Etiopathogenesis of ovarian cancer. An inflamm-aging entity?

Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate. The risk/protective factors of ovarian cancer suggest that its etiology is multifactorial. Several factors are involved in age-related increases in carcinogenesis, including the accumulation of senescent cells, inflammaging (a chronic inflammatory state that persists in the elderly), and immunosenescence (aging of the immune system) changes associated with poor immune surveillance. At sites of inflammation, exposure to high levels of inflammatory mediators, such as reactive oxygen species, cytokines, prostaglandins, and growth factors, contributes to increased cell division and genetic and epigenetic changes. These exposure-induced changes promote excessive cell proliferation, increased survival, malignant transformation, and cancer development. Furthermore, the proinflammatory tumor microenvironment contributes to ovarian cancer metastasis and chemoresistance. This narrative review of the literature was carried out to delineate the possible role of inflammaging in the etiopathogenesis of ovarian cancer development. We discuss the current carcinogenic hypotheses, sites of origin, and etiological factors of ovarian cancer. Treatment of inflammation may represent an attractive strategy for both the prevention and therapy of ovarian cancer. © 2022 The Author(s

Metal partitioning and speciation in a mining-impacted estuary by traditional and passive sampling methods

This study deals with the metal partitioning and bioavailability of metal/loids in the estuary Ria of Huelva (SW Spain) which is strongly affected by historical mining and industrial activities. To address this issue, traditional (i.e., grab samples) and passive sampling (i.e., diffusive gradient in thin films, DGTs) was carried out in the outer part of the estuary during different tidal cycles in order to determine the dissolved and particulate metal/loid concentrations. The dissolved concentrations exceeded, by several orders of magnitude, those reported in other estuaries worldwide that are affected by anthropogenic activities. A spatial pattern was observed in the metal distribution; a decrease seaward was recorded for some of the elements associated with mining (e.g., Cu, Zn, and Cd), the opposite tendency is observed for others associated with harbor emissions (e.g., Sn, Ni, or Pb). A different metal/loid partitioning pattern was also observed; Fe, and to a lesser extent Pb and Sn, were chiefly found in the particulate matter, while the rest of the elements were mainly found in the dissolved form. The bioavailability of the metal/loids was studied by speciation using both geochemical modeling and DGTs; while concentrations in DGTs supported metal/loid speciation for Zn, Cd, Mn, Co, As, and Sb according to their affinity to form strong or weak complexes, some discrepancies were observed for other elements such as Cu, V, Fe, and Pb, which are prone to forming strong complexes. The main reason behind the unexpectedly high Fe and Pb DGTs concentrations may be associated with their presence in the colloidal particles passing through the DGT. There was a strong positive correlation between dissolved and DGT concentrations for Cd and Mn, and to a lesser extent for Fe and Cu, highlighting the direct relationship between the concentrations in water and availability to living organisms in the estuary.This work was supported by the Spanish Ministry of Economy and Competitiveness through the research project CAPOTE (CGL2017-86050-R) and by the CEIMAR Excellence Research Campus through the project CEIMAR-CEIJ-005. M.D. Basallote thanks the Spanish Ministry of Science and Innovation for the Postdoctoral Fellowship granted under application reference IJC2018-035056-I. The authors would also like to thank to the Co Editor-in-Chief Dr. Damiá Barceló and two anonymous reviewers for the support and comments that notably improved the quality of the original paper.Departamento de Geologí

Spanish Menopause Society position statement: use of tibolone in postmenopausal women

Tibolone is a drug with complex tissue-specific action that exhibits a combination of estrogenic, progestogenic, and slight androgenic activity. Its variable profile explains its clinical effects, depending on the target tissue where it is metabolized, its metabolites’ affinity for and potency in hormone receptors, and probable enzymatic activity modulation. In recent reviews and clinical trials, the effectiveness of tibolone in alleviating different hot flush menopause symptoms, mainly in mood and sexuality disorders, has been noted. In Spain, tibolone is the most prescribed hormonal treatment, and one of the most common complaints among postmenopausal women is change in sexual drive. For such reason, a panel of experts from the Spanish Menopause Society met to develop usage recommendations based on the best evidence available

What do TSECs provide in the menopausal hormone therapy?

Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45mg/BZA 20mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women

Perfil genético asociado a pacientes con síndrome aórtico agudo complicado: el estudio GEN-AOR

[EN] Introduction and objectives: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. Methods: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. Results: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. Conclusions: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. ClinicalTrials.gov (Identifier: NCT04751058)[ES] Introducción y objetivos: El papel de la genética en el diagnóstico y la personalización de los tratamientos de las aortopatías, es cada vez mayor. En este estudio se analizó la prevalencia de variantes genéticas en pacientes con síndrome aórtico agudo (SAA) admitidos consecutivamente en una unidad de cuidados intensivos y se evaluó su utilidad clínica. Métodos: Mediante secuenciación masiva, se analizó 42 genes asociados a aortopatías en pacientes con SAA no sindrómico. Las variantes identificadas se segregaron mediante secuenciación Sanger en los familiares disponibles. Además, se estudió la relación entre los resultados genéticos y algunas características clínicas mediante la aplicación de los test exactos de Fisher y de Fisher-Freeman-Halton. Resultados: El análisis de los datos genómicos de 73 pacientes de SAA dio como resultado la identificación de 34 variantes candidatas en 32 individuos, localizadas en 14 genes diferentes. La segregación familiar se realizó en 31 individuos pertenecientes a 9 familias, donde se encontraron 13 portadores de los que 10 mostraron un genotipo compatible con SAA. El estudio estadístico indicó que la ausencia de hipertensión, una menor edad, una historia familiar de SAA y la ausencia de dolor están asociadas con un estudio genético positivo. Conclusiones: Se amplió el espectro mutacional asociado a SAA. Además, tanto los pacientes índice como los familiares estudiados se han visto beneficiados por estos resultados, por lo que se puede establecer el protocolo de seguimiento adecuado para cada uno de ellos. Por último, es importante destacar la posibilidad de utilizar variables clínicas estadísticamente significativas como factores predictores del carácter hereditario del SAA. ClinicalTrials.gov (Identifier: NCT04751058)Este trabajo contó con el apoyo del Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad de España y fue cofinanciado por la Unión Europea (FEDER, «Una manera de hacer Europa ») [PI18-00612; PI19/01550; PI21-00244; IMP/00009], Consejería Regional de Salud y Familias del Gobierno Autónomo de Andalucía [PEER-0501-2019; PEER-0470-2019], Consejería Regional de Transformación Económica, Industria, Conocimiento y Universidades de Andalucía [P20_00887] y la Fundación Isabel.Peer reviewe

Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration

Can widely available measures of atrophy on magnetic resonance imaging increase diagnostic certainty of underlying frontotemporal lobar degeneration (FTLD) and estimate clinical deterioration in the behavioral variant of frontotemporal dementia (bvFTD)? This diagnostic/prognostic study investigated the clinical utility of 5 validated visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index. When combined, VAS showed excellent diagnostic performance for differentiating between bvFTD with high and low confidence of FTLD and for the estimation of longitudinal clinical deterioration, whereas the Magnetic Resonance Parkinsonism Index was increased in bvFTD with underlying 4-repeat tauopathies. These findings suggest that, in bvFTD, VAS can be used to increase diagnostic certainty of underlying FTLD and estimate longitudinal clinical deterioration. This diagnostic/prognostic study assesses the utility of 6 visual atrophy scales and the Magnetic Resonance Parkinsonism Index in patients with behavioral variant frontotemporal dementia to distinguish those with high vs low confidence of frontotemporal lobar degeneration. The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration

Patients receiving a high burden of antibiotics in the community in Spain: a cross-sectional study.

Some patients in the community receive a high burden of antibiotics. We aimed at describing the characteristics of these patients, antibiotics used, and conditions for which they received antibiotics. We carried out a cross-sectional study. Setting: Thirty Health Primary Care Areas from 12 regions in Spain, covering 5,960,191 inhabitants. Patients having at least 30 packages of antibacterials for systemic use dispensed in 2017 were considered. Main outcome measures: Prevalence of antibiotic use, conditions for which antibiotics were prescribed, clinical characteristics of patients, comorbidities, concomitant treatments, and microbiological isolates. Patient's average age was 70 years; 52% were men; 60% smokers/ex-smokers; 54% obese. Overall, 93% of patients had, at least, one chronic condition, and four comorbidities on average. Most common comorbidities were cardiovascular and/or hypertension (67%), respiratory diseases (62%), neurological/mental conditions (32%), diabetes (23%), and urological diseases (21%); 29% were immunosuppressed, 10% were dead at the time of data collection. Patients received three antibiotic treatments per year, mainly fluoroquinolones (28%), macrolides (21%), penicillins (19%), or cephalosporins (12%). Most frequently treated conditions were lower respiratory tract (infections or prophylaxis) (48%), urinary (27%), and skin/soft tissue infections (11%). Thirty-five percent have been guided by a microbiological diagnosis, being Pseudomonas aeruginosa (30%) and Escherichia coli (16%) the most frequent isolates. In conclusion, high antibiotic consumers in the community were basically elder, with multimorbidity and polymedication. They frequently received broad-spectrum antibiotics for long periods of time. The approach to infections in high consumers should be differentiated from healthy patients receiving antibiotics occasionally

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe