Report from the HarmoSter study: different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; however, unifying calibration is a double-edged sword.

Objectives: Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS).

Macro-TSH: An Uncommon Explanation for Persistent TSH Elevation That Thyroidologists Have to Keep in Mind.

A macro-thyroid-stimulating hormone (macro-TSH) is an infrequent yet noteworthy phenomenon in the thyroid field. A 69-year-old patient presented with persistently elevated thyroid-stimulating hormone (TSH) levels ranging from 30 to 50 mIU/L, paradoxically accompanied by normal thyroid hormone levels and normal thyroid ultrasound, with no findings on pituitary magnetic resonance. Laboratory studies were conducted to investigate potential interferences impacting the accuracy of TSH measurements.

Longitudinal Postvaccine SARS-CoV-2 Immunoglobulin G Titers, Memory B-Cell Responses, and Risk of COVID-19 in Multiple Sclerosis Over 1 Year.

Background And Objectives: Some disease-modifying treatments impair response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. We aimed to investigate longitudinal SARS-CoV-2 antibody dynamics and memory B cells after 2 and 3 messenger RNA (mRNA) vaccine doses and their association with the risk of COVID-19 in patients with MS on different treatments over 1 year.

Methods: Prospective observational cohort study in patients with MS undergoing SARS-CoV-2 mRNA vaccinations.

Doll Therapy Intervention Reduces Challenging Behaviours of Women with Dementia Living in Nursing Homes: Results from a Randomized Single-Blind Controlled Trial.

Background: Doll therapy (DT) is a non-pharmacological intervention for the treatment of the behavioural and psychological symptoms of dementia (BPSD). We designed a single-blind randomized controlled trial of the 30-day efficacy of DT in reducing the BPSD, professional caregivers’ distress and patients’ biomarkers of stress, and in improving the exploration and caregiving behaviours. Methods: We randomly assigned 134 women with moderate-to-severe dementia living in nursing homes (NHs) to a DT intervention (DTI, 67) or a sham intervention with a cube (SI, 67).

Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone.

Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration.

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2.

Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.

A description of Cannabinoid levels in Cannabis oil by high-performance liquid chromatography-mass spectrometry in a reference laboratory of North-Italy.

Background: Cannabis oils from FM2®, Bedica®, Bediol®, Bedrocan®, Bedrolite® and Pedanios 22/1® are largely used for medical purposes such as spasticity, chronic pain and appetite stimulating. Several studies showed cannabinoids action on CB1 and CB2 receptors reduces the hyperalgesic phase in inflammatory pain, leading to an improvement of conditions. The active compounds of these galenic preparations show a high variability making titration mandatory.

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy.

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR.

Report from the HarmoSter study: impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone.

Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention.

30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.

Lack of concordance between EMIT assay and LC-MS/MS for Therapeutic Drug Monitoring of Mycophenolic Acid: Potential increased risk for graft rejection?

Therapeutic drug monitoring (TDM) of immunosuppressive drugs is crucial in organ-transplanted patients to prevent rejection or toxic effects due to inadequate dosage. Mycophenolic acid (MPA) is a commonly used immunosuppressant in this setting. Nowadays, MPA concentrations are monitored by Enzyme Multiplied Immunoassay Technology (EMIT), and Liquid Chromatography (LC)-based techniques, particularly coupled to Tandem Mass Spectrometry (LC-MS/MS).

25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland.

Doll therapy intervention for women with dementia living in nursing homes: a randomized single-blind controlled trial protocol.

Background: Doll therapy is a non-pharmacological intervention for people with dementia aimed to reduce distressing behaviours. Reliable results on the efficacy of Doll therapy for people with dementia are needed. The concept of attachment theorised by Bowlby has been proposed to explain the Doll therapy process, but it has not been proven to influence the response to doll presentation.

LC-MS application for therapeutic drug monitoring in alternative matrices.

Nowadays the practice of therapeutic drug monitoring, consisting in the measurement of drugs concentrations in biological matrices in order to guide possible posological adjustments, is becoming more and more important for the management and optimization of several treatments, especially when drugs with narrow therapeutic indexes are administered. Although TDM on plasma samples is currently considered the gold standard, this practice shows some limitations: it requires venous blood sampling, centrifugation and, if necessary, shipment with refrigeration; moreover, drug concentrations in plasma or blood do not necessarily reflect the ones in the target tissues or cells. Therefore, in the recent years great attention has been given to alternative matrices for TDM purpose, in order to reduce invasiveness, costs or to obtain better information about drug concentrations at the active sites.

Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic hepatitis C-affected patients treated with new drugs.

Purpose: Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated with new anti-HCV drugs.

Methods: Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1, CYP24A1 and GC genes were assessed through real-time PCR.

Clinical endocrinology and hormones quantitation: the increasing role of mass spectrometry.

Clinical endocrinology has always had a close relationship with laboratory medicine. In fact, the quantification of hormones is of great importance for diagnosis, treatment, recurrence and patient's prognosis of endocrine disorders. This review dealt with the role of the laboratory in diagnosing endocrine pathologies related to adrenal gland, pituitary, gonads and thyroid.

Matrix effect management in liquid chromatography mass spectrometry: the internal standard normalized matrix effect.

LC-MS is becoming a standard for many applications, thanks to high sensitivity and selectivity; nevertheless, some issues are still present, particularly due to matrix effect (ME). Considering this, the use of optimal internal standards (ISs, usually stable-isotope labeled) is important, but not always possible because of cost or availability. Therefore, a deep investigation of the inter-lot variability of the ME and of the correcting power of the chosen IS (isotope-labeled or not) is mandatory.

SANIST: optimization of a technology for compound identification based on the European Union directive with applications in forensic, pharmaceutical and food analyses.

Electrospray Ionization and collision induced dissociation tandem mass spectrometry are usually employed to obtain compound identification through a mass spectra match. Different algorithms have been developed for this purpose (for example the nist match algorithm). These approaches compare the tandem mass spectra of the unknown analyte with the tandem mass spectra spectra of known compounds inserted in a database.

[Benign tumors of vulva: review and case report of achrocordon].

The vulvovaginal region is a very complex area because of its anatomy and the fact that it can be source of a large number of benign tumors and less frequent malignant tumors. In recent decades, there have been significant gains in the diagnosis and treatment of vulvovaginal tumors, thanks to the contributions of cellular and molecular biology. The purpose of this review article is to serve as a practical reference for clinical and pathological diagnosis as well as in the outpatient treatment and monitoring of these benign tumors.

Vitamin D status among children and adolescents on anticonvulsant drugs in southern Switzerland.

Introduction: It is recognised that vitamin D status is often inadequate (<50 nmol/l) in epileptic children, mainly because some anticonvulsant drugs induce the enzymes responsible for its metabolism. The purpose of the present study was to address vitamin D status among children and adolescents treated with anticonvulsant drugs and control subjects who reside in southern Switzerland, a high solar radiation region.

Methods: Between January and May 2013, total serum 25-hydroxyvitamin D was assessed by liquid chromatography-tandem mass spectrometry in 58 children and adolescents with epilepsy and 29 controls residing in southern Switzerland.

Interstitial fluid obtained from kidney biopsy as new source of renal biomarkers.

Introduction: Development of renal biomarkers is required to improve on diagnostic accuracy, prognosis and prediction of response to therapy in renal disease. We describe a new method of obtaining from renal specimens a biologic fluid potentially enriched in secreted proteins.

Methods: A renal biopsy specimen was centrifuged, and the interstitial fluid (IF) obtained was evaluated by SELDI-ToF, 1D and 2D gel electrophoresis.

Regulation of breast cancer response to chemotherapy by fibulin-1.

Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1-binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls.

Surface-activated chemical ionization and high-flow gradient chromatography to reduce matrix effect.

The new atmospheric pressure chemical ionization source, named surface-activated chemical ionization (SACI), has been used in conjunction with high-flow gradient chromatography to reduce the matrix effect. This high-flow gradient chromatography approach avoids the co-elution of analyte and biological matrix compounds that leads to a reduction in quantitation errors due to matrix effect. However, this approach cannot be employed with the classical electrospray ionization (ESI) source that usually works at low eluent flow (< 300 microL/min).