35 research outputs found

    A survey of gastroprotective drugs: prescription-indication in hospitalized patients

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    La prescripción de fármacos antiulcerosos en medio hospitalario, y su influencia posterior en atención primaria, se incrementó en los últimos años y con ello el gasto farmacéutico. El objetivo del presente estudio es analizar la prevalencia de prescripción de antiulcerosos en nuestro centro hospitalario y la adecuación a las indicaciones establecidas. Se realizó un estudio observacional de prescripción-indicación con 2 cortes transversales separados en 6 meses para evitar sesgos de selección. Se constata el uso elevado de gastroprotectores, principalmente inhibidores de bomba de protones, sobre todo en profilaxis de gastropatía por antiinflamatorios no esteroideos (AINE) (17,1%), con una tasa de prescripciones incorrectas del 77,6% a pesar de la existencia de un protocolo específico elaborado por el comité de farmacia y terapéutica de nuestro centro. Destaca el número elevado de prescripciones en pacientes con corticoterapia sin asociación con AINE (25,7%). Se requieren nuevas herramientas que impliquen al facultativo y a los gestores clínicos en el uso racional de medicamentosPrescription rates of antiulcer drugs in hospitals and their spill-over to general practice have risen over the last few years, increasing pharmaceutical expenses. The aim of this study was to analyze gastroprotective drug prescription habits in our hospital by assessing both prevalence and adherence to approved indications. An observational study of prescription-indication was performed with 2 cross sections separated by 6 months to avoid selection bias. We found overprescription of gastroprotective drugs, mainly proton pump inhibitors for the prevention of non-steroidal antiinflammatory drug-induced ulcer (17.1%). Overall, 77.6% of prescriptions had no acceptable indication, despite the availability of a specific protocol produced by the Pharmacy and Therapeutics Committee in our center. There was a high prevalence of prescriptions for non-approved indications such as prophylaxis in patients administered cor-ticosteroids without non-steroidal anti-inflammatory agents (25.7%). New programs to train clinicians and clinical mana-gers in rational drug use are requiredS

    Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson’s disease

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    AbstractAluminum and zinc have been related to the pathogenesis of Parkinson’s disease (PD), the former for its neurotoxicity and the latter for its apparent antioxidant properties. 6-Hydroxydopamine (6-OHDA) is an important neurotoxin putatively involved in the pathogenesis of PD, its neurotoxicity often being related to oxidative stress. The potential effect of these metals on the oxidative stress induced by 6-OHDA autoxidation and the potential of ascorbic acid (AA), cysteine, and glutathione to modify this effect were investigated. Both metals, particularly Al3+, induced a significant reduction in ⋅OH production by 6-OHDA autoxidation. The combined action of AA and a metal caused a significant and sustained increase in ⋅OH generation, particularly with Al3+, while the effect of sulfhydryl reductants was limited to only the first few minutes of the reaction. However, both Al3+ and Zn2+ provoked a decrease in the lipid peroxidation induced by 6-OHDA autoxidation using mitochondrial preparations from rat brain, assessed by TBARS formation. In the presence of AA, only Al3+ induced a significant reduction in lipid peroxidation. After intrastriatal injections of 6-OHDA in rats, tyrosine hydroxylase immunohistochemistry revealed that Al3+ reduces 6-OHDA-induced dopaminergic lesion in the striatum, which corroborates the involvement of lipid peroxidation in 6-OHDA neurotoxicity and appears to discard the participation of this mechanism on PD by Al3+ accumulation. The previously reported antioxidant properties of Zn2+ appear to be related to the induction of Zn2+-containing proteins and not to the metal per se

    Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant

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    Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromisedThis research was funded by the Instituto de Salud Carlos III and the European Regional Development Fund, FEDER (grant number PI081449), and an intramural grant from the Xunta de Galicia (grant number ED431B 2020/37). S.S.I. was awarded a Research Fellowship by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP)S

    Celia’s Encephalopathy (BSCL2-Gene-Related): Current Understanding

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    Seipin, encoded by the BSCL2 gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia’s encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia’s encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorderThis work was supported by the Instituto de Salud Carlos III and the European Regional Development Fund, FEDER (grant numbers PI10/02873 and PI13/00314), by the Consellería de Industria, Xunta de Galicia (grant numbers 10PXIB208013PR, ED341b 2017/19 and ED431B 2020/37), and by Fundación Mutua Madrileña (Call 2015). S.S.I. was awarded a Research Fellowship, granted by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP)S

    Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL

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    The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient’s clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this diseaseThis study was supported with a competitive PhD grant from a pre-Doctoral scholarship for research groups of the Health Research Institute of Santiago (IDIS)S

    Competiciones de programación. Estímulo y salida laboral para los alumnos

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    Las competiciones de programación son un estímulo importante para los alumnos de informática. Durante los últimos años ha crecido el número de estas competiciones en su mayoría promovidas por grandes empresas con el propósito de reclutar alumnos brillantes. La International Collegiate Programming Contest es la más antigua de ellas, promovida por la ACM y patrocinada por IBM. A la final mundial van los mejores equipos de cada una de las más de 90 competiciones regionales que tienen lugar por todo el mundo. La regional en la que pueden participar las universidades españolas es la Southwestern Europe Regional Contest (España, Italia, Portugal, Suiza, Francia y Austria). Esta regional fue organizada por la Escola Tècnica Superior d’Enginyeria Informàtica de la Universitat Politècnica de València en su edición de 2012 y lo será también en 2013. En este trabajo se presenta la experiencia de planificación de una regional, tanto a nivel organizativo como de planteamiento de los problemas para la competición. Asimismo, se destaca la importancia de este tipo de competiciones en cuanto al desarrollo de habilidades y destrezas en los alumnos, pues su dedicación a solucionar distintos tipos de problemas, combinando conocimientos de matemáticas con técnicas algorítmicas, les da una formación adicional que saben apreciar las grandes empresas. Algunos alumnos de la ETSInf que han participado en estas competiciones están en proceso o ya han sido contratados por empresas del sector como es Google.SUMMARY -- Programming contests are a good stimulus for computer engineering students. These contests have experienced an expansion during last years thanks to the interest of big companies for hiring brilliant students. The International Collegiate Programming Contest is the oldest one, promoted by ACM and sponsored by IBM. The ACM-ICPC World Final takes place every year, only the best teams can participate, which are selected from the ones who compete in the more than 90 regional contests celebrated around the world. Spanish universities can participate in the Southwestern Europe Regional Contest (Spain, Italy, Portugal, France and Austria). The 2012 edition of this regional contest took place in Valencia, organised by the School of Computer Engineering at the Universitat Politècnica de València. The 2013 edition will be organised in Valencia as well. In this paper it is presented the experience of planning a regional contest, both from the point of view of organisation as from posing the problems. Additionally, it is pointed out the value of this sort of programming contests as they foster the development of some abilities and skills in students, because the time they spend solving problems where the knowledge of mathematical concepts and of algorithmic techniques is very important. This fact gives students a special training very appreciated by big software companies. Some former students from ETSInf who participated in international programming contests were hired or are in process of being hired by Google

    Development of international consensus recommendations using a modified Delphi approach

