Pharmacokinetic-based Dosing Individualization of Mycophenolate Mofetil in Solid Organ Transplanted Patients.

Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies.

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members.

Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate.

Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution.

External validation of and improvement upon a model for the prediction of placenta accreta spectrum severity using prospectively collected multicenter ultrasound data.

Introduction: This study aimed to validate the Sargent risk stratification algorithm for the prediction of placenta accreta spectrum (PAS) severity using data collected from multiple centers and using the multicenter data to improve the model.

Material And Methods: We conducted a multicenter analysis using data collected for the IS-PAS database. The Sargent model's effectiveness in distinguishing between abnormally adherent placenta (FIGO grade 1) and abnormally invasive placenta (FIGO grades 2 and 3) was evaluated.

Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer.

Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.

Experimental Design: We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts.

The incidence of the thrombophilic SNPs rs6025, rs1799963, rs2066865, rs2289252, and rs8176719 in chronic thromboembolic pulmonary hypertension.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) and venous thromboembolism (VTE) are thought to share many common risk factors. Our study aimed to determine the frequencies of 5 thrombosis-related gene single nucleotide polymorphisms (SNPs) associated with VTE in patients with CTEPH (n 129) compared with a control group of healthy individuals without a history of VTE (n 2637).

Methods: The SNPs of the following genes were investigated: (F V Leiden, rs6025), prothrombin (rs1799963), fibrinogen gamma (FGG, rs2066865), (rs2289252) and (non-O, rs8176719) in both groups.

Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy.

Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities.

The Overexpressed MicroRNAs miRs-182, 155, 493, 454, and U6 snRNA and Underexpressed let-7c, miR-328, and miR-451a as Potential Biomarkers in Invasive Breast Cancer and Their Clinicopathological Significance.

Introduction: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers.

Methods: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data.

Are there Risks from Nanocomposite Restoration Grinding for Dentists?

Objectives: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers.

Materials And Methods: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.

Assessment of urinary 6-oxo-pipecolic acid as a biomarker for ALDH7A1 deficiency.

ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder.

EEG for good outcome prediction after cardiac arrest: A multicentre cohort study.

Aim: Assess the prognostic ability of a non-highly malignant and reactive EEG to predict good outcome after cardiac arrest (CA).

Methods: Prospective observational multicentre substudy of the "Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest Trial", also known as the TTM2-trial. Presence or absence of highly malignant EEG patterns and EEG reactivity to external stimuli were prospectively assessed and reported by the trial sites.

Clinical risk stratification: Development and validation of the DAAE score, a tool for estimating patient risk of transition to secondary progressive multiple sclerosis.

Background: Because secondary progressive multiple sclerosis (SPMS) is associated with worse prognosis, early predictive tools are needed. We aimed to use systematic literature review and advanced methods to create and validate a clinical tool for estimating individual patient risk of transition to SPMS over five years.

Methods: Data from the Jacobs Multiple Sclerosis Center (JMSC) and the Multiple Sclerosis Center Amsterdam (MSCA) was collected between 1994 and 2022.

Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations.

A comprehensive analysis of germline predisposition to early-onset ovarian cancer.

The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.

Raman spectroscopy in lung cancer diagnostics: Can an in vivo setup compete with ex vivo applications?

Lung carcinoma remains the leading cause of cancer death worldwide. The tactic to change this unfortunate rate may be a timely and rapid diagnostic, which may in many cases improve patient prognosis. In our study, we focus on the comparison of two novel methods of rapid lung carcinoma diagnostics, label-free in vivo and ex vivo Raman spectroscopy of the epithelial tissue, and assess their feasibility in clinical practice.

Endometrial stromal tumor with whorling and GREB1::CTNNB1 fusion-a case report on a rare entity.

Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later.

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.

Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues.

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

Background: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model).

Objective: The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer.