Influencia del tratamiento prequirúrgico de la acromegalia con análogos de somatostatina

[Resumen] Contexto: La cirugía transesfenoidal es el tratamiento de primera línea de la acromegalia aceptado en la mayoría de los pacientes. Los resultados de estudios previos referentes al tratamiento preoperatorio con análogos de somatostatina y las tasas de curación quirúrgica son contradictorios, encontrando beneficio en algunos y ninguna diferencia en otros. Objetivo: El objetivo de este trabajo, basado en un meta-análisis de todos los estudios publicados, es investigar si el tratamiento prequirúrgico con análogos de somatostatina mejora el resultado quirúrgico de la acromegalia. Fuentes de datos: Se realizó una revisión sistemática de todos los estudios de tratamiento prequirúrgico de acromegalia con análogos de somatostatina hasta Diciembre de 2011. Se revisaron las bases de datos electrónicas Medline, Embase, Cochrane y Google Scholar. El objetivo primario fue la tasa de curación bioquímica. Se identificaron 286 estudios, seleccionando 10 de ellos (3.49%) por cumplir los requisitos para el análisis; 5 estudios retrospectivos con grupo control, 2 ensayos prospectivos no aleatorizados y 3 ensayos prospectivos controlados. El meta-análisis se realizó empleando el modelo de efectos aleatorios. Extracción de datos: La extracción de datos de los estudios se realizó por dos observadores independientes. Síntesis de datos: Se detectó un efecto límite en el análisis global de todos los estudios, con una odds ratio (OR) para curación bioquímica con tratamiento prequirúrgico de 1.62 (95% IC, 0.93-2.82). En el análisis de los tres ensayos prospectivos controlados, se identificó un efecto estadísticamente significativo con una OR de 2.58 (95% CI, 1.14-5.80). Conclusión: El tratamiento prequirúrgico de adenomas hipofisarios productores de GH con análogos de somatostatina produce una mejoría significativa en el resultado quirúrgico, analizando además la importancia del tratamiento prequirúrgico en centros sin resultados quirúrgicos óptimos.[Resumo] Contexto: A cirurxía transesfenoidal é o tratamento de primeira liña da acromegalia aceptado na maioría dos pacientes. Os resultados de estudos previos referentes ao tratamento preoperatorio con análogos de somatostatina e as taxas de curación quirúrgica son contradictorios, atopando beneficio nalgúns e ningunha diferenza noutros. Obxectivo: O obxectivo deste traballo, baseado nun meta-análise de todos os estudos publicados, é investigar si o tratamento precirúrxico con análogos de somatostatina mellora o resultado cirúrxico da acromegalia. Fontes de datos: Realizouse unha revisión sistemática de todos os estudos de tratamento precirúrxico de acromegalia con análogos de somatostatina ata Decembro de 2011. Revisáronse as bases de datos electrónicas Medline, Embase, Cochrane e Google Scholar. O obxectivo primario foi a taxa de curación bioquímica. Identificáronse 286 estudos, seleccionando 10 deles (3.49%) por cumprir os requisitos para a análise; 5 estudos retrospectivos con grupo control, 2 ensaios prospectivos non aleatorizados e 3 ensaios prospectivos controlados. O meta-análise realizouse empregando o modelo de efectos aleatorios. Extracción de datos: A extracción de datos dos estudos realizouse por dous observadores independentes. Síntese de datos: Detectouse un efecto límite na análise global de todos os estudos, cunha odds ratio (OR) para curación bioquímica con tratamento precirúrxico de 1.62 (95% IC, 0.93-2.82). Na análise dos tres ensaios prospectivos controlados, identificouse un efecto estadísticamente significativo cunha OR de 2.58 (95% CI, 1.14-5.80). Conclusión: O tratamento precirúrxico de adenomas hipofisarios productores de GH con análogos de somatostatina produce unha melloría significativa no resultado cirúrxico, analizando ademáis a importancia do tratamento precirúrxico en centros sen resultados cirúrxicos óptimos.[Abstract] Context: Transsphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA) treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences. Objective: The aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly. Data Sources: All studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. Study Selection: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49%) fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model. Data Extraction: Data were extracted from published reports by two independent observers. Data Synthesis: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR) for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93-2.82). In the analysis of the four prospective controlled trials, a statistically significant effect was identified OR: 2.58 (95% CI, 1.14-5.80) Conclusions: Preoperative treatment with SSA of GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis strongly suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment

Cost-effectiveness analysis of preoperative treatment of acromegaly with somatostatin analogue on surgical outcome

[Abstract] Context. There is no uniform standard of care for acromegaly. Due to the high costs involved, steps must be taken to ensure the cost-effective delivery of treatment. Objective. Taking the results of an earlier meta-analysis as a starting point, this study aims to determine whether treatment with long-acting somatostatin analogue (SSA) prior to surgery improves the cost-effectiveness of the treatment of acromegaly. Methods. The results are presented as an Incremental Cost Effectiveness Ratio (ICER) immediately after surgery, for the following year and over the next four decades. The cure rates percentage (95% CI) for the three randomized prospective controlled trials were 44.4% (34.2–54.7) and 18.2% (10.1–26.3) for preoperative treated and untreated patients respectively. The cost of pharmacological treatments was based on the number of units prescribed, dose and length of treatment. Results. The mean (95% CI) ICER immediately after surgery was €17,548 (12,007–33,250). In terms of the postoperative SSA treatment, the ICER changes from positive to negative before two years after surgery. One decade after surgery the ICER per patient/year was €− 9973 (− 18,798; − 6752) for postoperative SSA treatment and €− 31,733 (− 59,812; − 21,483) in the case of postoperative pegvisomant treatment. Conclusions. In centres without optimal surgical results, preoperative treatment of GH-secreting pituitary macroadenomas with SSA not only shows a significant improvement in the surgical results, but is also highly cost-effective, with an ICER per patient/year one decade after surgery, of between €− 9973 (− 18,798; − 6752) and €− 31,733 (− 59,812; − 21,483) for SSA and pegvisomant respectively.Instituto de Salud Carlos III; PI10/00088Instituto de Salud Carlos III; PI13/00322Xunta de Galicia; IN845B-2010/187Xunta de Galicia; 10CSA916014PRXunta de Galicia; CN2012/31

Dinámica de septinas y regulación de la separación celular durante el crecimiento hifal de Candida albicans ¿una diana de antifúngicos?

Resumen del trabajo presentado al "IV Congreso GEBMP: Simposio Hongos Patógenos" celebrado en Badajoz el 6 de julio del 2012.Peer Reviewe

Concordance among methods of nutritional assessment in patients included on the waiting list for liver transplantation

[Abstract] Background: The aim of the present study was to determine the extent of malnutrition in patients waiting for a liver transplant. The agreement among the methods of nutritional assessment and their diagnostic validity were evaluated. Methods: Patients on the waiting list for liver transplantation (n = 110) were studied. The variables were: body mass index, analytical parameters, liver disease etiology, and complications. Liver dysfunction was evaluated using the Child-Pugh Scale. Nutritional state was studied using the Controlling Nutritional Status (CONUT), the Spanish Society of Parenteral and Enteral Nutrition (SENPE) criteria, the Nutritional Risk Index (NRI), the Prognostic Nutritional Index (PNI-O), and the Subjective Global Assessment (SGA). Agreement was determined using the Kappa index. Area under receiver operator characteristic curves (AUCs), the Youden index (J), and likelihood ratios were computed. Results: Malnutrition varied depending on the method of evaluation. The highest value was detected using the CONUT (90.9%) and the lowest using the SGA (50.9%). The pairwise agreement among the methods ranged from K = 0.041 to K = 0.826, with an overall agreement of each criteria with the remaining methods between K = 0.093 and K = 0.364. PNI-O was the method with the highest overall agreement. Taking this level of agreement into account, we chose the PNI-O as a benchmark method of comparison. The highest positive likelihood ratio for the diagnosis of malnutrition was obtained from the Nutritional Risk Index (13.56). Conclusions: Malnutrition prevalence is high and prevalence estimates vary according the method used, with low concordance among methods. PNI-O and NRI are the most consistent methods to identify malnutrition in these patients.Instituto de Salud Carlos III; PI11/012

A membrane-associated form of the transcription factor Ace2 controls septin ring dynamics during Candida albicans hyphal growth

Resumen del trabajo presentado a la Vth International Conference on Molecular Mechanisms of Fungal Cell Wall Biogenesis celebrada en Primosten (Croacia) del 6 al 9 de Junio de 2012.Peer Reviewe

Valor pronóstico del índice de riesgo nutricional en receptores de trasplante cardiaco

[Abstract] Introduction and objectives. To study the prognostic impact of preoperative nutritional status, as assessed through the nutritional risk index (NRI), on postoperative outcomes after heart transplantation (HT). Methods. We conducted a retrospective, single-center study of 574 patients who underwent HT from 1991 to 2014. Preoperative NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (body weight [kg] / ideal body weight [kg]). The association between preoperative NRI and postoperative outcomes was analyzed by means of multivariable logistic regression and multivariable Cox regression. Results. Mean NRI before HT was 100.9 ± 9.9. According to this parameter, the prevalence of severe nutritional risk (NRI < 83.5), moderate nutritional risk (83.5 ≤ NRI < 97.5), and mild nutritional risk (97.5 ≤ NRI < 100) was 5%, 22%, and 10%, respectively. One year post-transplant mortality rates in these 4 categories were 18.2%, 25.3%, 7.9% and 10.2% (P < .001), respectively. The NRI was independently associated with a lower risk of postoperative infection (adjusted OR, 0.97; 95%CI, 0.95-1.00; P = .027) and prolonged postoperative ventilator support (adjusted OR, 0.96; 95%CI, 0.94-0.98; P = .001). Patients at moderate or severe nutritional risk had significantly higher 1-year post-HT mortality (adjusted HR, 1.55; 95%CI, 1.22-1.97; P < .001). Conclusions. Malnourished patients have a higher risk of postoperative complications and mortality after HT. Preoperative NRI determination may help to identify HT candidates who might benefit from nutritional intervention.[Resumen] Introducción y objetivos. Analizar el impacto del estado nutricional preoperatorio, evaluado mediante el índice de riesgo nutricional (IRN), en el pronóstico tras el trasplante cardiaco (TxC). Métodos. Se realizó un estudio retrospectivo de 574 pacientes que recibieron un TxC entre 1991 y 2014 en un centro. El IRN preoperatorio se calculó como 1,519 × albúmina (g/l) + 41,7 × (peso real [kg] / peso ideal [kg]). La asociación entre IRN preoperatorio y eventos clínicos posoperatorios se analizó mediante modelos multivariables de regresión logística y regresión de Cox. Resultados. El IRN preoperatorio medio de la población del estudio era de 100,9 ± 9,9. Según este parámetro, las prevalencias de riesgo nutricional grave (IRN < 83,5), moderado (83,5 ≤ IRN < 97,5) y leve (97,5 ≤ IRN < 100) antes del TxC eran el 5, el 22 y el 10% respectivamente. Las tasas de mortalidad a 1 año tras el TxC en estas 4 categorías fueron del 18,2, el 25,3, el 7,9 y el 10,2% (p < 0,001) respectivamente. El IRN preoperatorio resultó predictor independiente de menor riesgo de infección posoperatoria (odds ratio ajustada [ORa] = 0,97; intervalo de confianza del 95% [IC95%], 0,95-1,00; p = 0,027) y ventilación mecánica prolongada posoperatoria (ORa = 0,96; IC95%, 0,94-0,98; p = 0,001). Los pacientes con riesgo nutricional moderado a grave mostraron mayor mortalidad a 1 año tras el TxC (hazard ratio ajustada = 1,55; IC95%, 1,22-1,97; p < 0,001). Conclusiones. Los pacientes desnutridos tienen mayor riesgo de complicaciones posoperatorias y muerte tras el TxC. La determinación del IRN podría facilitar la identificación de candidatos a TxC que se beneficien de intervenciones nutricionales en espera del órgano

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and human patients’ studies are supported by an ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019 of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. SCLl is supported by MINECO/FEDER research grants (RTI2018-094130-B-100). CH was supported by the Department of Defense (DoD) BCRP, No. BC190820; and the National Cancer Institute (NCI) at the National Institutes of Health (NIH), No. R01CA184476. Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D +i, 2017–2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the “la Caixa” Banking Foundation under the project code HR18-00304 and a Severo Ochoa CNIC Intramural Project (Exp. 12-2016 IGP) to J.J.S

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

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