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    Funding Information: This work was supported by BioMarin Pharmaceutical Inc . Funding Information: The content of this manuscript was based on preparatory pre-meeting activities and presentations and discussions during two advisory board meetings that were coordinated and funded by BioMarin Pharmaceutical Inc. All authors or their institutions received funding from BioMarin to attend at least one or both meetings. Additional disclosures: BKB received consulting payments from BioMarin, Shire, Genzyme, Alexion, Horizon Therapeutics, Denali Therapeutics, JCR Pharma, Moderna, Aeglea BioTherapeutics, SIO Gene Therapies, Taysha Gene Therapy, Ultragenyx, and Inventiva Pharma, participated as clinical trial investigator for BioMarin, Shire, Denali Therapeutics, Homology Medicines, Ultragenyx, and Moderna as well as received speaker fees from BioMarin, Shire, Genzyme, and Horizon Therapeutics. AH received consulting payments from BioMarin, Chiesi, Shire, Genzyme, Amicus, and Ultragenyx, participated as clinical trial investigator for Ultragenyx as well as received speaker fees from Alexion, Amicus, BioMarin, Genzyme, Nutricia, Sobi, and Takeda. ABQ received consulting payments from BioMarin, speaker fees from BioMarin, Nutricia, Vitaflo, Sanofi, Takeda, Recordati, and travel support from Vitaflo . SEC received consulting payments and speaker fees from BioMarin as well as consulting payments from Synlogic Therapeutics. COH was clinical trial investigator for BioMarin and received consulting and speaker payments from BioMarin. SCJH received consulting payments and travel support from BioMarin and Homology Medicines. NL received consulting payments from Alnylam, Amicus, Astellas, BioMarin, BridgeBio, Chiesi, Genzyme/Sanofi, HemoShear, Horizon Therapeutics, Jaguar, Moderna, Nestle, PTC Therapeutics, Reneo, Shire, Synlogic, and Ultragenyx, participated as clinical trial investigator for Aeglea, Amicus, Astellas, BioMarin, Genzyme/Sanofi, Homology, Horizon, Moderna, Pfizer, Protalix, PTC Therapeutics, Reneo, Retrophin/Travere therapeutics, Shire, and Ultragenyx, as well as received speaker fees from Cycle Pharmaceuticals, Leadiant and Recordati. MCM II received consulting payments from BioMarin, Horizon Therapeutics, Rhythm Pharmaceuticals, Applied Therapeutics, Cycle Therapeutics, and Ultragenyx. ALSP received speaker fees from BioMarin. JCR received consulting payments from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, and Nutricia, speaker fees from Applied Pharma Research, Merck Serono, BioMarin Pharmaceutical, Vitaflo, Cambrooke, PIAM, LifeDiet, and Nutricia, as well as travel support from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, Cambrooke, PIAM, and Nutricia. SS received consulting payments, research grants, speaker fees, and travel support from BioMarin and participated as clinical trials investigator for BioMarin. ASV received consulting payments from BioMarin, Horizon Therapeutics, and Ultragenyx and participated as clinical trial investigator for Acadia, Alexion, BioMarin, Genzyme, Homology Medicines, Kaleido, Mallinckrodt, and Ultragenyx. JV received consulting payments from BioMarin, LogicBio Pharmaceuticals, Sangamo Therapeutics, Orphan Labs, Synlogic Therapeutics, Sanofi, Axcella Health, Agios Pharmaceuticals, and Applied Therapeutics as well as travel grants from BioMarin and LogicBio Pharmaceuticals. MW received consulting payments, speaker fees, and travel support from BioMarin, and participated as clinical trial investigator for Mallinckrodt, Roche, Wave, Cycle Therapeutics, and Intrabio. ACM participated in strategic advisory boards and received honoraria as a consultant and as a speaker for Merck Serono, BioMarin, Nestlé Health Science (SHS), Applied Pharma Research, Actelion, Retrophin, Censa, PTC Therapeutics, and Arla Food. Funding Information: Ideally, access to (neuro)psychological/psychiatric support should assist adolescents with identifying, understanding, and reporting of PKU-specific challenges (Table 3), offering individualized recommendations on managing these challenges. Although there is no replacement for mental health services for patients with identified needs, psychosocial support from PKU peers, e.g., through PKU camps, virtual social events, etc., can at least in the short-term help to improve metabolic control by providing individuals an opportunity to participate in supportive PKU-related educational activities potentially reducing perceived social isolation [91]. In addition to PKU camps, which may be very specific to certain regions or countries, HCPs should consider encouraging involvement in local, regional, national and international PKU patient/family advocacy and social support organizations, introducing adolescents and young adults to national/international patient registries [92,93]. Besides support from PKU peers, patients can benefit from non-PKU peer support, although some adolescents and young adults with PKU may not disclose to others and may avoid eating in with others or eating in public due to potential feelings of anxiety or feelings of being ashamed of their disease. In addition, patients with PKU of all ages, but particularly vulnerable adolescents and young adults, can benefit from having the opportunity to learn about and practice strategies that help promote feelings of empowerment and self-efficacy that can be used in both familiar and unfamiliar environments where they may experience peer pressure and feel the need to ‘fit in’. For example, a role-play approach involving behavioral rehearsal, self-monitoring, goal setting, and training in problem-solving skills with emphasis on initiation and inhibition (i.e., how to say no) could be provided by parents, PKU peers, or even members of the PKU team. These types of activities can be used to teach adolescents with PKU how to react in social situations, such as dining out, helping to avoid indulging and increased risk-taking behavior, a hallmark of the adolescent period [94].This work was supported by BioMarin Pharmaceutical Inc.The content of this manuscript was based on preparatory pre-meeting activities and presentations and discussions during two advisory board meetings that were coordinated and funded by BioMarin Pharmaceutical Inc. All authors or their institutions received funding from BioMarin to attend at least one or both meetings. Additional disclosures: BKB received consulting payments