Identificació i difusió de la producció científica de l’Hospital Universitari de Tarragona Joan XXIII: les bibliotecàries prenem la iniciativa

Visibilitat; Producció científica; Biblioteca 2.0Visibilidad; Producción científica; Biblioteca 2.0Visibility; Scientific production; Library 2.0Introducció L’any 2013, després de conèixer les actuacions d’altres biblioteques en la difusió de la producció científica pròpia, les bibliotecàries de l’Hospital Universitari de Tarragona Joan XXIII (d’ara endavant, HJ23) veiem l’oportunitat d’iniciar un nou servei a la nostra institució: la identificació i difusió de la producció científica de l’HJ23. Metodologia Per detectar la producció científica elaborem una estratègia de cerca, tenint en compte totes les variants del nom de la nostra institució utilitzades pels autors. Adaptem l’estratègia per a Pubmed, Scopus i Google Acadèmic, per tal de localitzar el màxim de publicacions sota el nom de l’HJ23, activant les alertes en cada base de dades per poder‐ne fer el seguiment. Introduïm les dades bibliogràfiques verificades de cada document al gestor bibliogràfic. A partir d’aquí, fem la difusió periòdicament de la nostra producció científica mitançant el butlletí de la Biblioteca, l’InfoBiblio. Paral∙lelament i des de l’any 2016, elaborem els tuits de cada publicació científica, afegint l’etiqueta #hjoan23publica, així com d’altres etiquetes que millorin la visibilitat de la nostra investigació. Aquests tuits es publiquen des del compte institucional de Twitter @hjoan23. L’any 2018 iniciem l’arxiu digital dels articles que tenen filiació institucional. Això ho fem mitjançant el nostre Servei d’Obtenció de Documents. Resultats Des que vam començar hem identificat més de 400 publicacions amb filiació HJ23, tots ells s’han publicat a l’InfoBiblio, s’han elaborat tuits perquè siguin publicats des del compte @hjoan23 al Twitter, i des del 2018 aquestes publicacions s’han recopilat i arxivat a text complet. Conclusions La nostra aportació millora tant la identificació i arxiu com la visibilitat de la investigació que es fa des de l’HJ23, així com també la normalització del nom de filiació de la nostra institució, que es fa conjuntament amb la direcció de l’Hospital. El futur de la identificació i difusió de la producció científica de l’HJ23 passa per la seva incorporació al repositori institucional Scientia que n’afavoreix l’accessibilitat, la visibilitat, l’impacte i el reconeixement

The wide spectrum of POT1 gene mutations correlates with multiple cancer types.

The POT1 protein forms part of the shelterin complex, which binds and protects telomeres. Germline mutations in the POT1 gene have recently been shown to be involved in tumors in different tissues such as familial colorectal, glioma and melanoma tumors, which demonstrate the importance of this gene. Recently, we uncovered a mutation in the POT1 gene (p.R117C) as causative of cardiac angiosarcomas in families with multiple tumors. Our in silico studies predicted that the POT1 p.R117C protein had lost the ability to interact with TPP1 and ssDNA. In vitro studies corroborated this prediction, and showed that this lack of function leads to abnormally long telomeres with increased fragility. In order to better understand the spectrum of mutations in the POT1 gene and its relation with tumorigenesis, we extended the study to families with multiple tumors (with and without angiosarcomas) and sporadic angiosarcomas and cardiac sarcomas. We found four new mutations that were not described previously and another patient carrying the previously described p.R117C mutation. In silico studies predicted that these new mutations were damaging in the same manner as previously described for the POT1 p.R117C mutation. These mutations were present in both, families and sporadic cases with angiosarcomas and sarcomas, although the major part was involved in families with AS and in cardiac tumors. The wide spectrum of mutations in the POT1 gene leading to different tumorigenesis processes demonstrates the general importance of this gene.pre-print252 K

IL-6 Trans-Signaling in the Brain Influences the Metabolic Phenotype of the 3xTg-AD Mouse Model of Alzheimer's Disease

Altres ajuts: Fundació La Marató de TV3 (20142210)Alzheimer's disease (AD) is a neurodegenerative disorder that causes the most prevalent dementia in the elderly people. Obesity and insulin resistance, which may cause major health problems per se, are risk factors for AD, and cytokines such as interleukin-6 (IL-6) have a role in these conditions. IL-6 can signal either through a membrane receptor or by trans-signaling, which can be inhibited by the soluble form of the co-receptor gp130 (sgp130). We have addressed the possibility that blocking IL-6 trans-signaling in the brain could have an effect in the triple transgenic 3xTg-AD mouse model of AD and/or in obesity progression, by crossing 3xTg-AD mice with GFAP-sgp130Fc mice. To serve as control groups, GFAP-sgp130Fc mice were also crossed with C57BL/6JOlaHsd mice. Seventeen-month-old mice were fed a control diet (18% kcal from fat) and a high-fat diet (HFD; 58.4% kcal from fat). In our experimental conditions, the 3xTg-AD model showed a mild amyloid phenotype, which nevertheless altered the control of body weight and related endocrine and metabolic factors, suggestive of a hypermetabolic state. The inhibition of IL-6 trans-signaling modulated some of these traits in both 3xTg-AD and control mice, particularly during HFD, and in a sex-dependent manner. These experiments provide evidence of IL-6 trans-signaling playing a role in the CNS of a mouse model of AD

Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia

The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to MSH2 alterations. LS was confirmed in 68 patients, 53 with MSH2 mutations and 15 with EPCAM 3'-end deletions. Tissue microarrays were constructed with human normal tissues and their malignant counterparts to assist in the evaluation of EPCAM staining. Among 154 MSH2-negative lesions, 17 were EPCAM-negative, including 10 CRC and 7 colorectal polyps, and 5 of them showed only isolated negative glands. All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3'-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3'-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps

SEOM clinical guidelines in hereditary breast and ovarian cancer (2019)

Mutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers

El cáncer hereditario en mujeres

Most cases of cancer are sporadic, whereas 5-10% are hereditary and about 20-30% of cancers tend to cluster in families. Families and individuals who are suspected of suffering from hereditary cancer need to undergo a process known as genetic counseling, which is of considerable importance in the prevention and early detection of malignant tumours. The most common hereditary cancer syndromes are: hereditary breast-ovarian cancer syndrome, familial adenomatous polyposis and Lynch syndrome. Genetic diagnosis allows clinicians to estimate the risks of developing different cancers in order to make decisions over surveillance and prophylactic surgery to reduce these risks. The ultimate goal is to reduce cancer mortality through early diagnosis and prevention.La mayoría de los casos de cáncer son esporádicos, entre un 20-30% presentan agregación familiar, mientras que solo el 5 -10% son de carácter hereditario. Las familias e individuos en los que se sospecha que padecen cáncer hereditario deben someterse a un proceso de asesoramiento genético, que es de gran importancia para la prevención y detección temprana de tumores malignos. Los síndromes más frecuentes de cáncer hereditario son el síndrome de mama-ovario hereditario, la poliposis adenomatosa familiar y el síndrome de Lynch. El diagnóstico genético facilita realizar una estimación de los riesgos de desarrollar diferentes cánceres, permitiendo tomar decisiones de vigilancia y preventivas que reducen estos riesgos. El objetivo final es reducir la mortalidad por cáncer mediante el diagnóstico precoz y la prevención

Hereditary Cancer In Women

[spa] La mayoría de los casos de cáncer son esporádicos, entre un 20-30% presentan agregación familiar, mientras que solo el 5 -10% son de carácter hereditario. Las familias e individuos en los que se sospecha que padecen cáncer hereditario deben someterse a un proceso de asesoramiento genético, que es de gran importancia para la prevención y detección temprana de tumores malignos. Los síndromes más frecuentes de cáncer hereditario son el síndrome de mama-ovario hereditario, la poliposis adenomatosa familiar y el síndrome de Lynch. El diagnóstico genético facilita realizar una estimación de los riesgos de desarrollar diferentes cánceres, permitiendo tomar decisiones de vigilancia y preventivas que reducen estos riesgos. El objetivo final es reducir la mortalidad por cáncer mediante el diagnóstico precoz y la prevención.[eng] Most cases of cancer are sporadic, whereas 5-10% are hereditary and about 20-30% of cancers tend to cluster in families. Families and individuals who are suspected of suffering from hereditary cancer need to undergo a process known as genetic counseling, which is of considerable importance in the prevention and early detection of malignant tumours. The most common hereditary cancer syndromes are: hereditary breast-ovarian cancer syndrome, familial adenomatous polyposis and Lynch syndrome. Genetic diagnosis allows clinicians to estimate the risks of developing different cancers in order to make decisions over surveillance and prophylactic surgery to reduce these risks. The ultimate goal is to reduce cancer mortality through early diagnosis and prevention

Mammographic density and breast cancer in women from high risk families

Introduction: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype. Methods: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype. Results: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes. Conclusions: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization

Simple Summary Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancer (RCC), with no data on its prevalence worldwide. No genotype-phenotype associations have been described. The aim of our study was to describe the genotypic and phenotypic features of the largest series of patients with HLRCC from Spain reported to date. Of 27 FH germline pathogenic variants, 12 were not previously reported in databases. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants. The frequency of RCCs (10.9%) was lower than those reported in the previously published series. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk