The prognostic significance of immune microenvironment in breast ductal carcinoma in situ.

Background: The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS.

Methods: A well characterised DCIS cohort (n = 700) with long-term follow-up comprising pure DCIS (n = 508) and DCIS mixed with invasive carcinoma (IBC; n = 192) were stained immunohistochemically for CD20, CD3, CD4, CD8, FOXP3, PD1 and PDL1.

Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity.

Clozapine is an atypical antipsychotic metabolized by CYP1A2, CYP2D6, and CYP2C19 enzymes. Among 66 adult schizophrenia patients treated with clozapine-based combination therapies, we explored the impact of genotype-predicted CYP1A2, CYP2D6, and CYP2C19 activity on dose-adjusted clozapine concentrations and symptom severity, with and without correction for inhibitors and inducers of these enzymes. Uncorrected activity scores were not associated with dose-adjusted clozapine concentrations or symptom severity.

Klüver-Bucy Syndrome Following Traumatic Brain Injury: A Systematic Synthesis and Review of Pharmacological Treatment From Cases in Adolescents and Adults.

Klüver-Bucy syndrome (KBS) is a rare clinical presentation following traumatic brain injury (TBI). Symptoms include visual agnosia, placidity, hyperorality, sexual hyperactivity, changes in dietary behavior, and hypermetamorphosis. The purpose of this article was to identify and synthesize the available evidence from case reports and case series on the treatment profile of KBS among adolescents and adults after TBI.

Progression of cardiac allograft vasculopathy assessed by serial three-vessel quantitative coronary angiography.

Background: The purpose of the present study was to assess the short- and long-term progression of cardiac allograft vasculopathy (CAV) using serial 3-vessel quantitative coronary angiography (QCA).

Methods: CAV progression was assessed using serial 3-vessel QCA analysis at baseline, 1-year and long-term angiographic follow-up (8.5±3.

Targeted and global pharmacometabolomics in everolimus-based immunosuppression: association of co-medication and lysophosphatidylcholines with dose requirement.

Introduction: The immunosuppressive therapy with everolimus (ERL) after heart transplantation is characterized by a narrow therapeutic window and a substantial variability in dose requirement. Factors explaining this variability are largely unknown.

Objectives: Our aim was to evaluate factors affecting ERL metabolism and to identify novel metabolites associated with the individual ERL dose requirement to elucidate mechanisms underlying ERL dose response variability.

Does centrifugation matter? Centrifugal force and spinning time alter the plasma metabolome.

Background: Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.

Aim: Determine whether routinely used plasma centrifugation protocols (1500× 10 min; 3000× 5 min) influence non-targeted metabolomic analyses.

Methods: Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.

Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation.

Background: Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients.

CYP3A5*3 and POR*28 genetic variants influence the required dose of tacrolimus in heart transplant recipients.

Background: After heart transplantation (HTx), the interindividual pharmacokinetic variability of immunosuppressive drugs represents a major therapeutic challenge due to the narrow therapeutic window between over-immunosuppression causing toxicity and under-immunosuppression leading to graft rejection. Although genetic polymorphisms have been shown to influence pharmacokinetics of immunosuppressants, data in the context of HTx are scarce. We thus assessed the role of genetic variation in CYP3A4, CYP3A5, POR, NR1I2, and ABCB1 acting jointly in immunosuppressive drug pathways in tacrolimus (TAC) and ciclosporin (CSA) dose requirement in HTx recipients.