from BioMarin, Shire, Genzyme, Alexion, Horizon Therapeutics, Denali Therapeutics, JCR Pharma, Moderna, Aeglea BioTherapeutics, SIO Gene Therapies, Taysha Gene Therapy, Ultragenyx, and Inventiva Pharma, participated as clinical trial investigator for BioMarin, Shire, Denali Therapeutics, Homology Medicines, Ultragenyx, and Moderna as well as received speaker fees from BioMarin, Shire, Genzyme, and Horizon Therapeutics. AH received consulting payments from BioMarin, Chiesi, Shire, Genzyme, Amicus, and Ultragenyx, participated as clinical trial investigator for Ultragenyx as well as received speaker fees from Alexion, Amicus, BioMarin, Genzyme, Nutricia, Sobi, and Takeda. ABQ received consulting payments from BioMarin, speaker fees from BioMarin, Nutricia, Vitaflo, Sanofi, Takeda, Recordati, and travel support from Vitaflo. SEC received consulting payments and speaker fees from BioMarin as well as consulting payments from Synlogic Therapeutics. COH was clinical trial investigator for BioMarin and received consulting and speaker payments from BioMarin. SCJH received consulting payments and travel support from BioMarin and Homology Medicines. NL received consulting payments from Alnylam, Amicus, Astellas, BioMarin, BridgeBio, Chiesi, Genzyme/Sanofi, HemoShear, Horizon Therapeutics, Jaguar, Moderna, Nestle, PTC Therapeutics, Reneo, Shire, Synlogic, and Ultragenyx, participated as clinical trial investigator for Aeglea, Amicus, Astellas, BioMarin, Genzyme/Sanofi, Homology, Horizon, Moderna, Pfizer, Protalix, PTC Therapeutics, Reneo, Retrophin/Travere therapeutics, Shire, and Ultragenyx, as well as received speaker fees from Cycle Pharmaceuticals, Leadiant and Recordati. MCM II received consulting payments from BioMarin, Horizon Therapeutics, Rhythm Pharmaceuticals, Applied Therapeutics, Cycle Therapeutics, and Ultragenyx. ALSP received speaker fees from BioMarin. JCR received consulting payments from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, and Nutricia, speaker fees from Applied Pharma Research, Merck Serono, BioMarin Pharmaceutical, Vitaflo, Cambrooke, PIAM, LifeDiet, and Nutricia, as well as travel support from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, Cambrooke, PIAM, and Nutricia. SS received consulting payments, research grants, speaker fees, and travel support from BioMarin and participated as clinical trials investigator for BioMarin. ASV received consulting payments from BioMarin, Horizon Therapeutics, and Ultragenyx and participated as clinical trial investigator for Acadia, Alexion, BioMarin, Genzyme, Homology Medicines, Kaleido, Mallinckrodt, and Ultragenyx. JV received consulting payments from BioMarin, LogicBio Pharmaceuticals, Sangamo Therapeutics, Orphan Labs, Synlogic Therapeutics, Sanofi, Axcella Health, Agios Pharmaceuticals, and Applied Therapeutics as well as travel grants from BioMarin and LogicBio Pharmaceuticals. MW received consulting payments, speaker fees, and travel support from BioMarin, and participated as clinical trial investigator for Mallinckrodt, Roche, Wave, Cycle Therapeutics, and Intrabio. ACM participated in strategic advisory boards and received honoraria as a consultant and as a speaker for Merck Serono, BioMarin, Nestlé Health Science (SHS), Applied Pharma Research, Actelion, Retrophin, Censa, PTC Therapeutics, and Arla Food. Publisher Copyright: © 2022 The AuthorsBackground: Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited. Methods: Two meetings were held with a multidisciplinary international panel of 25 experts in PKU and comorbidities frequently experienced by patients with PKU. Based on the outcomes of the first meeting, a set of statements were developed. During the second meeting, these statements were voted on for consensus generation (≥70% agreement), using a modified Delphi approach. Results: A total of 37 consensus recommendations were developed across five areas that were deemed important in the management of adolescents and young adults with PKU: (1) general physical health, (2) mental health and neurocognitive functioning, (3) blood Phe target range, (4) PKU-specific challenges, and (5) transition to adult care. The consensus recommendations reflect the personal opinions and experiences from the participating experts supported with evidence when available. Overall, clinicians managing adolescents and young adults with PKU should be aware of the wide variety of PKU-associated comorbidities, initiating screening at an early age. In addition, management of adolescents/young adults should be a joint effort between the patient, clinical center, and parents/caregivers supporting adolescents with gradually gaining independent control of their disease during the transition to adulthood. Conclusions: A multidisciplinary international group of experts used a modified Delphi approach to develop a set of consensus recommendations with the aim of providing guidance and offering tools to clinics to aid with supporting adolescents and young adults with PKU.publishersversionpublishe

    An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study

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    Screenwide is a case-control study (2017-2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers

    Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

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    Background The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. Methods Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case–control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. Findings Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples. Funding This study was funded by a competitive grant from Instituto de Salud Carlos III through the projects PI19/01835, PI23/00790, and FI20/00031, CIBERESP CB06/02/0073 and CIBERONC CB16/12/00231, CB16/12/00234 (Co-funded by European Regional Development Fund. ERDF: A way to build Europe). Samples and data were provided by Biobank HUB-ICO-IDIBELL, integrated into the Spanish Biobank Network, and funded by the Instituto de Salud Carlos III (PT20/00171) and by Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d’Oncologia de Catalunya. This work was supported in part by the AECC, Grupos estables (GCTRA18014MATI). It also counts with the support of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya, and grants to support the activities of research groups 2021SGR01354 and 2021SGR1112
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