ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer.

INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

Trajectory of Urine Albumin-Creatinine Ratio in Patients with Acute Heart Failure.

INTRODUCTION: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion. METHODS: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs. RESULTS: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction >50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923). CONCLUSION: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP.

Transition mechanism of the coverage-dependent polymorphism of self-assembled melamine nanostructures on Au(111).

Molecular self-assembled films have recently attracted increasing attention within the field of nanotechnology as they offer a route to obtain new materials. However, careful selection of the molecular precursors and substrates, as well as exhaustive control of the system evolution is required to obtain the best possible outcome. The three-fold rotational symmetry of melamine molecules and their capability to form hydrogen bonds make them suitable candidates to synthesize this type of self-assembled network. In this work, we have studied the polymorphism of melamine nanostructures on Au(111) at room temperature. We find two coverage-dependent phases: a honeycomb structure (α-phase) for submonolayer coverage and a close-packed structure (ß-phase) for full monolayer coverage. A combined scanning tunnel microscopy and density functional theory based-calculations study of the transition regime where both phases coexist allows describing the mechanism underlying this coverage driven phase transition in terms of the changes in the molecular lateral tension.

Pharmacological treatment for challenging behavior in adults with intellectual disability: Systematic review and meta-analysis.

INTRODUCTION: Few evidence on the use of antipsychotics in people with intellectual disabilities and challenging behaviors, generates the need to develop studies that contribute to collect, compare and synthesize the available information. The present systematic review and meta-analysis aims to determine the clinical efficacy of antipsychotic medication in reducing critical episodes in this population. METHODS: We searched Web of Science, Scopus, EBSCO, Embase, and PubMed for randomized controlled trials of antipsychotic medication versus placebo. Preliminarily yielded 1354 abstracts and citations; six studies with 274 subjects met the inclusion criteria of studies with experimental design, longitudinal type, with pre- and post-intervention measurements. RESULTS: There is evidence for the use of psychotropic drugs in the acute management of challenging behaviors in patients with intellectual disability (SMD=-0.85; 95% CI=-1.69 to -0.01; p=0.05). CONCLUSIONS: Our results coincide with the recommendations on the efficacy of the use of antipsychotics. Although our study provides evidence, the limited number of studies included in this research does not allow us to obtain totally conclusive results, although it can be considered as a guide for future studies.

Prognostic significance of plasma chloride in elderly patients hospitalized for acute heart failure.

AIMS: Previous studies demonstrated the relationship between hypochloraemia and poor prognosis in patients hospitalized for acute heart failure (AHF). However, the usefulness of chloride in clinical practice remains uncertain, notably in very old patients with predominantly heart failure (HF) with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic impact of chloride in a cohort of very aged patients with AHF and the possible existence of different phenotypes of hypochloraemia with distinct clinical significance. METHODS AND RESULTS: It was an observational study of 429 patients hospitalized for AHF in which chloraemia was measured. Two different phenotypes of hypochloraemia were identified by their relationship with estimated plasma volume status (ePVS) as a proxy of intravascular congestion. The endpoint of interest was time to all-cause mortality and the composite of death and/or HF readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 85 (78-92) years, 266 (62%) were women, and 80% had HFpEF. After multivariable analysis, chloraemia, but not natraemia, was associated with the risk of death and HF readmission in a U-shaped pattern. The phenotype characterized by hypochloraemia and low ePVS (depletional) was associated with an increased risk of mortality when compared with patients with normochloraemia [hazard ratio (HR) 1.86, P = 0.008]. In contrast, hypochloraemia with high ePVS (dilutional) had no prognostic significance (HR 0.94, P = 0.855). CONCLUSIONS: In very old patients hospitalized with AHF, plasma chloride was associated with the risk of death and HF readmission in a U-shaped pattern and could potentially be used for congestion phenotyping.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Introduction: Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. Methods: We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Results: Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. Discussion: These results support the role of haploidentical donor SCT in children with ALL in CR2.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Diseño y validación de un cuestionario para evaluar el nivel de conocimientos y hábitos de prescripción antibiótica en cirugía oral / Design and validation of a questionnaire to measure antibiotic knowledge and prescribing habits in oral surgery

