Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain.

PURPOSE: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. METHODS: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. RESULTS: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. CONCLUSIONS: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe's Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe - such as the UK or France - are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.

Use of Patent Information to Characterize Trends in the Therapeutic Applications of Extracellular Vesicles Derived from Mesenchymal Stem Cells (MSC-EVs).

Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) are gaining interest for medical purposes. The promising therapeutic effects exhibited in both preclinical and clinical studies have suggested that they may become an alternative for certain applications to cell-based therapies, which are subjected to stricter regulations. The commercial exploitation of these candidates requires a proper patent strategy from both the industry and public research organizations. Here, we performed a global patent literature analysis to identify key players and therapeutic applications in the field. Our results showed an increasing rate of patent publications since 2009, with Asia (specifically China) leading the patenting activity. The therapeutic use of MSC-EVs within patent literature covers a wide range of diseases, in which "Dermal and Wounds," "Neurology" and "Cardiovascular" are the main therapeutic areas. Moreover, most of these patents include "productby- process" claims, since the therapeutic effects of MSC-EVs could be influenced by their manufacturing process. Our results followed scientific and clinical literature trends.

Strontium-Modified Scaffolds Based on Mesoporous Bioactive Glasses/Polyvinyl Alcohol Composites for Bone Regeneration.

In the search of a new biomaterial for the treatment of bone defects resulting from traumatic events, an osteoporosis scenario with bone fractures, tumor removal, congenital pathologies or implant revisions for infection, we developed 3D scaffolds based on mesoporous bioactive glasses (MBGs) (85-x)SiO2-5P2O5-10CaO-xSrO (x = 0, 2.5 and 5 mol.%). The scaffolds with meso-macroporosity were fabricated by pouring a suspension of MBG powders in polyvinyl alcohol (PVA) into a negative template of polylactic acid (PLA), followed by removal of the template by extraction at low temperature. SrO-containing MBGs exhibited excellent properties for bone substitution including ordered mesoporous structure, high textural properties, quick in vitro bioactive response in simulated body fluid (SBF) and the ability of releasing concentrations of strontium ions able to stimulate expression of early markers of osteoblastic differentiation. Moreover, the direct contact of MC3T3-E1 pre-osteoblastic cells with the scaffolds confirmed the cytocompatibility of the three compositions investigated. Nevertheless, the scaffold containing 2.5% of SrO induced the best cellular proliferation showing the potential of this scaffold as a candidate to be further investigated in vitro and in vivo, aiming to be clinically used for bone regeneration applications in non-load bearing sites.

Diseño y validación de la escala pronóstica cubana PREDICMED para estratificar el riesgo de mediastinitis postoperatoria / Design and validation of the Cuban prognostic scale PREDICMED to stratify the risk of postoperative mediastinitis

RESUMEN Introducción: La predicción de fenómenos en las ciencias médicas mediante escalas pronósticas constituye una herramienta valiosa en la actualidad y deben incluirse en el proceso de toma de decisiones. Pronosticar la mediastinitis postoperatoria permite disponer de recursos para su prevención. Objetivo: Construir una escala pronóstica para estratificar el riesgo de padecer mediastinitis postoperatoria. Método: Se realizó un estudio de casos y controles para los factores de riesgo de mediastinitis postoperatoria en el Cardiocentro Ernesto Guevara de Santa Clara, Cuba. Luego de la regresión logística se obtuvo el modelo y, a partir de este, se incluyeron y ponderaron los predictores para obtener la escala cubana pronóstica de mediastinitis postoperatoria: PREDICMED, que se validó por diversos métodos. Resultados: Esta escala se obtuvo con seis predictores y dos estratos de riesgo. Se analizó su rendimiento mediante ajuste, calibración y determinación de su poder discriminante, con buenos resultados. Se realizó validación interna por el método de división de datos y se comparó su capacidad en ambos subconjuntos (desarrollo y validación) sin diferencias. Se probó su buena validez de constructo, al no existir diferencias entre las probabilidades predichas y las observadas. También se analizó su validez de contenido mediante expertos. Por último, se determinó su validez de criterio al comparar con otra escala similar (MEDSCORE). PREDICMED presentó muy buena capacidad discriminatoria (área bajo la curva 0,962) y elevados valores de sensibilidad (84,62%) y especificidad (92,31%). Conclusiones: La escala pronóstica cubana PREDICMED, para estratificar el riesgo de mediastinitis postoperatoria, mostró buenos parámetros de validación y logró estratificar el riesgo en no alto y alto.

