Estudio del Ductus Arterioso Persistente en la clínica de pequeños animales

El ductus arterioso (ductus) es un conducto que comunica las arterias aorta y pulmonar durante la vida fetal y debe cerrarse tras el nacimiento. Cuando esto no ocurre, pasa a ser una estructura patológica denominada ductus arterioso persistente (DAP), que representa la alteración cardiaca congénita más frecuente en la especie canina. El objetivo de este trabajo fue realizar una revisión bibliográfica sobre el DAP en esta especie, tratando su origen y las opciones diagnósticas y terapéuticas disponibles actualmente. Para ello, se realizó una consulta de la bibliografía de referencia y una búsqueda de publicaciones en bases de datos. Además, se han incluido imágenes ecográficas de casos atendidos en el Hospital Veterinario de la Universidad de Zaragoza. La persistencia del ductus se debe en gran medida a una deficiencia de tejido muscular en su pared. El paso de sangre a través del DAP es inicialmente en sentido izquierda-derecha por la mayor presión de las cámaras izquierdas del corazón. Si esta situación persiste, la presión en la arteria pulmonar aumenta y el flujo se invierte (derecha-izquierda), lo cual es más grave (síndrome de Eisenmenger). El diagnóstico del DAP incluye anamnesis, exploración completa del paciente, pruebas laboratoriales, electrocardiograma y pruebas de diagnóstico por imagen. Estas últimas constituyen una herramienta de gran utilidad: la radiología permite valorar la existencia de dilatación de cámaras cardiacas y arterias, y de edema pulmonar asociado; con la ecografía se puede detectar su localización, valorar la funcionalidad cardiaca y descartar otras patologías; y la resonancia magnética y la tomografía computerizada con multidetectores permiten realizar un estudio más profundo. Cuando la comunicación es izquierda-derecha, el tratamiento del DAP consiste en su cierre mediante ligadura quirúrgica o técnicas mínimamente invasivas. En la comunicación derecha-izquierda, el cierre del DAP está contraindicado, por lo que el tratamiento de elección será el farmacológico

Actualización del hipertiroidismo felino

En este trabajo se ha realizado una revisión bibliográfica sobre el hipertiroidismo felino abordando la etiopatogenia, la epidemiología, los signos clínicos, el diagnóstico, el tratamiento y el pronóstico. El hipertiroidismo es la enfermedad endocrina más frecuente en gatos geriátricos (mayores de 8 años), con una prevalencia descrita de aproximadamente el 10% (14% en gatos de más de 13 años). Esta endocrinopatía se caracteriza por una producción y secreción excesiva de hormonas tiroideas, que con mayor frecuencia se debe a un adenoma o a una hiperplasia adenomatosa de la glándula tiroides. No obstante, también puede deberse a un carcinoma tiroideo. De acuerdo con los estudios que se han realizado sobre las posibles causas de esta enfermedad, su etiología es probablemente multifactorial. Los animales afectados pueden presentar distintos tipos de síntomas que también podrían ser detectables en otras patologías, como pérdida de peso, polifagia, poliuria/polidipsia, etc. Pese a que la enfermedad se desarrolla lentamente, la detección precoz es vital, ya que la probabilidad de una transformación a neoplasia maligna aumenta considerablemente en aquellos casos en los que se ha realizado un diagnóstico tardío o el cuadro clínico se ha mantenido durante mucho más tiempo. El conocimiento de las distintas opciones de diagnóstico (laboratorial y por imagen), tratamiento (paliativo o curativo) y monitorización de esta endocrinopatía aplicables en la práctica clínica veterinaria resulta esencial para abordarla de manera adecuada y acorde a las necesidades de cada caso. Asimismo, el manejo de las posibles enfermedades concomitantes es fundamental para lograr que los gatos afectados tengan una buena calidad de vida. <br /

Masas adrenales en perro y gato: aproximación diagnóstica y manejo clínico

La detección y el diagnóstico de estas alteraciones supone un reto para el veterinario clínico, quien debe conocer muy bien todas las pautas de actuación en cada una de sus diferentes manifestacione

