Elevated neurofilament light chain associated with cobalt/chromium metal neurotoxicity in a patient with a failed hip implant.

Background: It is known that the heavy metals cobalt and chromium are associated with neurotoxicity. Chromium (Cr) and Cobalt (Co) are both components of metal-on-metal (MoM) implants which can be degraded/fragmented and released into the bloodstream. Neurofilament Light Chain (NfL) is a neuron-specific protein that increases in serum following axonal damage.

Iron and Copper Liver Concentrations in Wilson Disease.

Background And Aims: Wilson disease (WD) results in the defective incorporation of copper into ceruloplasmin as well as decreased biliary copper excretion. Secondary iron overload has also been associated with WD; however, the prevalence is currently unknown. This study aims to determine the prevalence of potential secondary iron overload in patients suspected to have WD.

AI-Augmented Kidney Stone Composition Analysis with Auto-Release Improves Quality, Efficiency, Cost-Effectiveness, and Staff Satisfaction.

Background: We sought to evaluate key performance indicators related to an internally developed and deployed artificial intelligence (AI)-augmented kidney stone composition test system for potential improvements in test quality, efficiency, cost-effectiveness, and staff satisfaction.

Methods: We compared quality, efficiency, staff satisfaction, and financial data from the 6 months after the AI-augmented laboratory test system was deployed (test period) with data from the same 6-month period in the previous year (control period) to determine if AI-augmentation improved key performance indicators of this laboratory test.

Results: In the 6 months following the deployment (test period) of the AI-augmented kidney stone composition test system, 44 830 kidney stones were analyzed.

Total Copper and Labile Bound Copper Fraction as a Selective and Sensitive Tool in the Evaluation of Wilson Disease.

Background: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD).

Methods: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status.

Blood metal concentrations and cardiac structure and function in total joint arthroplasty patients.

Background: There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty (TJA) patients.

Aim: To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.

Methods: The study comprised 110 TJA patients who had a recent history of high chromium, cobalt or titanium concentrations.

Evaluation of polypropylene CSF low-bind collection tubes for trace metal contamination.

Background: Due to the ability of metal ions to cross the blood-brain barrier, there has been interest in analyzing cerebrospinal fluid (CSF) for trace element concentrations to investigate possible correlations with neurodegenerative diseases. In this study, Sarstedt polypropylene CSF collection tubes were analyzed to determine the contamination levels of aluminum, titanium, chromium, manganese, cobalt, nickel, molybdenum, gadolinium, vanadium, arsenic, cadmium, mercury, lead, thallium, selenium, copper, zinc, and iron.

Methods: Sarstedt polypropylene CSF collection tubes from 2 separate lots (n = 10 per lot) were filled with a 2 mL aliquot of a CSF pool with known element concentrations.

Characterization of the alcohol biomarker phosphatidylethanol in donor whole blood and apheresis red blood cells: Implications for transfusion recipients.

Introduction: Phosphatidylethanol (PEth) is a long-term marker of alcohol consumption used frequently in clinical scenarios such as liver transplant evaluation. Recent cases have demonstrated that packed red blood cell (pRBC) transfusion creates the potential for artificial elevation or decrease of observed PEth concentrations in recipients. Very little is known about the prevalence or stability of PEth in pRBCs.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure.

Rapid and Sensitive Detection of Fentanyl and Its Analogs by a Novel Chemiluminescence Immunoassay.

Background: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods.

Methods: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS.

Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults.

Importance: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill.

Objectives: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance.

Design Setting And Participants: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022.

Analysis of Hypoglycemic Drugs by Liquid Chromatography-Tandem Mass Spectrometry.

A rapid and simple method to measure oral hypoglycemic agents is essential in the evaluation of a patient with spontaneous hypoglycemia. As a result, a robust high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the qualitative detection of first-generation sulfonylureas (e.g.

Population pharmacokinetic model of cefepime for critically ill adults: a comparative assessment of eGFR equations.

Cefepime exhibits highly variable pharmacokinetics in critically ill patients. The purpose of this study was to develop and qualify a population pharmacokinetic model for use in the critically ill and investigate the impact of various estimated glomerular filtration rate (eGFR) equations using creatinine, cystatin C, or both on model parameters. This was a prospective study of critically ill adults hospitalized at an academic medical center treated with intravenous cefepime.

Establishment of a Labile Bound Copper Reference Interval in a Healthy Population via an Inductively Coupled Plasma Mass Spectrometry Dual Filtration-Based Assay.

Context.—: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches.

Artificial elevation of phosphatidylethanol due to red blood cell transfusion.

Introduction: Phosphatidylethanol (PEth) is a marker of alcohol consumption used in clinical and forensic settings. PEth positivity in individuals expected to abstain from alcohol can have serious consequences. PEth is located on erythrocytes, thus packed red blood cell (pRBC) transfusion is a potential cause of false-positive results.

'How to' Guide for Pharmacist-led Implementation of Beta-Lactam Therapeutic Drug Monitoring in the Critically Ill.

Beta-lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta-lactam TDM program. This single-center experience forms the basis of the manuscript which outlines practical considerations involved with implementation, including the pharmacist's role as a leader.

Development of an LC-MS/MS assay with automated sample preparation for phosphatidylethanol (PEth)- Not your typical clinical marker.

Phosphatidylethanol (PEth) is a group of phospholipids formed exclusively in the presence of ethanol on the erythrocyte membrane, making it a direct biomarker for long-term ethanol consumption for which a clinical reference interval has been established. Here, we describe an assay for quantitation for two most abundant PEth homologues, PEth 16:0/18:1 and PEth 16:0/18:2, from human whole blood, and present challenges overcome throughout the development process. Since PEth is localized within erythrocyte membranes, a reliable sample preparation technique is an important aspect of PEth analysis.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs.

Correlation of Blood Metal Concentrations with Cognitive Scores and Neuroimaging Findings in Patients with Total Joint Arthroplasty.

Total joint arthroplasty (TJA) implants are composed of metals, ceramics, and/or polyethylene. Studies suggest that the debris released from metal implants may possess neurotoxic properties with reports of neuropsychiatric symptoms and memory deficits, which could be relevant to Alzheimer's disease and related dementias. This exploratory study examined the cross-sectional correlation of blood metal concentrations with cognitive performance and neuroimaging findings in a convenience sample of 113 TJA patients with history of elevated blood metal concentrations of either titanium, cobalt and/or chromium.

What's in your water? A well-known risk for arsenic toxicity.

Arsenic cannot be tasted, seen or smelled and can vary in concentration between water wells even in condensed areas. American domestic well water is not regulated to meet the same drinking water standards as other types of water supplies and often contains arsenic. If arsenic is not detected in a well water sample, it is unlikely to be found later.

Cross-sectional association between systemic metal concentrations and immune markers in patients with total joint arthroplasty.

Total joint arthroplasty (TJA) implants are composed of metal components. Although they are regarded safe, the long-term immunological effects of chronic exposure to the specific implant materials are unknown. We recruited 115 hip and/or knee TJA patients (mean age 68 years) who provided a blood draw for measurement of chromium, cobalt, titanium concentrations, inflammatory markers and systemic distribution of immune cells.

Elementary Overview of Heavy Metals.

Background: Exposure to heavy metals is common as a result of environmental contamination of air, water, and soil as well as accumulation in food, tobacco, herbal medicines, and occupational contact. However, clinically relevant toxicity is much less prevalent. Toxic effects, when they occur, may present with non-specific symptoms, resulting in a very large differential for clinicians to consider.

Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America.

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in Cu in comparison to previously published healthy adult copper isotopic composition.