Economic evaluation of percutaneous cryoablation vs conventional surgery in extra-abdominal desmoid tumours in the Spanish healthcare system

BackgroundDesmoid tumours (DTs) or deep fibromatosis are benign soft-tissue tumours, sometimes locally aggressive, requiring intervention on some cases. Surgery has been the gold standard, but new less invasive techniques such as percutaneous cryoablation have proved their effectiveness, reducing health resources and complications. The study aimed to compare the total cost of percutaneous cryoablation and conventional surgery for patients with extra-abdominal and/or abdominal wall DTs, candidates for local ablative treatment in Spain.MethodsA cost-analysis model was developed. An expert panel provided data about resource consumption for the percutaneous cryoablation technique and validated the epidemiology used for target population estimation. Unitary resources cost (euro 2022) derived from local cost databases. A retrospective analysis of 54 surgical cases in 3 Spanish hospitals was performed to estimate the cost of conventional surgery based on the cost of the Diagnosis-Related group (DRG) codes identified on this patient sample, weighted by each DRG proportion. The total cost for each alternative included intervention cost and complications cost, considering debridement required in 4.5% of cases with percutaneous cryoablation and minor surgery for surgical site infection in 18.0% for conventional surgery.ResultsThe total cost for percutaneous cryoablation (euro 5774.78/patient-year) was lower than the total cost for conventional surgery (euro 6780.98/patient-year), yielding cost savings up to euro 80,002 in 1 year for the entire cohort of 80 patients with DTs eligible for intervention estimated in Spain. One-way sensitivity analyses confirmed the results' robustness.ConclusionPercutaneous cryoablation versus conventional surgery would yield cost savings for the management of DT patients in Spain.Critical relevance statementThis manuscript provides insight into the economic impact derived from the savings related to the use of percutaneous cryoablation for desmoid-type tumours from the perspective of the Spanish National Healthcare System, providing useful information for the health decision-making process.Key points center dot Desmoid tumours are locally aggressive and may require local therapy.center dot Percutaneous cryoablation procedure is less invasive than the conventional surgery.center dot Cost comparison shows savings associated to percutaneous cryoablation use.Key points center dot Desmoid tumours are locally aggressive and may require local therapy.center dot Percutaneous cryoablation procedure is less invasive than the conventional surgery.center dot Cost comparison shows savings associated to percutaneous cryoablation use.Key points center dot Desmoid tumours are locally aggressive and may require local therapy.center dot Percutaneous cryoablation procedure is less invasive than the conventional surgery.center dot Cost comparison shows savings associated to percutaneous cryoablation use

The polyadenylation factor FIP1 is important for plant development and root responses to abiotic stresses

17 Pág.Root development and its response to environmental changes is crucial for whole plant adaptation. These responses include changes in transcript levels. Here, we show that the alternative polyadenylation (APA) of mRNA is important for root development and responses. Mutations in FIP1, a component of polyadenylation machinery, affects plant development, cell division and elongation, and response to different abiotic stresses. Salt treatment increases the amount of poly(A) site usage within the coding region and 5' untranslated regions (5'-UTRs), and the lack of FIP1 activity reduces the poly(A) site usage within these non-canonical sites. Gene ontology analyses of transcripts displaying APA in response to salt show an enrichment in ABA signaling, and in the response to stresses such as salt or cadmium (Cd), among others. Root growth assays show that fip1-2 is more tolerant to salt but is hypersensitive to ABA or Cd. Our data indicate that FIP1-mediated alternative polyadenylation is important for plant development and stress responses.This research was supported by grants from the Spanish Government (BIO2017-82209-R and BIO2014-52091-R to J.C.P.) and by the "Severo Ochoa Program for Centres of Excellence in R&D” from the Agencia Estatal de Investigación of Spain (grant SEV-2016-0672 (2017-2021)) to the CBGP. B.T. was supported by a predoctoral fellowship (BES-2012-054056) from MINECO (Spain). C.M. was supported by a Marie Skłodowska-Curie fellowship (Root Barriers 655406) from the European Commission. S.M.B is supported by an Howard Hughes Medical Institute (HHMI) Faculty Scholar Fellowship.Peer reviewe

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

Treatment of bone tumours by radiofrequency thermal ablation

Radiofrequency thermal ablation (RFTA) is considered the treatment of choice for osteoid osteomas, in which it has long been safely used. Other benign conditions (chondroblastoma, osteoblastoma, giant cell tumour, etc.) can also be treated by this technique, which is less invasive than traditional surgical procedures. RFTA ablation is also an option for the palliation of localized, painful osteolytic metastatic and myeloma lesions. The reduction in pain improves the quality of life of patients with cancer, who often have multiple morbidities and a limited life expectancy. In some cases, these patients are treated with RFTA because conventional therapies (surgery, radiotherapy, chemotherapy, etc.) have been exhausted. In other cases, it is combined with conventional therapies or other percutaneous treatments, e.g., cementoplasty, offering faster pain relief and bone strengthening. A multidisciplinary approach to the management of these patients is recommended to select the optimal treatment, including orthopaedic surgeons, neurosurgeons, medical and radiation oncologists and interventional radiologists

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES) : comprehensive genetic analysis by next-generation sequencing of 480 patients

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Intervencionismo guiado por tc en el manejo del dolor lumbar

Revisión bibliográfica. Investigación en diagnóstico por la imagenEn este trabajo se ha hecho una revisión bibliográfica narrativa sobre el dolor lumbar, las causas del mismo, su diagnostico por imagen, el tratamiento general del dolor lumbar, y por ultimo nos hemos centrado en las técnicas intervencionistas guiadas por TC, que se pueden realizar para el manejo del dolor lumbar, dentro del ámbito de la radiología musculoesquelética, en colaboración multidisciplinar con otras especialidades que manejan el dolor lumbar. La búsqueda bibliográfica se ha realizado en la base de datos PubMed y los criterios de búsqueda han sido; Low back pain, facet joint syndrome, Computed Tomogrphy, Magnetic resonance Imaging, Spine, epidural injections, rhizolysis, vertebroplasty.Universidad de Granada. Departamento de Radiología y Medicina Física. Máster Avances en Radiología diagnóstica y terapéutica y medicina física, curso 2012-201