A Bicentric Propensity Matched Analysis of 158 Patients Comparing Porcine Versus Bovine Stented Bioprosthetic Valves in Pulmonary Position.

Background And Objectives: Pulmonary valve replacement (PVR) is the most common operation in adults with congenital heart disease (CHD). There is controversy regarding the best bioprosthesis. We compare the performance of stented bioprosthetic valves (the Mosaic [Medtronic™] porcine pericardial against Carpentier Perimount Magna Ease [Edwards™] bovine) in pulmonary position in patients with CHD.

Predictive value of ERCC2, ABCC2 and MMP2 of response and long-term survival in locally advanced head and neck cancer patients treated with chemoradiotherapy.

Purpose: Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT).

Methods: These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan-Meier and Cox regression analyses to compare genotype groups with the survival.

Efficacy and toxicity of adjuvant chemotherapy on colorectal cancer patients: how much influence from the genetics?

We studied the predictive value for response and toxicity of functional polymorphisms in genes involved in the oxaliplatin/fluorouracil pathway in colorectal cancer patients. One hundred and twenty-seven (127) patients were treated with curative intended surgery followed by adjuvant chemotherapy with FOLFOX (fluorouracil, leucovorin and oxaliplatin) regimen. The median age was 65.

A multicentre prospective study evaluating the impact of proton-pump inhibitors omeprazole and pantoprazole on voriconazole plasma concentrations.

Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantoprazole (n = 25), esomeprazole (n = 3) and no PPI (n = 18).

Impact of CYP2C19 Genotype and Drug Interactions on Voriconazole Plasma Concentrations: A Spain Pharmacogenetic-Pharmacokinetic Prospective Multicenter Study.

Background: Voriconazole, a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by cytochrome P450 (CYP) 2C19. A significant portion of patients fail to achieve therapeutic voriconazole trough concentrations, with a consequently increased risk of therapeutic failure.

Objective: To show the association between subtherapeutic voriconazole concentrations and factors affecting voriconazole pharmacokinetics: CYP2C19 genotype and drug-drug interactions.

Association of GSTP1 and ERCC1 polymorphisms with toxicity in locally advanced head and neck cancer platinum-based chemoradiotherapy treatment.

Background: Platinum-based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous-cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity.

Methods: Thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes were genotyped in 110 patients treated with cisplatin-based CRT.

Longitudinal PET/CT evaluation of TNBS-induced inflammatory bowel disease rat model.

Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract, which two main types are Crohn's disease and ulcerative colitis. It has multifactorial etiologies, being essential the use of animal models and disease activity measures to develop new therapies. With this aim, the use of animal models in combination with non-invasive molecular imaging can play an important role in the development of new treatments.

[Proposal of the SEOM, SEAP and SEFH for the creation of a National Strategy for Precision Medicine in Cancer].

Precision medicine is an emerging approach to the prevention and treatment of disease that takes into account variability in genes, environment and lifestyle for each individual. Precision medicine is transforming clinical and biomedical research, as well as health care itself, from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges.

Review of Intraocular Pharmacokinetics of Anti-Infectives Commonly Used in the Treatment of Infectious Endophthalmitis.

Although intravitreal administration of anti-infectives represents the standard treatment for infectious endophthalmitis, the knowledge about their pharmacokinetics is still limited. In this review, we aimed to summarise the factors influencing the pharmacokinetics of the anti-infective agents. We have conducted a comprehensive review of the preclinical pharmacokinetic parameters obtained in different studies of intravitreal injections of anti-infectives performed on animals, mainly rabbits.

Preclinical characterization and clinical evaluation of tacrolimus eye drops.

Severe allergic ocular diseases as atopic keratoconjunctivitis can induce corneal damage due to inflammatory substances released from giant papillae. Tacrolimus eye drops are one of the current therapeutic alternatives for its treatment. This work is aimed at developing and characterizing a 0.

Ophthalmic Econazole Hydrogels for the Treatment of Fungal Keratitis.

Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration.

Proposal for the Creation of a National Strategy for Precision Medicine in Cancer: a position statement of SEOM, SEAP and SEFH.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges.

[Cysteamine ophthalmic hydrogel for the treatment of ocular cystinosis].

Ocular cystinosis is a rare disease characterised by the deposit of cystine crystals on the corneal surface, which hinder patients' eyesight. Oral cysteamine is given as cysteamine; however, it does not reach the cornea due to the lack of corneal vascularization making necessary its  administration by the topical ocular route. The aim of the present study is to  determine the stability of an ophthalmic hydrogel of cysteamine, which can be  potentially prepared at hospital pharmacy departments, under different preservation conditions during a follow-up of 30 days.

Cysteamine polysaccharide hydrogels: Study of extended ocular delivery and biopermanence time by PET imaging.

Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the lysosomes of various organs, including the cornea. Ocular treatment is based on the administration of cysteamine eye drops, requiring its instillation several times per day. We have introduced the cysteamine in two types of previously developed ocular hydrogels (ion sensitive hydrogel with the polymers gellan gum and kappa-carrageenan and another one composed of hyaluronic acid), aiming at increasing the ocular retention in order to extend the dosing interval.

Preclinical PET Study of Intravitreal Injections.

Purpose: This work aimed at describing the time course of vitreous clearance through the use of positron emission tomography (PET) as a noninvasive tool for pharmacokinetic studies of intravitreal injection.

Methods: The pharmacokinetic profile of intravitreal injections of molecules labeled with 18Fluorine (18F) was evaluated in adult Sprague Dawley rats by using a dedicated small-animal PET/computed tomography scanner. Different conditions were studied: three molecules radiolabeled with 18F (18F-FDG, 18F-NaF, and 18F-Choline), three volumes of intravitreal injections (7, 4, and 2 μL), and absence or presence of eye inflammation (uveitis).

In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops.

Purpose: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops.

Methods: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis.

In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan.

In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology.

Positron Emission Tomography for the Development and Characterization of Corneal Permanence of Ophthalmic Pharmaceutical Formulations.

Purpose: This work is aimed at describing the utility of positron emission tomography/computed tomography (PET/CT) as a noninvasive tool for pharmacokinetic studies of biopermanence of topical ocular formulations.

Methods: The corneal biopermanence of a topical ophthalmic formulation containing gellan gum and kappa carragenan (0.82% wt/vol) labeled with 18Fluorine (18F) radiotracers (18F-FDG and 18F-NaF) was evaluated by using a dedicated small-animal PET/CT, and compared with the biopermanence of an aqueous solution labeled with the same compounds.

Long Survival and Severe Toxicity Under 5-Fluorouracil-Based Therapy in a Patient With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS.

We report the first clinical description of a patient with cancer with a heterozygous germline codon-stop mutation in the TYMS gene. The mutation g.657795_657826del, c.

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan.

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use.

Cyclodextrin-polysaccharide-based, in situ-gelled system for ocular antifungal delivery.

Fluconazole was studied with two different hydrophilic cyclodextrins (hydroxypropyl-β-cyclodextrin (HPBCD) and sulfobutyl ether-β-cyclodextrin (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole-HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural polysaccharides gellan gum and κ-carrageenan.