Introducción: En las últimas décadas, la resistencia antibiótica se ha convertido en un problema mundial para la salud pública. Los odontólogos no deben permanecer ajenos a este grave problema, siendo responsables de en torno al 10 % de las prescripciones antibióticas que se producen en el ámbito extrahospitalario. El propósito del presente estudio fue diseñar y validar un instrumento para analizar los conocimientos y hábitos de prescripción antibiótica en cirugía oral. Material y métodos: El proceso de construcción y validación del instrumento constó de cinco fases: 1) diseño del instrumento a través de una exhaustiva revisión de la literatura publicada entre enero de 2016 y enero de 2021 en las bases de datos PubMed Medline y Cochrane Library; 2) validación del contenido por un grupo de 6 expertos; 3) pretest cognitivo para evaluar la consistencia interna (alfa de Cronbach); 4) evaluación de las propiedades métricas de la escala; y 5) aprobación por el Comité de Ética de la Investigación de la Universidad Europea. Resultados: Se obtuvo un instrumento conformado por 48 ítems: 20 referidos a conocimientos sobre antibioterapia y 28 correspondientes a hábitos de prescripción antibiótica. La validez de contenido del cuestionario, medida por el Índice de Validez de Contenido (CVI), fue de 0,85 con una fiabilidad de 0,80 y una estabilidad temporal casi perfecta (CCI = 0,95). Conclusiones: El riguroso diseño y validación de este estudio proporciona un instrumento con suficiente validez predictiva para su posterior aplicación y evaluación de los conocimientos y hábitos de prescripción antibiótica en cirugía bucal. (AU)

Objective: In recent decades, antibiotic resistance has become a global public health problem. Dentists should not remain oblivious to this serious problem, as they are responsible for around 10 % of antibiotic prescriptions in the out-of-hospital setting. The purpose of the present study was to design and validate an instrument to analyse the knowledge and antibiotic prescribing habits in oral surgery. Material and methods: The process of constructing and validating the instrument consisted of five stages: 1) Design of the instrument through and exhaustive review of the literature published between January 2016 and January 2021 in the PubMed-Medline and Cochrane Library databases; 2) Validation of the content by a panel of 6 experts; 3) Cognitive pretest to assess internal consistency (Cronbach’s alpha); 4) Evaluation of the metric properties of the scale; and 5) Approval by the Research Ethics Committee of the European University. Results: An instrument consisting of 48 items was obtained; 20 referring to knowledge of antibiotic therapy and 28 corresponding to antibiotic prescribing habits. The content validity of the questionnaire, measured by the Content Validity Idex (CVI) was 0.85 with a reliability of 0,80 and almost perfect temporal stability (CCI = 0,95). Conclusions: The rigorous design and validation of this study provides and instrument with sufficient predictive validity for subsequent application and assessment of antibiotic prescribing knowledge and habits in oral surgery. (AU)

Frequency of surgical bone augmentation methods complementary to dental implant placement: A study evaluated with cone beam computed tomography.

Background: The success of dental implants largely depends on the quantity and quality of available bone. Occasionally, it is necessary to perform additional surgical techniques alongside implant placement to increase the available bone volume and ensure the success and survival of treatments. The objective of this study was to evaluate, through cone beam computed tomography, the need for supplementary bone augmentation methods in implant placement. Additionally, the study aimed to assess the frequency of such techniques based on gender, anatomical sectors, and types of bone augmentation procedures. Material and Methods: The analysis included 106 cone beam computed tomography images obtained from 77 patients over the age of 18 who sought oral rehabilitation with implants at the University Clinic of the Master's Program in Oral Implantology at the European University of Valencia. Results: A total of 201 edentulous sextants were analyzed. It was observed that 63.68% of the sextants required a bone augmentation technique, and there was a statistically significant difference (p=0.039) regarding the need for supplementary techniques in women. The need for bone augmentation by sectors was most prevalent the horizontal type (48.11%) and in the mandible (29.41%). About crestal and lateral approaches for sinus elevation, there was a higher need for the lateral technique (49.38%), and a statistically significant difference was evident (p=0.015). Conclusions: A high frequency of bone augmentation need for implant placement was demonstrated. It was shown that some form of supplementary surgical method was required in implant placement (63.68%). The highest need for bone augmentation was observed in the posterior maxillary sector, primarily in the vertical type (29.27%), accompanied by lateral window sinus elevation technique (49.38%). Key words:Bone graft, Dental implant, Guided bone regeneration, Sinus floor augmentation, Cone beam computed tomography.

