lancet to lance the fingertip and use the collection cap to collect the specimen. Once collected, the specimen is placed into the buffer chamber where the blood is diluted and processed in preparation for a lateral flow assay. The buffer chamber is placed on top of a lateral flow cassette to release the solution into the cassette. The lateral flow cassette is inserted into a small electronic reader after specimen incubation. The reader will detect a fluorescent signal from the strip and report the quantitative Phe concentration present in the specimen to the integrated mobile phone application. The reader has a simple design with a single operating push button, USB data connection port, and replaceable battery compartment. The reader reads the output of the lateral flow cassette and reports the result to a Smartphone app. The app is designed to either display the quantitative results or store the results without displaying the quantitative value. Results Twelve patients were trained on the PheCheck system and observed using the system for self-testing. Patients also prepared dried blood spot cards for comparative testing using LC-mass spectrometry. Patients were asked to return to the clinic within two weeks to retest. The blood phenylalanine levels measured by the PheCheck system were within targeted standard deviation of the dried blood spots demonstrating the feasibility of portable home-based testing for routine monitoring of blood phenylalanine levels in phenylketonuria patients. Such a portable system would enable real time monitoring and adjustment of diet or therapy for chronic diseases such as PKU. Conclusions Aptatek has developed a DNA aptamer based portable monitor for measuring blood phenylalanine levels. The system quantitatively measures phenylalanine from a 5-microliter finger stick blood sampler. Aptamer-based detection of phenylalanine provides reliable quantitation across a wide clinical concentration range and encouraging performance relative to gold standard testing of venous blood draw or dried blood spots. Analysis of samples from patients on Palynziq indicate that the PheCheck system could provide more reliable testing than venous blood draws. The system shows strong promise for routine home monitoring of blood phe levels by patients.

B-156 Extraction strategy for therapeutic drug monitoring of sirolimus and tacrolimus using volumetric absorptive microsampling

Abstract Background Following organ transplantation, patients are placed on immunosuppressant drugs (ISDs) to minimize the risk of rejection. Sirolimus and tacrolimus are two of the most widely used ISDs, however, due to their narrow therapeutic indices, patients require frequent therapeutic drug monitoring (TDM). Recurrent venipuncture can become uncomfortable and disruptive, especially in the pediatric population. Therefore, we describe an extraction method using dried whole blood from volumetric absorptive microsampling (VAMS) devices for the detection of sirolimus and tacrolimus by turbulent flow liquid chromatography tandem mass spectrometry (TFC-MS/MS). The use of VAMS in the clinical laboratory will provide ISD patients with a convenient alternative to traditional blood draws. Methods MassTrak immunosuppressant calibrators based on a whole blood matrix (Waters) were applied to 30 μL VAMS Mitra devices (Neoteryx) and dried overnight. To extract the whole blood off of VAMS tip, we tested various methanol:water solvent ratios, of which 30 μL was added to the device. Tips were extracted using ultrasonication (30 min), vortexing (5 min), and centrifugation. Once extracted from the tip, 25 mM zinc sulfate was added to whole blood extract at a 1:1 (v/v) ratio. An acetonitrile and methanol extraction reagent was then added to the whole blood/zinc sulfate solution at a 2:1 (v/v) ratio. After brief vortexing, samples were centrifuged at 16,060 × g (10 min) and tested using an established TFC-MS/MS method which deploys a TLX-2 system for sample preparation coupled to a Q-Trap tandem mass spectrometer (AB Sciex 5500). Results A 80:20 (v/v) water:methanol extraction solvent yielded the greatest extraction efficacy for both sirolimus and tacrolimus from the VAMS tips compared to other tested ratios. We established a 5-point calibration curve to correlate the measured values of ISDs with known MassTrak calibration standard concentrations. The resulting average calibration curve from 3 independent experiments was highly linear for both sirolimus (R2= 0.992; slope= 1.1; intercept= 0.94) and tacrolimus (R2= 0.996; slope= 1.1; intercept = 0.8819). Our VAMS whole blood extraction strategy was correlated to the established neat whole blood protocol, which utilized all of the sample preparation steps outlined above except the initial extraction from the VAMS tip. The average extraction efficacy was 89.1% for sirolimus with an average coefficient of variation (CV%) of 12.1% across 3 independent experiments. For tacrolimus, we demonstrated an average extraction efficacy of 100.1% with an average CV% of 8.4%, again across 3 independent experiments. Conclusions We demonstrate the feasibility of using a VAMS approach to TDM of sirolimus and tacrolimus. Our results demonstrate favorable recoveries for both of the tested drugs, evidenced by high recoveries of the external calibration standards. Additionally, our method exhibited high extraction efficacy and low variability. Further validation studies, including the utilization of clinical samples is necessary to confirm our preliminary findings.

A-019 Unexpectedly High Cardiac Troponin Values in Healthy Athletes after SARS-CoV-2 Infection

Abstract Background Elevated levels of cardiac troponin I or T (cTnI, cTnT) in general have immediate clinical consequences including invasive cardiac imaging and rhythm monitoring. Macro-troponin is a complex of antitroponin autoantibodies and cTnI or cTnT and may result in falsely elevated values. In athletes, a reliable exclusion of cardiac disease is crucial to allow for intensive exercise. The prevalence and causes of falsely elevated cTn in professional athletes after SARS-CoV-2 infection are unknown. Methods These are preliminary results of an observational study including 35 professional athletes (16 -75 years old, median 24 years; 19 females, 16 males) who had post-Covid-19 check-ups at their practicing sports physician mostly in the year 2022 (6 athletes in 2023). One female athlete did not have a proven SARS-CoV-2 infection but vaccination. Divergences in high sensitivity (hs) cTn concentrations were investigated according to the sex-specific cut-off values of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostics, Atellica/Siemens Healthineers, Access/Beckman Coulter and hs-cTnT: Cobas/Roche Diagnostics). All athletes were advised to stop training 48h before routine blood drawing and if required underwent electrocardiography (ECG), echocardiography and magnetic resonance imaging to exclude myocardial involvement, particularly when suspicious symptoms were present. Athletes with divergent hs-cTn assay results were further analyzed for the presence of macro-troponin using the reference method sucrose gradient ultracentrifugation. Results The two main professional sports were cycling (mountain biking or road biking) and soccer, further sports comprised curling, swimming, running including marathon, floorball, cross-country skiing or rhythmic gymnastics. Athletes mostly suffered from postviral exhaustion, mild infectious symptoms like headache, sore throat, dry cough, subfebrile temperature, or sniffles or had atypical thoracic pain. There were two males with known secondary diagnoses, one 25 years old with diabetes mellitus type 1 and one 75 years old with atherosclerosis and hypercholesterolemia. Eighteen (18/35) athletes had hs-cTn concentrations within the sex-specific cut-off values in all assays and did not undergo further investigation for macro-troponin by sucrose gradient ultracentrifugation. However, in 17 athletes (17/35) hs-cTn was increased in at least one assay method which was mostly a hs-cTnI method (for 2/17 all assays elevated). The sucrose-gradient ultracentrifugation method proved macro-troponin in 15/17 with original hs-cTn values for Abbott Alinity: 5 - 170 ng/L; Siemens Atellica: 9.6 - 376 ng/L; Beckman Access: 0.5 - 55 ng/L and Roche Cobas 4 - 77 ng/L. However, 2/17 had the free troponin form, one with only a minor hs-cTnT increase above the sex-specific cut-off and the other with increased values in all hs-cTn assays but normal values in a 2- and 4-days control follow-up measurement. Notably, there were no ECG or cardiac imaging findings including echocardiography or cardiac magnetic resonance imaging suggestive of myocarditis in the investigated athletes. Conclusions After SARS-CoV-2 infection, cTn might be increased in athletes without a correlate in ECG or imaging reports. This should prompt physicians to consider an assay interference by macro-troponin, particularly if a second troponin method such as hs-cTnT remains normal. AHL &amp; CK share first and OH &amp; CM share last authorship

Time toxicity of lutetium-177 treatment in gastroenteropancreatic neuroendocrine tumours

Objectives: We aim to investigate the time toxicity of patients with gastroenteropancreatic-neuroendocrine tumours treated with lutetium-177 Dotatate in a single institution. Design: This is a retrospective cohort study. Methods: All patients with gastroenteropancreatic-neuroendocrine tumours treated with lutetium-177 Dotatate in the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution. Results: Our cohort included 21 patients with metastatic disease, female sex 86%, and had a median age of 55 (IQR 44-63). The primary tumour site was small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was 2 (IQR 2 - 3). The overall response rate was 19%, and 66.6% had disease clinical benefit. The median calculated 'time toxicity' was 11 days (IQR 8-18), representing 5.7% of the total treatment duration. The main contributors to time-toxicity included infusion days, blood draws, radiological scans, and hospitalizations (median 4 days for each). Conclusion: Lutetium-177 Dotatate treatment for gastroenteropancreatic-neuroendocrine tumours was associated with a low time toxicity, excellent tolerability, good response and a prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survivals and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.