Environmental contaminants, sex hormones and SHBG in an elderly population.

Introduction: Effects of environmental contaminants (ECs) on endocrine systems have been reported, but few studies assessed associations between ECs and sex hormones (SH) in elderly. Aim of this study was to investigate whether blood concentrations of four classes of ECs were associated with SH concentrations in elderly.

Methods: Samples from participants of the cross-sectional population-based Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 70-year-old men and women, n = 1016) were analyzed using validated mass spectrometry-based methods for SH (testosterone (T), dihydrotestosterone (DHT), estrone and estradiol (E2)); 23 persistent organic pollutants (POPs); 8 perfluoroalkyl substances (PFAS); 4 phthalates and 11 metals.

Acute Renal Thrombotic Microangiopathy Caused by Eltrombopag and Romiplostim in a Patient with Myelodysplastic Syndromes (MDS) and Underlying Antiphospholipid Syndrome.

Unlabelled: Romiplostim and eltrombopag are synthetic agonists of the thrombopoietin receptor (TPO-R), commonly used for immune thrombocytopenic purpura (ITP) and sometimes in myelodysplastic syndrome (MDS). They are rarely associated with kidney injury. We report a case of acute kidney injury caused by romiplostim and eltrombopag in an 80-year-old male patient with MDS and ITP.

Identifying Neutrophil Extracellular Traps (NETs) in Blood Samples Using Peripheral Smear Autoanalyzers.

Neutrophil Extracellular Traps (NETs) are large neutrophil-derived structures composed of decondensed chromatin, cytosolic, and granule proteins. NETs play an important role in fighting infection, inflammation, thrombosis, and tumor progression processes, yet their fast and reliable identification has been challenging. Smudge cells (SCs) are a subcategory of white cells identified by CellaVision, a hematology autoanalyzer routinely used in clinical practice that uses digital imaging to generate "manual" differentials of peripheral blood smears.

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

Elevated serum alpha-fetoprotein (AFP) can be observed in liver cirrhosis and hepatocellular carcinoma (HCC). The glycosylation patterns of AFP have been shown to differentiate these conditions, with AFP glycoforms with core fucosylation (AFP-L3) serving as a malignancy risk predictor for HCC. We have developed a method to detect endogenously present AFP proteoforms and to quantify the relative abundance of AFP-L3 glycoforms (AFP-L3%) in serum samples.

The plasma free fraction of 25-hydroxyvitamin D is not strongly associated with 25-hydroxyvitamin D clearance in kidney disease patients and controls.

Circulating 25-hydroxyvitamin D [25(OH)D] concentration is used to monitor vitamin D status. Plasma protein binding may influence the 25(OH)D dose-response to vitamin D treatment through a direct relationship between the plasma unbound ("free") fraction and clearance of 25(OH)D. We previously evaluated 25(OH)D clearance in relation to kidney function using intravenous administration of deuterium labeled 25(OH)D.

LC-MS/MS Method for High-Throughput Analysis of Methylmalonic Acid in Serum, Plasma, and Urine: Method for Analyzing Isomers Without Chromatographic Separation.

Measurement of methylmalonic acid (MMA) plays an important role in the diagnosis of vitamin B deficiency. Vitamin B is an essential cofactor for the enzymatic carbon rearrangement of methylmalonyl-CoA (MMA-CoA) to succinyl-CoA (SA-CoA), and the lack of vitamin B leads to elevated concentrations of MMA. Measurement of MMA in biological samples is complicated because of the presence of succinic acid (SA), isomer of MMA.

Up-front cell-free DNA next generation sequencing improves target identification in UK first line advanced non-small cell lung cancer (NSCLC) patients.

Background: Genomic sequencing is necessary for first-line advanced non-small cell lung cancer (aNSCLC) treatment decision-making. Tissue next generation sequencing (NGS) is standard but tissue quantity, quality, and time-to-results remains problematic. Here, we compare upfront cell-free-DNA (cfDNA) NGS clinical utility against routine tissue testing in patients with aNSCLC.

Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

Background: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing.

Patients And Methods: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM.

LC-MS/MS Method for Measurement of Thiopurine Nucleotides (TN) in Erythrocytes and Association of TN Concentrations With TPMT Enzyme Activity.

Monitoring concentrations of thiopurine metabolites is used clinically to prevent adverse effects in patients on thiopurine drug therapy. We developed a LC-MS/MS method for the quantification of 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in red blood cells (RBCs). This method utilizes an automated cell washer for RBC separation from whole blood samples and washing of the separated RBCs.

Endogenous sex hormones, aromatase activity and lung cancer risk in postmenopausal never-smoking women.

Although reproductive factors have been repeatedly associated with lung cancer risk, no study to date has directly evaluated the relationship with endogenous sex hormones nor with aromatase activity in postmenopausal never-smoking women. A case-control study of 397 incident lung cancer cases and their individually matched controls, nested within the Shanghai Women's Health Study, was conducted among postmenopausal women who were lifetime never smokers. Prediagnostic concentrations of sex hormones was quantitated using LC-MS/MS assays in plasma.

Clinical Utility and Analytical Aspects of Direct Measurements of Free Hormones Using Mass Spectrometry-Based Methods.

Background: The free hormone (FH) hypothesis states that hormone action and the corresponding biological effects are mediated by the unbound (free) fraction of hormone in circulation. The in vivo relationship between protein-bound and FH is complex and dynamic. In most individuals, measurement of total hormone (TH) is usually adequate to reflect the hormone status; however, certain physiological conditions and/or medications can affect protein binding and alter FH concentration.

Reasons for delayed treatment initiation in Guillain-Barre syndrome.

Objective: The goal of this study was to analyze the reasons for delayed diagnosis of Guillain-Barre syndrome (GBS).

Methods: We retrospectively reviewed the records of all adult patients with GBS treated at Shamir Medical Center (SMC) from 2006 to 2018. We divided the patients into two groups: those with early initiation of treatment (within 24 h of arrival to ED), and those with later initiation of treatment (>24 h after arrival).

A high sensitivity LC-MS/MS method for measurement of 3-methoxytyramine in plasma and associations between 3-methoxytyramine, metanephrines, and dopamine.

Introduction: Diagnosis of pheochromocytoma and paraganglioma (PPGL) is aided by the measurement of metanephrine (MN) and normetanephrine (NMN). Research suggests that 3-methoxytyramine (3MT), a dopamine (DA) metabolite, may serve as a biomarker of metastasis in patients with paraganglioma. Considering the very low endogenous plasma 3MT concentrations (<0.

Thrombosis in myeloproliferative neoplasms: Treatment outcomes of direct oral anticoagulants and vitamin K antagonists.

Background: Patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at an increased risk of recurrent thromboembolic events (TEs) and hemorrhagic complications. Anticoagulation with vitamin K antagonists (VKAs) had been the standard of care until the recent US Food and Drug Administration approval of direct oral anticoagulants (DOACs) for treatment of cancer-associated thrombosis. However, since patients with MPNs were underrepresented in large studies, the use of DOACs in patients with MPN-associated thrombosis remains understudied.

Concentrations of nine endogenous steroid hormones in 70-year-old men and women.

Objectives: Circulating concentrations of endogenous steroids have systemic implications on health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI and to present concentrations in apparently healthy subjects.

Development and Clinical Evaluation of a High-Throughput LC-MS/MS Assay for Vitamin B6 in Human Plasma and Serum.

Background: Pyridoxal 5'-phosphate (PLP) is the primary circulatory form of vitamin B6, an essential cofactor for numerous biochemical enzymatic reactions. Conventional PLP analysis using high-performance liquid chromatography (HPLC) with fluorescence requires derivatization and long injection-to-injection time. Development of high-throughput LC-MS/MS assays is desirable.

Anticoagulation in COVID-19: Effect of Enoxaparin, Heparin, and Apixaban on Mortality.

Background:  Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity.

Objective:  We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity.

Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only.

Background: Developmental exposure to low doses of the endocrine disruptor bisphenol A (BPA) is known to alter bone tissue in young rodents, although how bone tissue is affected in aged animals is not well known. We have recently shown that low-dose developmental exposure to BPA increases procollagen type I N-terminal propeptide (P1NP) levels, a peptide formed during type 1 collagen synthesis, in plasma of 5-week-old female rat offspring while male offspring showed reduced bone size.

Objective: To analyze offspring bone phenotype at 52 weeks of age and clarify whether the BPA-induced increase in P1NP levels at 5 weeks is an early sign of bone marrow fibrosis development.

Prospective analysis of 895 patients on a UK Genomics Review Board.

Background: The increasing frequency and complexity of cancer genomic profiling represents a challenge for the oncology community. Results from next-generation sequencing-based clinical tests require expert review to determine their clinical relevance and to ensure patients are stratified appropriately to established therapies or clinical trials.

Methods: The Sarah Cannon Research Institute UK/UCL Genomics Review Board (GRB) was established in 2014 and represents a multidisciplinary team with expertise in molecular oncology, clinical trials, clinical cancer genetics and molecular pathology.