•A gender-associated bimodal amphetamine/methamphetamine ratio (A/MA) in hair was found.•Odds ratio for women falling into the higher A/MA group is 2.86 times higher.•We hypothesize that gender plays ...a role in CYP2D6-mediated MA N-demethylation to A.
Retrospective analysis of hair testing data provides insights in drugs abuse patterns and improves results interpretation. Cases from subjects undergoing driving fitness assessment (2010–2020) were examined to evidence patterns in methamphetamine (MA) abuse. Materials and Methods: All cases with positive MA (≥0.025 ng/mg) were included (n = 585). Data available were gender, age, MA and A (amphetamine) in hair (h), hair color/treatment, length of proximal hair. Cases with Ah/MAh ≤ 0.35 (n = 469) were arbitrarily selected to remove as many combined A, MA users. ANOVA was performed to detect Ah/MAh predictors. Results: No predictors affected Ah/MAh. A bimodal frequency distribution was observed. We clustered cases in two groups (1, Ah/MAh 0.025–0.070; 2, Ah/MAh 0.071–0.120) and performed logistic regression. Only gender exhibited significant difference across groups (p = 0.0080). Odds ratio for females falling into group 2 was 2.86 times higher (CI97.5 1.34–6.44). Conclusion: Literature data support the hypothesis that the two Ah/MAh groups represent different phenotypes of the CYP2D6-mediated MA N-demethylation. Whether gender plays a role in such difference could not be confirmed. However, these results provide further suggestion of an association of gender and pharmacogenomics with MA disposition, requiring these factors to be considered in future research.
Abstract
Despite liquid chromatography–high-resolution tandem mass spectrometry (MS2) enables untargeted acquisition, data processing in toxicological screenings is almost invariably performed in ...targeted mode. We developed a computational approach based on open source chemometrics software that, starting from a suspected synthetic cannabinoid (SC) determined formula, searches for isomers in different new psychoactive substances web databases, predicts retention time (RT) and high-resolution MS2 spectrum, and compares them with the unknown providing a rank-ordered candidates list. R was applied on 105 SC measured data to develop and validate a multiple linear regression quantitative structure–activity relationship model predicting RT. Competitive Fragmentation Modeling for Metabolite Identification (CFM-ID) freeware was used to predict/compare spectra with Jaccard similarity index. Data-dependent acquisition was performed with an Agilent Infinity 1290 LC-6550 iFunnel Q-TOF MS with ZORBAX Eclipse-Plus C18 (100 × 2.1 mm2/1.8 µm) in water/acetonitrile/ammonium formate gradient. Ability of the combined RT/MS2 prediction to identify unknowns was evaluated on SC standards (with leave-one-out from the RT model) and on unexpected SC encountered in real cases. RT prediction reduced the number of isomers retrieved from a group of new psychoactive substances web databases to one-third (2,792 ± 3,358→845 ± 983) and differentiated between SC isomers when spectra were not selective (4F-MDMB-BUTINACA, 4F-MDMB-BUTINACA 2ʹ-indazole isomer) or unavailable (4CN-Cumyl-B7AICA, 4CN-Cumyl-BUTINACA). When comparing 30/40 eV measured spectra of 99 SC against RT-selected, CFM-ID predicted spectra of isomers, the right candidate ranked 1st on median and 4th on average; 54% and 88% of times the right match ranked 1st or within the first 5 matches, respectively. To our knowledge, this is the first case of extensive chemometrics application to toxicological screening. In most cases, presumptive identification (being based on computation, it requires further information for confirmation) of unexpected SC was achieved without reference measured information. This method is currently the closest possible to true unbiased/untargeted screening. The bottleneck of the method is the processing time required to predict mass spectra (ca. 30–35 s/compound using a 64-bit 2.50-GHz Intel® Core™ i5-7200U CPU). However, strategies can be implemented to reduce prediction processing time.