Dental Transmigration: An Observational Retrospective Study OF52 Mandibular Canines.

The aim of this study was to analyze the prevalence of transmigrated canines in a Spanish population by evaluating their clinical and radiological characteristics. The descriptive observational study obtained 6840 orthopantomographs from all patients seeking dental care in the years 2017-21 via the Patient Reception Service and Dentistry Service at the Faculty of Dentistry at the Complutense University of Madrid and the Central Hospital of the Red Cross of Madrid (Spain). In total, 52 patients presented transmigrated canines, establishing a prevalence of 0.76%. This sample comprised 28 women and 24 men. Whenever a transmigrated canine was identified, a CBCT scan was obtained and used to evaluate the clinical and radiological variables associated with canine transmigration. The predominant side of the transmigration was the left (57.69%) compared to the right side (42.30%). The position of the canine, in order of frequency, according to the Mupparapu classification, corresponded to type IV (42.30%), type II (36.53%), type I (15.38%), and type V (5.76%), with no type III transmigrations found. Clinical manifestations were only recorded in 17.30% of cases, and 11.53% of the radiological findings showed the presence of tooth cysts that were confirmed by histopathological studies. Other impactions, in addition to the transmigrated canine, were found in five patients (9.61%), with the majority being the presence of third molars.

Customized retarders based on waveplates.

Phase control is a critical parameter in polarization measurements. It is well known that a proper combination of wave plates allows to obtain achromatic phase shift, i.e., a constant retardation in certain spectral ranges. This paper is focused on a different, but more useful, goal, as it is to achieve customized variable retarders in broad spectral ranges. To do that, a merit function was used to measure the similarity between the overall phase shift of the wave plate combinations and the desired target. The control variables are the thicknesses and orientations of the wave plates. All possible combinations with four and five wave plates of quartz and MgF2 were analyzed, but our approach can be perfectly extended to deal with more wave plates. The result of an optimization process determines the thicknesses and orientations of the wave plates, which results in the closest retarder to the desired one. Numerical results show deviations below 10% between the target and the obtained retardation. These systems are of special interest in those fields and instruments in which polarization control plays a fundamental role.

Design and Test of a High-Performance Wireless Sensor Network for Irradiance Monitoring.

Cloud-induced photovoltaic variability can affect grid stability and power quality, especially in electricity systems with high penetration levels. The availability of irradiance field forecasts in the scale of seconds and meters is fundamental for an adequate control of photovoltaic systems in order to minimize their impact on distribution networks. Irradiance sensor networks have proved to be efficient tools for supporting these forecasts, but the costs of monitoring systems with the required specifications are economically justified only for large plants and research purposes. This study deals with the design and test of a wireless irradiance sensor network as an adaptable operational solution for photovoltaic systems capable of meeting the measurement specifications necessary for capturing the clouds passage. The network was based on WiFi, comprised 16 pyranometers, and proved to be stable at sampling periods up to 25 ms, providing detailed spatial representations of the irradiance field and its evolution. As a result, the developed network was capable of achieving comparable specifications to research wired irradiance monitoring network with the advantages in costs and flexibility of the wireless technology, thus constituting a valuable tool for supporting nowcasting systems for photovoltaic management and control.

Experiencia del Grupo Español de Trasplante Hematopoyético (GETMON-GETH) en el trasplante alogénico de progenitores hematopoyéticos en leucemia aguda linfoblástica Philadelphia / Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic hematopoietic stem cell transplantation in Philadelphia acute lymphoblastic leukemia

Introducción: Los resultados de los pacientes con diagnóstico de leucemia linfoblástica aguda con cromosoma de Philadelphia (LLA-Ph) continúan siendo desfavorables comparados con los otros tipos de leucemias linfoblásticas agudas, pese a las mejoras en los tratamientos farmacológicos y los avances del trasplante de progenitores hematopoyéticos (TPH).Pacientes y métodos: Se ha analizado el papel del TPH alogénico en pacientes diagnosticados de LLA-Ph mediante un estudio multicéntrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Español de Trasplante Hematopoyético (GETH), diagnosticados de esta enfermedad trasplantados en distintos hospitales españoles entre los años 1998 y 2014.Resultados: La realización del TPH a partir del año 2004, en primera remisión completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impactó favorablemente en la supervivencia global (SG). El TPH a partir del año 2004 en primera RC, así como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administración de imatinib, así como la ausencia de enfermedad mínima residual previas al TPH, junto con la EICRa redujeron la probabilidad de recaída. La edad del paciente inferior a 10 años, el estado de primera RC y el empleo de ATG en el acondicionamiento disminuyeron la mortalidad relacionada con el TPH.Conclusiones: Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicación de TPH debería considerarse en estas situaciones. (AU)

