Acute intoxication caused by three common synthetic cannabinoids: The experience of a large, urban, tertiary care hospital.

BACKGROUND: Synthetic cannabinoids (SC) are chemical substances, which activate cannabinoid receptors in a similar fashion to tetrahydrocannabinol, but with increased efficacy, and are used as illicit recreational drugs. OBJECTIVE: Our objective was to characterize the clinical manifestations and management of three specific, common SC exposures in a cohort of patients presenting to the emergency department of our institution. METHODS: Retrospective case series of patients admitted to an urban tertiary care center between August 1, 2018 and December 31, 2021, with confirmed SC use and positive urinary immunoassay testing for AB-FUBINACA, 4F-MDMB-BUTINACA and ACHMINACA. RESULTS: 58 patients met inclusion criteria during the 3-year study period; median age was 35 years, 60% were male, 31% patients were exposed to >1 substance, and 31% needed hospital addition. The most common physical signs were cardiovascular (54%) and neuropsychiatric (45%). Severe outcomes included coma and seizures, necessitating intubation in 4 patients, and acute renal injury in 7 patients. CONCLUSION: SC are potentially harmful drugs of abuse which can lead to life-threatening complications. Acute care personnel should be aware of the broad range of signs and symptoms of SC use. Testing with short turn around times is available to assess SC use.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

Value of Cerebrospinal Fluid Lactate Levels in Diagnosing Shunt Infections in Pediatric Patients.

OBJECTIVE: The diagnosis and timely treatment of shunt infections (SI) in children is of paramount importance. In some cases, the standard cerebrospinal fluid (CSF) variables will not be sufficient for an accurate diagnosis of SI. CSF lactate (LCSF) has been found to assist in differentiating bacterial from nonbacterial meningitis in non-neurosurgical patients. To the best of our knowledge, the use of lactate in diagnosing or confirming the presence of SI has not yet been discussed. The goal of the present study was to describe the role of LCSF levels in children with shunts and Ommaya reservoirs and to evaluate its role in the accurate diagnosis of shunt-related infection. METHODS: We retrospectively collected data for a consecutive series of pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples from shunts had been collected during a 2-year period (2016-2017). The lactate levels were correlated with the presence of SI. RESULTS: A total of 61 CSF samples were analyzed, with 6 SIs found. The LCSF levels and white blood cell count were both found to correlate with the presence of CSF infections. A cutoff value of ≥2.95 mmol/L reached a sensitivity of 83%, specificity of 83%, and positive predictive value of 50%. LCSF <2.95 mmol/L had a negative predictive value of 96%. CONCLUSIONS: LCSF levels can be used as an additional chemical marker for the diagnosis and confirmation of SIs. An LCSF value of <2.95 mmol/L had a high negative predictive value.

Procollagen C-Proteinase Enhancer 1 (PCPE-1) in Liver Fibrosis.

Fibrosis is characterized by excessive deposition of collagen and additional extracellular matrix (ECM) components in response to chronic injuries. Liver fibrosis often results from chronic hepatitis C virus infection and alcohol abuse that can deteriorate to cirrhosis and liver failure. Current noninvasive diagnostic methods of liver fibrosis are limited in their ability to detect and differentiate between early and intermediate stages of fibrosis. New biomarkers of fibrosis that reflect ECM turnover are therefore badly needed. Procollagen C-proteinase enhancer 1 (PCPE-1), a connective tissue glycoprotein that functions as a positive regulator of C-terminal procollagen processing and subsequent collagen fibril assembly, is a promising candidate. Its tissue distribution and expression profile overlap those of collagen, and its expression in fibrosis is upregulated in parallel to the increase in collagen expression. The potential of PCPE-1 as a biomarker of liver fibrosis was recently established using a CCl4 mouse model of liver fibrosis by showing that the increase in collagen and PCPE-1 content in the fibrotic mouse liver was reflected by elevated plasma levels of PCPE-1. This was achieved using a newly developed highly sensitive, specific, accurate, and reproducible ELISA for mouse PCPE-1, which is based on commercially available antibodies and is offered as a new research tool in the field. A similar ELISA test was developed for human PCPE-1, and preliminary results with plasma from liver fibrosis patients revealed increased plasma concentrations of PCPE-1 in some patients. The protocols of both ELISA tests are outlined herein in great detail to permit their application by any laboratory with similar interests.