The application of Quantitative Structure-Property Relationship (QSPR) modeling to the prediction of reversed-phase liquid chromatography retention behavior of synthetic cannabinoids (SC), and its ...use in aiding the untargeted identification of unknown SC are described in this paper. 1D, 2D molecular descriptors and fingerprints of 105 SC were calculated with PaDEL-Descriptor, selected with Boruta algorithm in R environment, and used to build-up a multiple linear regression model able to predict retention times, relative to JWH-018 N-pentanoic acid-d5 as internal standard, under the following conditions: Agilent ZORBAX Eclipse Plus C18 (100 mm × 2.1 mm I.D., 1.8 μm) column with Phenomenex SecurityGuard Ultra cartridge (C18, 10 mm × 2.1 mm I.D., < 2 μm) kept at 50°C; gradient elution with 5-mM ammonium formate buffer (pH 4 with formic acid) and acetonitrile with 0.01% formic acid, flow rate 0.5 mL/min. The model was validated by repeated k-fold cross-validation using two-thirds of the compounds as training set and one-third as test set (Q2 0.8593; root mean squared error, 0.087, ca. 0.56 min; mean absolute error, 0.060) and by predicting relative Retention Times (rRT) of 5 SC left completely out of the modeling study. Application of the model in routine work showed its capacity to discriminate isomers, to identify unexpected SC in combination with mass spectral information, and to reduce the length of the list of candidate isomers to ca. one-third, thus reducing significantly the time required for predicting high-resolution product ion spectra to be compared to the unknown using a computational Mass Spectrometry (MS) search/identification approach.
MRI of the gastrointestinal tract is gaining clinical acceptance and is increasingly used to evaluate patients with suspected small-bowel diseases. MRI may be performed with enterography or ...enteroclysis, both of which combine the advantages of cross-sectional imaging with those of conventional enteroclysis. In this paper, MRI features of primary small-bowel neoplasms, the most important signs for differential diagnosis and the diseases that can be considered as mimickers of small-bowel neoplasms, are discussed.
Primary small bowel tumors account for 1-6% of all Gastrointestinal (G.I.) tract malignancies. Among these pedunculated lipomas are unusual. We report a case of a 66-year-old male with a history of ...G.I. hemorrhage and acute anemia, negative upper and lower endoscopies and a pedunculated lipoma in distal ileum, revealed by CT enterography. The patient was successfully treated by open surgery. Patients with G.I. hemorrhage and negative upper and lower endoscopies need an accurate evaluation of small bowel. Multislice CT enterography or Magnetic Resonance enteroclysis/ enterography represent the fastest and more accurate tools to obtain an exhaustive evaluation of small bowel. In case of small bowel tumors this diagnostic procedures can show site and stage and can even suggest histological type of such neoplasms, with a significant impact in the surgical planning, avoiding time consuming surgical exploration. In this patient multislice TC enterography allowed a correct diagnosis of benign lipoma due to its radiological density and absence of infiltration of the intestinal wall and surrounding tissues.
CT enterography, Gastrointestinal hemorrhage, Lipoma, Small bowel.
The primary role of imaging in identification as well as in characterization adrenal lesions has been demonstrated by several studies. The recent technologic progress has allowed to identify adrenal ...lesions even when they are very small, with a consequent conspicuous increase of the frequency of incidentalomas. Computed Tomography, Magnetic Resonance and Nuclear Medicine are routinely used to evaluate adrenal glands and their pathologic conditions. The aim of this article is to show how the imaging is employed to assess adrenal masses, with special regard to the contribution given by Computed Tomography (CT) and Magnetic Resonance (MR) imaging to the differential diagnosis between benignant and malignant lesions.
Background: In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor ...scintigraphy (SRS) is considered the ‘gold standard’ imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. Patients and methods: Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. Results: SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. Conclusions: Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.
In more than 20% of all patients, the Crohn's disease presents before the age of 18years. The diagnosis and management of Crohn's disease in children has changed dramatically over the last decade, ...mainly due to increased awareness, availability of newer diagnostic modalities such as magnetic resonance imaging (MRI) and newer, more powerful treatments such as biologics. Imaging of the small bowel is needed for diagnosis, management, follow-up and also evaluation of the disease in terms of location, extent, activity and complications. We review all the methods (barium examinations, ultrasonography, computed tomography, MR, and computed tomography- positron emission tomography) commonly used for imaging the small bowel in paediatric patients with Crohn's disease analyzing the advantages and disadvantages of each modality, with particular emphasis on MR imaging.
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