Introduction: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT).Patients and methods: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH).Results: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM).Conclusions: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients. (AU)

Osteosintesis asistida con navegación 2D con tornillos iliacosacros percutáneos en lesiones del anillo pélvico posterior / Assisted osteosynthesis with 2D navigation with percutaneous iliacosacral screws in posterior pelvic ring injuries

Introducción: La osteosíntesis percutánea sacroiliaca guiada por radioscopia en lesiones del anillo pélvico posterior sigue siendo la técnica de referencia. Sin embargo, el desarrollo de técnicas como la cirugía asistida por navegación 2D/3D o por tomografía han mejorado la facilidad y seguridad en la colocación de los tornillos. Objetivo: Presentar la técnica de fijación asistida por navegación en 2D y los resultados clínicos y radiológicos obtenidos. Materiales y métodos: Se revisaron 23 pacientes con disrupción del anillo pélvico posterior (luxación y/o fractura sacroiliaca) intervenidos mediante fijación percutánea asistida por navegación 2D (Sistema Synergy de Medtronic®) en el hospital desde 2017 hasta la actualidad. Se recogieron variables demográficas, de clasificación, terapéuticas y las complicaciones derivadas. Se utilizó la escala modificada de valoración POS (Multicenter Study Group Pelvis Outcome Scale) para evaluar el resultado clínico, radiológico y social. Resultados: Ocho pacientes presentaban luxación sacro-iliaca y 15 tenían fractura a través del sacro. Se implantaron 40 tornillos iliacosacros. El tiempo quirúrgico medio fue de 20 minutos para cada tornillo. Fueron necesarios ocho pulsos de radioscopia de media por intervención. Hubo tres tornillos (7.5%) mal posicionados. 15 pacientes obtuvieron un resultado bueno o excelente en el formulario POS. Conclusiones: La técnica asistida por navegación es una alternativa con buenos resultados. Facilita al cirujano la colocación correcta de los tornillos en el corredor óseo sacro, acortando el tiempo quirúrgico y con una menor exposición a radiaciones ionizantes. Es útil para todo tipo de lesiones del anillo y cuando son necesarias maniobras de reducción.

Introduction: Radioscopy-guided percutaneous sacroiliac osteosynthesis in posterior pelvic ring lesions continues to be the reference technique. However, the development of techniques such as surgery assisted by 2D/3D navigation or tomography have improved the ease and safety in screw placement. Objective: To present the 2D navigation-assisted fixation technique and the clinical and radiological results obtained. Materials and methods: 23 patients with disruption of the posterior pelvic ring (dislocation and/or sacroiliac fracture) who underwent percutaneous fixation assisted by 2D navigation (Medtronic® Synergy System) at the hospital from 2017 to the present were reviewed. Demographic, classification, therapeutic variables and resulting complications were collected. The modified POS (Multicenter Study Group Pelvis Outcome Scale) assessment scale was used to evaluate the clinical, radiological and social outcome. Results: Eight patients had sacro-iliac dislocation and 15 had a fracture through the sacrum. 40 iliacosacral screws were implanted. The average surgical time was 20 minutes for each screw. An average of eight fluoroscopy pulses were necessary per intervention. There were three screws (7.5%) incorrectly positioned. 15 patients had a good or excellent result on the POS form. Conclusions: The navigation-assisted technique is an alternative with good results. It makes it easier for the surgeon to correctly place the screws in the sacral bone corridor, shortening surgical time and with less exposure to ionizing radiation. It is useful for all types of ring injuries and when reduction maneuvers are necessary.