Data comparing the plasma levels of procollagen C-proteinase enhancer 1 (PCPE-1) in healthy individuals and liver fibrosis patients.

This article provides a protocol for determination of human procollagen C-proteinase enhancer 1 (PCPE-1) concentrations by ELISA. The inter-assay and intra-assay coefficients of variability are given and so are the average plasma concentrations of PCPE-1 in healthy (control) individuals and liver fibrosis patients.

Correction: Procollagen C-Proteinase Enhancer 1 (PCPE-1) as a Plasma Marker of Muscle and Liver Fibrosis in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0159606.].

Procollagen C-Proteinase Enhancer 1 (PCPE-1) as a Plasma Marker of Muscle and Liver Fibrosis in Mice.

Current non-invasive diagnostic methods of fibrosis are limited in their ability to identify early and intermediate stages of fibrosis and assess the efficacy of therapy. New biomarkers of fibrosis are therefore constantly sought for, leading us to evaluate procollagen C-proteinase enhancer 1 (PCPE-1), a fibrosis-related extracellular matrix glycoprotein, as a plasma marker of fibrosis. A sandwich ELISA that permitted accurate measurements of PCPE-1 concentrations in mouse plasma was established. Tissue fibrosis was assessed using histochemical, immunofluorescence, and immunoblotting analyses for type I collagen and PCPE-1. The normal plasma concentration of PCPE-1 in 6 weeks to 4 months old mice was ~200 ng/ml (189.5 ± 11.3 to 206.8 ± 13.8 ng/ml). PCPE-1 plasma concentrations in four and 8.5 months old mdx mice displaying fibrotic diaphragms increased 27 and 40% respectively relatively to age-matched control mice, an increase comparable to that of the N-propeptide of procollagen type III (PIIINP), a known blood marker of fibrosis. PCPE-1 plasma levels in mice with CCl4-induced liver fibrosis increased 34 to 50% relatively to respective controls and reflected the severity of the disease, namely increased gradually during the progression of fibrosis and went down to basal levels during recovery, in parallel to changes in the liver content of collagen I and PCPE-1. The results favor PCPE-1 as a potential new clinically valuable fibrosis biomarker.

Linearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination.

High-dose busulfan (Bu) is frequently used in preparative myeloablative conditioning (MAC) regimens for patients undergoing hematopoietic stem cell transplantation (HSCT). MAC and reduced-intensity conditioning (RIC) protocols for i.v. Bu infusion have been developed to achieve reliable systemic exposure while minimizing toxicity and treatment failure (relapse). The objectives of the present study were to (1) compare the pharmacokinetics (PK) of i.v. Bu in different dosing protocols, (2) compare intrasubject variability of Bu PK over repeated administrations; (3) examine the effect of concomitant administration of fludarabine on Bu PK, and (4) examine the effect of plasma concentrations of glutathione (GSH), the cosubstrate in Bu metabolism, on Bu clearance. We studied Bu PK twice in each of 46 HSCT patients (after the first and then after the middle dose of the treatment cycle) receiving one of 4 dosing protocols, 2 MAC (cumulative dose, 12.8 mg/kg) and 2 RIC (cumulative dose, 6.4 mg/kg), with daily doses administered either as an individual infusion (3.2 mg/kg) or as 4 infusions of 0.8 mg/kg each. Blood samples were obtained for 6-24 hours after dosing for measurement of Bu plasma concentrations. PK parameters were estimated using compartmental analyses. In a subgroup of patients (n = 14), GSH blood concentrations were determined before Bu administration. Dose- and weight-corrected Bu PK parameters (clearance, 0.173 ± 0.051 L/hour · kg; volume of distribution, 0.71 ± 0.17 L/kg; half-life time, 3.0 ± 0.7 hours) did not differ among treatment protocols (all P >.14) and remained stable between the first and mid-cycle doses. Fludarabine did not affect Bu PK. Blood GSH concentrations before Bu dosing were positively correlated with Bu clearance (adjusted R(2) = 0.45; P = .009). Our data indicate that Bu PK parameters are linear, stable, and predictable in different i.v. protocols and are unaffected by coadministration of fludarabine. Differences in whole blood GSH might contribute to variability in Bu clearance.