Nuevas alternativas para la monitorización del tratamiento con trilostano en perros con hiperadrenocorticismo

El Servicio de Endocrinología del Hospital Veterinario de Zaragoza plantea un nuevo protocolo para el control de la respuesta al trilostano en perros con síndrome de Cushing, cuyo objetivo principal es averiguar el momento en el que existe una mayor correlación entre la respuesta clínica y los niveles de cortisol sanguíneo

Effect of Cytochrome P450 and ABCB1 Polymorphisms on Imatinib Pharmacokinetics After Single-Dose Administration to Healthy Subjects

Background: Validated genomic biomarkers for oncological drugs are expanding to improve targeted therapies. Pharmacogenetics research focusing on the mechanisms underlying imatinib suboptimal response might help to explain the different treatment outcomes and drug safety profiles. Objective: To investigate whether polymorphisms in genes encoding cytochrome P450 (CYP) enzymes and ABCB1 transporter affect imatinib pharmacokinetic parameters.Methods: A prospective, multicenter, pharmacogenetic pilot study was performed in the context of two separate oral imatinib bioequivalence clinical trials, which included 26 healthy volunteers. DNA was extracted in order to analyze polymorphisms in genes CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and ABCB1. Imatinib plasma concentrations were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods using WinNonlin software. Results: Volunteers (n = 26; aged 24 ± 3 years; 69% male) presented regular pharmacokinetic imatinib data (concentration at 24 h, 436 ± 140 ng/mL and at 72 h, 40 ± 26 ng/mL; AUC0-72 32,868 ± 10,713 ng/mL⋅h; and Cmax 2074 ± 604 ng/mL). CYP2B6 516GT carriers showed a significant reduction of imatinib concentration at 24 h (23%, 391 ng/dL vs 511 ng/dL in 516GG carriers, p = 0.005) and elimination half-life (11%, 12.6 h vs 14.1 h in 516GG carriers, p = 0.041). Carriers for CYP3A4 (*22/*22, *1/*20 and *1/*22 variants) showed a reduced frequency of adverse events compared to *1/*1 carriers (0 vs 64%, p = 0.033). The other polymorphisms analyzed did not influence pharmacokinetics or drug toxicity. Conclusion: CYP2B6 G516T and CYP3A4 *20,*22 polymorphisms could influence imatinib plasma concentrations and safety profile, after single-dose administration to healthy subjects. This finding needs to be confirmed before it is implemented in clinical practice in oncological patients under treatment with imatinib

El complejo respiratorio ovino

Esta enfermedad es un proceso grave que afecta a corderos e individuos adultos, cuyo origen está en el aparato respiratorio y se caracteriza por ser multifactorial y de etiología plural. Su control es muy complejo y repercute de forma importante en la viabilidad de las explotaciones

Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.

Introduction Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%–75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%–30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%–55% of variability in voriconazole metabolism. Materials and methods The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. Conclusion This trial will provide information about the viability and cost-effectiveness of the mplementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. Ethics and dissemination A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. Trial registration number Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.post-print441 K

A case-control of patients with COVID-19 to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease: a propensity score matching analysis

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying condition

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49-5956·71) in the IG and 7298·22 BAU/mL (6739·41-7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.Funded by Instituto de Salud Carlos III (ISCIII). AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017), the State Plan for Research, Development, and Innovation 2013−16, the State Plan for Scientific and Technical Research and Innovation 2017−20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELER ATE and INsTRuCT received funding from the EU’s Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Instituto de Salud Carlos III is the Spanish partner in the VACCELERATE project. This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III − ISCIII −), (grants PI19CIII/00004 to JA and PI21CIII/00025 to MPO and JGP), and COVID-19 FUND (grants COV20/00679 and COV20/00072 to MPO and JA) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The authors thank all trial participants, the international data safety monitoring board (Appendix 1 p 23), and the trial steering committee (Appendix 1 pp 24−25). The authors thank Esther Prieto for editorial assistance and writing support (employed by Hospital Universitario La Paz; funded by the Instituto de Salud Carlos III, grant number PCT20/00018) and María Castillo-de la Osa (PEJ2018-004557-A) for excellent technical assistance.S