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Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology ( P  =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.A.H. is a co-founder and officer with equity interest of Lime Therapeutics Inc., co-founder with equity interest of Selectin Therapeutics Inc. and Resident Diagnostics, Inc., and a member of the scientific advisory boards of Concarlo Therapeutics Inc., Nanorobotics Inc., and Mediphage Bioceuticals Inc. B.W. reports research funding by Repare Therapeutics, outside of the submitted work. E.S. reports honoraria from Dilon Technologies, Inc. D.A.L. is a full-time employee of Merck & Co., Inc. (Rahway, NJ, USA) and a co-founder with equity interest of Resident Diagnostics, Inc. N.A.R. reports grant funding from GRAIL paid to the institution. D.S.C. reports personal fees from Apyx Medical, Verthermia Inc., Biom 'Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. K.L.R. reports travel support from Intuitive Surgical. T.Y.S and M.F. have no conflicts of interest to report., (© 2024 The Authors. Published by Elsevier Inc.)

Background: We evaluated the diagnostic utility of procalcitonin (PCT) in predicting bacterial bloodstream infections (BSI) in critically ill cancer patients with and without neutropenia. We also investigated the role of PCT as a prognostic marker of supportive modalities (vasopressors, invasive mechanical ventilation, and renal replacement therapy (RRT)) in the intensive care unit (ICU)., Methods: We retrospectively analyzed 2200 PCT and blood cultures from adult cancer patients with suspected sepsis. Primary outcome was BSI, defined by positive blood culture, collected within 72 h of PCT collection., Results: Median PCT values were higher in encounters with BSI (3.2 vs 0.5 ng/ml, p < 0.001). The area under the ROC curve (AUC) was 0.726 (95%CI 0.698, 0.754). PCT > 2.0 ng/ml was significantly associated with greater likelihood of BSI and this effect was significantly stronger for neutropenic (OR 9.09, 95%CI: 4.39, 18.79) compared with non-neutropenic patients (OR 4.00 (95% CI: 3.13, 5.10), interaction p = 0.036). PCT > 2.0 was associated with vasopressor requirement on ICU admission (OR 1.82 (95% CI 1.31, 2.53), p < 0.001) and RRT (OR 2.20 (95% CI 1.24, 3.91), p = 0.007)., Conclusions: Procalcitonin is a fair discriminator of BSI in critically ill cancer patients with and without neutropenia and a PCT > 2.0 ng/ml was significantly more likely to require vasopressors and RRT in the ICU., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Busulfan and melphalan are cytotoxic DNA alkylating agents that are used in many hematopoietic stem cell transplantation (HCT) conditioning regimens. We report the development of an assay using turbulent flow liquid chromatography (TFLC) and tandem mass spectrometry to simultaneously measure the concentration of busulfan (Bu) and melphalan (Mel) in human plasma. The method involves precipitating proteins in the plasma specimen with an organic solvent containing deuterated internal standards of both compounds. Following centrifugation, an aliquot of the supernatant was injected into the TFLC mass spectrometry system operated in the positive ion mode. The analytical measurement range for both compounds was 10-5000 ng/mL, and with validated dilutions the reportable range was extended to 25,000 ng/mL. Intra-day and inter-day (n = 20 day) precision studies showed a coefficient of variation (CV) of <7% at several concentrations across the measurement range. To determine accuracy recovery studies were performed at several concentrations spanning the measurement range. Recoveries for both compounds were between 98 and 103%. Additionally, busulfan was compared with an existing assay and showed excellent correlation. Experiments were conducted to rule out matrix effects, carryover and interference from endogenous substances. The validated clinically reportable range (CRR) and assay precision will allow this assay to be used clinically to monitor and adjust Mel and Bu levels to ensure better therapeutic outcomes and also to support clinical trials aimed at better defining therapeutic ranges., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Serum Chromogranin A (CgA) is widely used as a biomarker for pancreatic neuroendocrine tumors (PanNETs). The aim of this study was to investigate the value of CgA as a diagnostic and prognostic marker for well-differentiated PanNETs., Methods: Patients with well-differentiated PanNET and a baseline CgA measurement, between 2011 and 2016 were reviewed. The diagnostic value was determined by comparing CgA values from patients with PanNETs to those with other pancreatic neoplasms and healthy controls. The Kaplan-Meier method was used to investigate the CgA prognostic significance., Results: Ninety-nine patients met inclusion criteria. As a diagnostic marker, CgA had a sensitivity of 66%, specificity of 95%, and overall accuracy of 71%. The use of PPIs was associated with a higher CgA level (p = 0.015). When excluding patients on PPIs, CgA accuracy in distinguishing PanNETs from other pancreatic neoplasms was 66%, the sensitivity and specificity were 60% and 75% respectively. Elevated CgA (p = 0.004), Ki67% (p < 0.001), tumor grade (p < 0.001) and stage of disease (p = 0.036) were associated with disease-specific survival., Conclusion: CgA has a limited role as a diagnostic biomarker for well-differentiated PanNETs. An elevated CgA level may have prognostic value but its role should be further investigated with respect to other known pathological factors., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Very sensitive measurements of serum estrogens and testosterone are important in adult and pediatric endocrinology and immunoassays are known to lack the required performance at very low levels. Our aim was to develop a sensitive HPLC-MS/MS assay for both estradiol (E 2 ) and testosterone (Te) in serum without the need for chemical derivatization and using commercially available calibrators., Methods: Serum samples were prepared by the addition of internal standards followed by extraction using hexane:ethyl acetate. Chromatographic separation was achieved using a C 18 column and mass spectrometry was performed in both positive and negative ion modes., Results: The lower limits of quantitation (LLOQs) of E 2 and Te were 5pg/mL and 1ng/dL, respectively. The analytical measurement range (AMR) for E 2 was 5-600pg/mL and 1-1,170ng/dL for Te. Assay accuracy was determined both by comparison with a LC-MS/MS method performed at a national laboratory and the CDC HoSt program. Comparison with samples analyzed by both methods showed excellent correlation. Within-day (N=10) and between-day (N=20) CVs at concentrations spanning the AMR were less than 7% for both analytes., Conclusion: We have developed an accurate and highly sensitive assay to measure E 2 and Te levels in serum by HPLC-MS/MS without chemical derivatization and using commercially available calibrators., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A rapid and simple turbulent flow liquid chromatography (TFC-LC) method implementing positive heated electrospray ionization (HESI) for the accurate and precise determination of methotrexate (MTX), 7-hydroxy methotrexate (7-OH MTX), and 4-amino-4-deoxy-N(10)-methylpteroic acid (DAMPA) concentrations in serum was developed. MTX was isolated from serum samples (100μL) after protein precipitation with methanol containing formic acid and internal standard (MTX-D3) followed by centrifugation. The supernatant was injected into the turbulent flow liquid chromatography which is followed by electrospray positive ionization tandem mass spectrometry (TFC-LC-MS/MS) and quantified using a six-point calibration curve. For MTX and DAMPA the assays were linear from 10 to 1000nmol/L and for 7-OH MTX from 20 to 2000nmol/L. Dilutions of 10, 100 and 1000-fold were validated giving a clinically reportable range of 10nmol/L to 5×10(5)nmol/L. Within-day and between-day precisions at concentrations spanning the analytical measurement ranges were less than 10% for all three analytes. MTX, DAMPA and 7-OH MTX were sufficiently stable under all relevant analytical conditions. No significant matrix effect was observed during the method validation. The TFC-LC-MS/MS MTX method was also compared with three other clinically validated MTX assays: a dihydrofolate reductase (DHFR) inhibition assay, an immunoassay based on fluorescence polarization and a previously developed LC-MS/MS assay., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: D-lactic acidosis, also referred as D-lactate encephalopathy, has been reported in patients with short bowl syndrome (SBS)., Case Report: The neurologic symptoms include altered mental status, slurred speech, and ataxia. Onset of neurological symptoms is accompanied by metabolic acidosis and high anion gap. We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: A recently-introduced quality assessment system (Intelligent Quality Management: iQM), was evaluated in routine clinical use at four different hospitals. The iQM technology is designed to replace conventional external liquid controls with software, Process Control (PC) Solutions and Calibration Validation components that continually assess the function of the GEM Premier 3000 (GEM) analyzer and automatically initiate and document corrective actions., Methods: We validated the performance claims of iQM by monitoring quality control (QC) materials at 4 clinical sites while analyzing approximately 10,550 patient samples. We compared iQM-measured QC values to traditional QC results, evaluating the number and type of error flags for patient samples, and used data from control results to calculate the average time to detect an error (ADT) for each analyte., Results: The calculated ADT was approximately 3 min for all analytes except for sodium (17 min), glucose (11 min), and lactate (5.9 min). Precision of control materials in iQM cartridges was better than from external controls run on traditional analyzers. The iQM system detected errors in 0.46% of actual clinical samples., Conclusions: The findings from our study confirm that (a) iQM precision in a clinical setting is comparable to that found in previous studies done in a research setting, (b) the improved precision of control material on the iQM is likely because the internal control fluids are sealed and not susceptible to exposure from handling, and (c) the system detects and often corrects errors in specific samples that might not be reported by traditional analytical systems.