ABSTRACT Introduction: Phenomena prediction through prognostic scales is a valuable tool in medical sciences nowadays and it should be included in the decision-making process. Predicting postoperative mediastinitis allows to count on resources for its prevention. Objective: To build a prognostic scale to stratify the risk of suffering from postoperative mediastinitis. Method: A case-control study for the risk factors of postoperative mediastinitis was carried out at the Cardiocentro Ernesto Guevara from Santa Clara, Cuba. After the logistic regression, the model was obtained and from it, the predictors to obtain the Cuban prognostic scale of postoperative mediastinitis PREDICMED were included and weighted, which was validated through several methods. Results: This scale was obtained, counting on six predictors and two risk strata. Its performance was analyzed through adjustment, calibration and determination of its discriminating capacity, showing good results. Internal validation was carried out through the data division method and its capacity was compared in both subsets (development and validation) showing no differences. Its good construct validity was demonstrated, since there were no differences between the predicted and the observed probabilities. Its contents validity was also analyzed by experts. Finally, its criteria validity was determined when compared with another similar scale (Medscore). PREDICMED showed a very good discriminatory capacity (area under the curve 0.962) as well as high values of sensitivity (84.62%) and specificity (92.31%). Conclusions: The Cuban prognostic scale PREDICMED, to stratify the risk of postoperative mediastinitis showed good validation parameters and it was able to stratify the risk in not high and high.

A cost-effectiveness analysis of robotic versus laparoscopic distal pancreatectomy.

AIM: There is no study in the literature that evaluates the cost-effectiveness of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP). We performed a comparative study of RDP and LDP with the aim of evaluating clinical and cost-effective outcomes. MATERIAL AND METHODS: This is an observational, comparative prospective nonrandomized study. The primary end point was to compare the cost-effectiveness differences between both groups. A willingness to pay of €20 000 and €30 000 per quality-adjusted life year (QALY) was used as a threshold to recognize which treatment was most cost-effective. RESULTS: A total of 31 RDP and 28 LDP have been included. The overall mean total cost was similar in both groups (RDP: €9712.15 versus LDP: €9424.68; P > .5). Mean QALYs for RDP (0.652) was higher than that associated with LDP (0.59) (P > .5). CONCLUSION: This study seems to provide data of cost-effectiveness between RDP and LDP approaches, showing some benefits for RDP.

Analysis of economic evaluations of pharmacological cancer treatments in Spain between 1990 and 2010.

Economic evaluation of pharmacological cancer treatment is a critical clinical problem currently under consideration worldwide. We have analysed their main characteristics in Spain between 1990 and 2010 following a systematic review of the 29 complete economic analyses published. The pathology most frequently evaluated was non-small cell lung cancer (31 %). Cost-effectiveness analyses (69 %) were the most frequent analyses. A wide range of incremental cost-effectiveness values (295-160,667 € /QALY) has been reported, and mostly are developed from the perspective of the National Health System (65.5 %). However, none of the studies estimated the indirect costs. The major conclusion is that the absence of regulations concerning the application of the efficiency criterion in decision-making on the subject of price and financing and, most importantly, the fact that these are not included in Spanish hospitals forms make it difficult to analyse the real impact of economic evaluations of cancer treatments on such decisions.

Cuerpo extraño penetrante en el ventrículo izquierdo con evolución crónica inadvertida / Penetrating foreign body in the left ventricle with undetected chronic evolution

Penetrating cardiac trauma constitutes a serious threat for life. Less than the third part of all patients who suffer it arrives at the hospital alive, and half of them die. Most of the penetrating foreign bodies in the heart are metallic, and are frequently caused by firearms and rarely by self-injury. The accidental penetration is uncommon but inadvertent penetration is extremely rare. We present the case of a patient who suffered a closed-chest trauma and did not notice the penetration of a foreign body (copper wire fragment) in the heart. It remained lodged in the left ventricle for more than 3 months. This it is the only case reported in the literature where a strange body: a) crosses the free wall of the right ventricle, the right ventricular cavity, interventricular septum, and the mitral valve apparatus; b) occupies almost all the anteroposterior diameter of the heart, and c) did not produce acute or chronic bleeding.

Aneurisma gigante del apéndice auricular izquierdo / Huge aneurysm of the left atrial appendage

Atrial aneurysms are rare entities that can be congenital or acquired. Those involving the free wall or atrial appendage are even rarer. There are only 49 cases reported in the literature involving the left atrium and 8 in the right atrium until 2002. The most common clinical presentation is the appearance of recurring or incessant atrial arrhythmias. In addition, systemic embolization may occur as an imminent life-threatening event. We present the case of a female teenager who suffered from an embolic stroke during an atrial fibrillation. She had a giant aneurysm of the left atrial appendage that was successfully removed. Images from computed tomography, and of the aneurysm during the surgical intervention are shown.

[Recurrent left atrial myxoma]. / Mixoma auricular izquierdo recidivante.

Primary cardiac tumors are rare. Mixomas are the most common among them; 75% are located in the left atrium, 20% in the right atrium, and the rest in the ventricles. The seldom appear in atrio-ventricular valves. Recidivant mixoma are also rare, appearing in 1-5% of all patients that have undergone surgical treatment of a mixoma. In this paper we present our experience with a female patient, who 8 years after having been operated of a left atrial mixoma, began with symptoms of mild heart failure. Transthoracic echocardiography revealed recurrence of the tumor, and was therefore subjected to a second open-heart surgery from which she recovered without complications.