The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Report of consensus panel 2 from the 11th international workshop on Waldenström's macroglobulinemia on the management of relapsed or refractory WM patients.

The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.

Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management.

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials.

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.

Near-optimal feedback control for postprandial glucose regulation in type 1 diabetes.

This paper is focused on feedback control of postprandial glucose levels for patients with type 1 Diabetes Mellitus. There are two important limitations that make this a challenging problem. First, the slow subcutaneous insulin pharmacokinetics that introduces a significant lag into the control loop. Second, the positivity constraint on the control action, meaning that it is not possible to remove insulin from the body. In this paper, both issues are explicitly considered in the design process using the internal model control framework, to derive a near-optimal feedback controller. Optimality is understood here as minimizing the blood glucose peak after a meal intake and, at the same time, preventing glucose values below a prescribed threshold. It is shown how the proposed controller approaches the optimal closed-loop performance as a limit case. The theoretical results are supported by a numerical example and the feasibility of the overall strategy under uncertainties is illustrated using an extended version UVa/Padova metabolic simulator.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Atrapamiento de catéter de Swan-Ganz durante cirugía valvular mitral: a propósito de un caso / Swan-Ganz Catheter Entrapment during mitral valve surgery: a case report

El catéter de Swan-Ganz es un dispositivo ampliamente utilizado para la monitorización del paciente crítico, así como durante lasintervenciones de cirugía cardiovascular. Sin embargo, su implantación y uso no están exentos del desarrollo de complicaciones.Presentamos un caso de atrapamiento del catéter con la sutura de cierre de la atriotomía izquierda durante una intervención de sustitución valvular mitral. (AU)

The Swan-Ganz catheter is a widely used device for monitoring critical patients, as well as during cardiovascular surgery. However,its implantation and use are not exempt from the development of complications. We present a case of catheter entrapment with theclosing suture of the left atriotomy during a mitral valve replacement procedure. (AU)

Masas cardiacas. experiencia monocentro (Parte I) / The heart masses. single centre study (Part I)

Introducción. Las masas cardiacas son una patología poco frecuente, entre las que destacan los tumores cardiacos (TC), que sonen su conjunto los más frecuentes entre ellas. En un segundo artículo hablaremos de los TC. Material y métodos. Se repasan lasprincipales causas de masas cardiacas y dentro de ellas, se hará en otro trabajo una revisión de los diferentes TC. Entre las masascardíacas tenemos variantes anatómicas de la normalidad, estructuras extracardíacas, material iatrogénico o extraño, vegetaciones, quistes hidatídicos miocárdicos/pericárdicos, trombos en diferentes cavidades, tumores pericárdicos y finalmente TC. Se revisanalgunas masas cardiacas, previamente definidas, ocurridas en un hospital universitario de tercer nivel, a lo largo de 37 años, enlos que se han realizado 8.000 intervenciones con circulación extracorpórea, más algunos casos previamente comunicados por elprimer autor. Resultados. Describimos la experiencia del servicio de cirugía cardiovascular del Hospital Universitario de Canarias,que tiene casuística con ejemplos de la mayoría de los casos arriba enumerados. Conclusiones. Las masas cardiacas son poco frecuentes, pero un centro hospitalario con suficiente trayectoria puede acumular casuística de la mayoría. (AU)

Introduction. Cardiac masses are a rare pathology, among which cardiac tumors (CT) stand out, which are the most frequentamong them. In a second chapter we will talk about CT. Material and methods. The main causes of cardiac masses are reviewedand within them, a review of the different CT will be done in the next paper. Cardiac masses include anatomical variants of normality, extracardiac structures, iatrogenic or foreign material, vegetations, myocardial/pericardial hydatid cysts, thrombi in differentcavities, pericardial tumors, and finally CT. Some previously defined cardiac masses that occurred in a tertiary university hospitalover 37 years in which 8,000 interventions with extracorporeal circulation have been performed, plus some cases previously reported by the first author, are reviewed. Results. We describe the casuistry of the cardiovascular surgery service of the HospitalUniversitario de Canarias, which includes examples of most of the cases listed above. Conclusions. Cardiac masses are rare, but ahospital center with sufficient experience can accumulate casuistry of the majority. (AU)

Los tumores cardiacos (parte de las masas cardiacas). Experiencia monocentro (Parte II) / The heart tumors (part of the cardiac masses). Single centre study (Part II)

Introducción. Las masas cardiacas son una patología poco frecuente, entre las que destacan los tumores cardiacos (TC), que sonen su conjunto los más frecuentes entre ellas. La mayoría de TC es metastático. Entre los TC primitivos, el 75% es benigno. Material y métodos. Se analiza la experiencia con los TC del Hospital Universitario de Canarias (HUC) en Tenerife, a lo largo de 37años y casi 8,000 intervenciones con circulación extracorpórea (CEC), más algunos casos previamente comunicados por el primerautor. Los TC más frecuentes intervenidos han sido los mixomas. Se analiza retrospectivamente esta serie utilizando el programade análisis estadístico SPSS Statistics v20. Resultados. Se operaron 83 mixomas desde marzo1984 (inicio del programa de CEC)hasta diciembre de 2021 (1-6 cada año; 2,13/año). Edad 34-62 años, media 48,73. Varones 33(39,86%). Mujeres 50(60,24%).De ellos, 77 fueron en aurícula izquierda (75 en septo). Tres en aurícula derecha. Otros 3 en septo interauricular con crecimientoen ambas aurículas). Ninguno en ventrículos. Se siguieron 76 pacientes (96,1%). Hubo una muerte intrahospitalaria (1,2%) y dosen el seguimiento por causa no relacionada. En la curva de seguimiento de Kaplan-Meier, el 88% puede llegar a los 36 meses deseguimiento (95% de IC). Se repasan también algunos tumores menos frecuentes. Conclusiones. Aunque los TC benignos lo seanhistológicamente, clínicamente pueden no serlo si causan mortalidad o daño grave. El pequeño riesgo quirúrgico justifica la intervención ante el riesgo de no hacerlo. (AU)

Introduction. Cardiac masses are a rare pathology, among which cardiac tumors (CT) stand out, which are the most frequentamong them. Most tumors are metastatic. Among primitives, 75% are benign. Material and methods. The experience with CT atthe Hospital Universitario de Canarias (HUC) in Tenerife, over 37 years and almost 8,000 extracorporeal interventions, plus somecases previously reported by the first author, are reviewed. The most frequent CTs operated on have been myxomas. This series isretrospectively analyzed using the statistical analysis program SPSS Statistics v20. Results. 83 myxomas were operated on, fromMarch 1984 (beginning of the extracorporeal surgery program) to December 2021 (1-6 each year; 2.13/year). Age 34-62 years,mean 48.73. Men 33 (39.86%). Women 50 (60.24%). Of these, 77 were in the left atrium (75 in the septum). Three in the rightatrium. Another 3 in the interatrial septum with growth in both atria). 76 patients (96.1%) were followed up. There was one in-hospital death (1.2%) and two in follow-up due to unrelated causes. In the Kaplan-Meier follow-up curve, 88% can reach 36 monthsof follow-up (95% CI). Some less frequent tumors are also reviewed. Conclusions. Although benign CTs are histologically benign,they may not be clinically so if they cause mortality or serious damage. The small surgical risk justifies the intervention given therisk of not doing it. (AU)

Management of mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a kidney recipient: a case report.

Mixed acute rejection is a clinicopathological entity that is difficult to accurately diagnose, and so may be under-reported. Allografts are lost more often than in either humoral or cellular rejection. The diagnosis requires both histological and immunological studies on renal biopsy and blood specimens from the transplant recipient to provide the required rescue therapy to abolish the allogeneic response against the graft. We present a clinical case report of an active mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a patient with a kidney transplant. The patient was diagnosed, treated, and followed up as per the local institution's procedure with a full recovery of graft function. Our case emphasises the challenge of a mixed acute rejection and supports the need to improve the post-transplant outcome of recipients and their grafts.

L-Dopa release from mesoporous silica nanoparticles engineered through the concept of drug-structure-directing agents for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease, the 2nd most common after Alzheimer's disease, the main effect of which is the loss of dopaminergic neurons. Levodopa or l-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine. However, over time the efficacy of the medication gradually decreases requiring modified delivery methods. One of the major challenges for the medication to work is to achieve a gradual continuous supply of l-Dopa to the brain to minimise symptoms. Herein, mesoporous silica nanoparticles (MSNs) were engineered through the concept of drug-structure-directing agents (DSDAs) with inherent therapeutic activity. The DSDA used was l-Dopa drug modified by amidation with fatty acids to build anionic surfactants that were able to form micelles as templates for the assembly of inorganic precursors to form the silica framework. This templating route produced MSNs with tunable sizes ranging from 100 nm to 1 µm and with different shapes: spherical, with either solid structures with radial mesopores and porous shells, or hollow-shells with inside large void cavities; and elongated, characterized by long hollows covered by mesoporous shells. The concept of using DSDAs to synthesize drug nanocarriers can be used to avoid the surfactant removal and subsequent drug loading steps involved in the synthesis of conventional MSNs. We hypothesized that the l-Dopa released from MSN materials is mediated by the size and solubility of the DSDAs, and the surface chemical interactions between the DSDAs and MSN hosts. Different pHs (acidic and neutral) simulating gastrointestinal tract conditions were tested, and the results showed hardly any release for gastric conditions at pH 1.2, avoiding the premature release in the stomach typical of conventional MSNs, while for intestinal conditions of pH 7.4, the release of l-Dopa occurred in a continuous and sustained manner, which is well suited to the drug's application and delivery route, and matches well with achieving a sustained l-Dopa delivery to relief symptoms. This could open up new uses for MSNs synthesized by this approach to treat PD.

Impact of the COVID-19 pandemic on the care of cancer patients in Spain.

BACKGROUND: Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. MATERIALS AND METHODS: This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. RESULTS: Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. CONCLUSIONS: This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.

Castilla y León, su tributo al desarrollo quirúrgico europeo. Su evolución hasta la ilustración / Castile and Leon in the development of surgery at europe. His evolution to enlightennment

A través de la Escuela de Traductores de Toledo y del Monasterio de Nuestra Señora de Guadalupe, antes del desarrollo de las universidades, se iniciaron el conocimiento anatómico humano y la cirugía, conocimientos que llegan a Europa. El desarrollo de la cirugía en la Corona de Castilla y en parte también en la Corona de Aragón en el siglo XVI y en menor medida en el siglo XVII es brillante, en comparación con la del resto de Europa, coincidiendo con el denominado “siglo de oro español”. Pero al no adoptar a tiempo en 1620 el nuevo pensamiento inductivo descrito por Bacon en su “Novum Organum”, que revolucionó las Ciencias, el desarrollo quirúrgico posterior ha sido menor. Aunque hemos tenido cirujanos formados fuera, el desarrollo institucional, en cuantoa ser nosotros los pioneros, ha sido poco frecuente. Carecemos de una previsión estratégica adecuada para revertir esa carencia inicial a la entrada de la Edad Moderna. Lo que ha hecho que se adoptasen las evidencias científicas, anatómicas, histológicas, farmacológicas, médicas y quirúrgicas con más de un siglo de retraso. (AU)

Through the Toledo School of Translators and the Monastery of Our Lady of Guadalupe, before the development of universities, human anatomical knowledge and surgery began, knowledge that reaches Europe.The development of surgery in the Crown of Castile and partly also in the Crown of Aragon in the 16th century and to a lesser extent in the 17th century is brilliant, compared to the rest of Europe, coinciding with the so-called “ Spanish golden age ”. But by not adopting in time in 1620 the new inductive thinking described by Bacon in his “Novum Organum”, which revolutionized the Sciences, subsequent surgical development has been less. Although we have had surgeons trained outside, institutional development, in terms of being the pioneers, has been rare. We lack an adequate strategic foresight to reverse this initial deficiency at the beginning of the Modern Age. Which has led to the adoption of scientific, anatomical, histological, pharmacological, medical and surgical evidence with more than a century of delay. (AU)

¿Un nuevo factor de riesgo quirúrgico: la polución del aire. ¿Lo debemos tener en cuenta? / A new surgical risk factor: air pollution. Should we consider it as such?

La polución atmosférica incrementa la mortalidad global por cualquier causa. En especial la debida a causas de origen respiratorio y cardiovascular. Los pacientes que ingresan por una isquemia miocárdica aguda hacen con más frecuencia insuficiencia cardiaca aguda en aquellos pacientes en los que se encuentran partículas de polución en sus alveolos. Su significado entre los pacientes que se operan de patologías graves o están muy frágiles o con mucha comorbilidad está sin estudiar. Se plantea formar un comité de expertos que verifique en episodios de polución atmosférica en que proporción ésta influye en los resultados. Y si es así, incorporarlo en los predictores de riesgo quirúrgico. Más adelante se deben proponer medidas de como evitarlo y tratarlo. (AU)

Air pollution increases global mortality from any cause. Especially due to causes of respiratory and cardiovascular origin. Patients admitted for acute myocardial ischemia more frequently experience acute heart failure in those patients in whom pollution particles are found in their alveoli. Its significance among patients who undergo surgery for serious pathologies or who are very fragile or with a lot of comorbidity has not been studied. It is proposed to form a committee of experts to verify in episodes of atmospheric pollution in what proportion it influences the results. And if so, incorporate it into the predictors of surgical risk. Later, measures should be proposed on how to avoid it and treat it. (AU)

La cirugía en la España de los siglos XVIII y XIX. Papel de la universidad, la armada y las reales academias / Surgery in Spain in the XVIII and XIX centuries. Role of the university, the navy and the royal academies

El Protomedicato era el Tribunal, cuyos miembros estaban sancionados por el rey, que se encargaba de controlar la docencia y el ejercicio profesional médico. Este hecho cambió claramente en la Nueva España a partir del siglo XVIII. En España, a mediados del mismo siglo, la universidad perdió parte de su papel controlador cuando la Corona encargó la formación quirúrgica a una serie de cirujanos educados en Europa. Esto lo hizo a través de los Reales Colegios de Cirujanos de la Armada, siendo el primero de ellos elde Cádiz. Estos poseían su propio Protomedicato y seleccionaban a los candidatos a ser estudiantes de medicina. Incluso tuvieron su propio Bachiller en Artes, imprescindible para la carrera médica. Su esquema pasó a la Nueva España a finales de ese siglo. Por otra parte, a finales del siglo XVII se funda lo que sería el embrión de la primera Real Academia de Medicina y Cirugía en Sevilla, en controversia con la universidad, donde se discutía sobre el avance en el campo de la medicina y de la cirugía y se enseñaban los nuevos conceptos histológicos, químicos, botánicos y farmacológicos, y también los quirúrgicos. Todo ello dio un vuelco a la cirugía. (AU)

The Protomedicato was the Court, whose members were sanctioned by the king, who was in charge of controlling teaching and medical professional practice. This fact clearly changed in New Spain from the 18th century on. In Spain in the mid-18th century, the university lost part of its controlling role when the Crown commissioned surgical training from a number of European-educated surgeons. This was done through the Royal Colleges of Surgeons of the Navy, the first of them being that of Cádiz. They had their own Protomedicato and selected candidates to be medical students. They even had their own Bachelor of Arts, essential to be able to be a medical student. His scheme passed to New Spain at the end of that century. On the other hand, at the end of the 17th century, what would be the embryo of the first Royal Academy of Medicine and Surgery in Seville was founded, in controversy with the university, where the advancement in the field of medicine and new histological, chemical, botanical and pharmacological concepts were taught, as well as surgical ones. all this turned the surgery upside down. (AU)

Data on natural radionuclide's activity concentration of cement-based materials.

Cement based materials may contain varying levels of radionuclides, mainly 226Ra (from the 238U series), 232Th and 40K, which are used to determine the Activity Concentration Index ("ACI"). According to the European directive Euratom 2013/59 in these materials, the "ACI" must be < 1 to be suitable for their use in construction. In this paper, data on the activity concentration of natural radionuclides in cement-based materials (i.e. cements, additions, pigments and aggregates) as well as their chemical composition are presented. Radioactivity measurements have been determined by using gamma spectroscopy the chemical compositions have been determined by X-Ray Fluorescence. Data for cements measured shown that white cements present a lower concentration of activity than conventional CEM I. In addition, the CAC (Calcium aluminate cements) present high activity concentration in the 232Th series. Regarding additions, FA (Fly Ash) are those that present the highest concentration of activity in the 238U and 232Th series, while olive biomass ashes are those supplementary cementitious materials that show the highest concentration of activity for 40K. Some pigments used in mortar and concrete technology were also characterized. Granitic and volcanic rocks, potentially used as aggregates present much higher activity concentration than the siliceous aggregate.

Association of autologous punch grafting, TLC-NOSF dressing and multitype compression therapy to rapidly achieve wound closure in hard-to-heal venous leg ulcers.

OBJECTIVE: To document the efficacy of a combined therapeutic strategy in achieving rapid wound healing in patients with long-standing ulcers. MATERIALS AND METHODS: Outpatients with hard-to-heal venous leg ulcers were included in an interventional, prospective, single-arm, mono-centre study and treated with autologous punch grafting, TLC-NOSF dressing and multi-type compression therapy. The primary outcome was the percentage of healed wounds by week 12. Secondary outcomes included time-to-reach wound closure, wound area reduction, treatment acceptability and safety. RESULTS: From November 2018 to October 2019, 42 patients with 51 ulcers were included (23 males, 70.6±40.8 years old, with multiple comorbidities). Despite poor wound healing prognosis at baseline (47% of recurrent ulcers, with a mean duration of 15 months and a mean area of 12.6cm2), wound healing was achieved in 47 ulcers (92%) after a mean period of treatment of 25±13 days. A relative wound area reduction>75% was also reached in three additional ulcers by the last evaluation visit. No adverse event related to the procedure was reported throughout the study period. The associated treatment were very well tolerated and accepted by the patients. CONCLUSIONS: The evaluated procedure induced fast re-epithelisation of the treated ulcers. Based on our experience, this simple and successful reparative strategy may be considered as an interesting option in the treatment of venous leg ulcers of poor prognosis.