COVID-19 Flow-Maps an open geographic information system on COVID-19 and human mobility for Spain.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has spread all over the world leading to a global pandemic. The fast progression of COVID-19 has been mainly related to the high contagion rate of the virus and the worldwide mobility of humans. In the absence of pharmacological therapies, governments from different countries have introduced several non-pharmaceutical interventions to reduce human mobility and social contact. Several studies based on Anonymized Mobile Phone Data have been published analysing the relationship between human mobility and the spread of coronavirus. However, to our knowledge, none of these data-sets integrates cross-referenced geo-localised data on human mobility and COVID-19 cases into one all-inclusive open resource. Herein we present COVID-19 Flow-Maps, a cross-referenced Geographic Information System that integrates regularly updated time-series accounting for population mobility and daily reports of COVID-19 cases in Spain at different scales of time spatial resolution. This integrated and up-to-date data-set can be used to analyse the human dynamics to guide and support the design of more effective non-pharmaceutical interventions.

Análisis descriptivo del suicidio en el bienio 2018-2019 en Valladolid (España) / Descriptive analysis of suicide in the 2018-2019 biennium in Valladolid (Spain)

Introducción: El suicidio y su prevención suponen un reto esencial en salud pública. Como primera causa externa de muerte en nuestro país, parece escapar a nuestra comprensión y control en vista de los numerosos estudios e intervenciones realizadas. Llevamos a cabo un estudio de los suicidios mortales estudiados por el Instituto de Medicina Legal y Ciencias Forenses de Valladolid durante el bienio 2018-2019. Material y métodos: Se recogieron todas las muertes por suicidio durante 2018-2019 y se cruzaron con los datos anonimizados del Servicio de Psiquiatría del Hospital Clínico Universitario de Valladolid en 2019. Resultados: La tasa de suicidios fue de 8,5/100.000 habitantes, 49 casos en 2018 y 44 en 2019, con una distribución de 3:1 para varones frente a mujeres, principalmente en el medio rural. La franja de edad con mayor incidencia fue la de 31-70 años. La ahorcadura en el medio rural y la precipitación en el urbano fueron los principales métodos. La comorbilidad psiquiátrica identificada más frecuente fueron los trastornos del estado de ánimo-afectivos (F30-39 CIE-10). Conclusiones: Las tasas de suicidio presentan un ligero descenso, mientras que el perfil de riesgo y las características del suicidio mortal se mantienen constantes en nuestro medio más de 20 años después, lo que indica una escasa eficacia de los esfuerzos preventivos realizados hasta ahora. La prevención efectiva del suicidio debe partir de la mejor identificación, prevención y tratamiento de los trastornos psiquiátricos, pudiendo resultar esencial la participación de los Institutos de Medicina Legal y Ciencias Forenses en programas poblacionales multinivel. (AU)

Introduction: Suicide and its prevention are a serious public health challenge. As the primary external cause of death in our country, it seems to be beyond our understanding and control in view of the numerous studies and interventions carried out. We conducted a study of suicide at the Valladolid Institute of Legal Medicine from 2018-2019. Material and methods: All deaths by suicide from 2018-2019 were collected and crossed with anonymized data of the Psychiatry Service of the University Clinical Hospital of Valladolid in 2019. Results: The suicide rate was 8.5/100,000 inhabitants, 49 cases in 2018 and 44 in 2019, with a 3:1 male to female ratio, mainly in rural areas. The age group with the highest incidence was 31-70 years. Hanging in rural areas and precipitation in urban areas were the main methods. Affective disorders (F30-39 ICD-10) were the most common identified psychiatric disorders. Conclusions: Suicide rates are slightly lower, while the risk profile and features of suicide remain constant in our environment more than 20 years later, indicating that preventive efforts carried out have not been completely successful. The effective prevention of suicide must start with better identification, prevention, and treatment of psychiatric disorders, but the contribution of the Institutes of Legal Medicine in the implementation of multilevel population programmes is also essential. (AU)

Germline Predisposition to Pediatric Cancer, from Next Generation Sequencing to Medical Care.

Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, OncoNano V2. The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.

[Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic hematopoietic stem cell transplantation in Philadelphia acute lymphoblastic leukemia]. / Experiencia del Grupo Español de Trasplante Hematopoyético (GETMON-GETH) en el trasplante alogénico de progenitores hematopoyéticos en leucemia aguda linfoblástica Philadelphia.

INTRODUCTION: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH). RESULTS: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM). CONCLUSIONS: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients.