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1.
Nat Commun ; 15(1): 3593, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678021

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease for which better therapies are urgently needed. Fibroblasts and macrophages are heterogeneous cell populations able to enhance metastasis, but the role of a macrophage-fibroblast crosstalk in regulating their pro-metastatic functions remains poorly understood. Here we deconvolve how macrophages regulate metastasis-associated fibroblast (MAF) heterogeneity in the liver. We identify three functionally distinct MAF populations, among which the generation of pro-metastatic and immunoregulatory myofibroblastic-MAFs (myMAFs) critically depends on macrophages. Mechanistically, myMAFs are induced through a STAT3-dependent mechanism driven by macrophage-derived progranulin and cancer cell-secreted leukaemia inhibitory factor (LIF). In a reciprocal manner, myMAF secreted osteopontin promotes an immunosuppressive macrophage phenotype resulting in the inhibition of cytotoxic T cell functions. Pharmacological blockade of STAT3 or myMAF-specific genetic depletion of STAT3 restores an anti-tumour immune response and reduces metastases. Our findings provide molecular insights into the complex macrophage-fibroblast interactions in tumours and reveal potential targets to inhibit PDAC liver metastasis.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Macrófagos , Neoplasias Pancreáticas , Fator de Transcrição STAT3 , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Animais , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Macrófagos/metabolismo , Macrófagos/imunologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Humanos , Camundongos , Linhagem Celular Tumoral , Transdução de Sinais , Janus Quinases/metabolismo , Camundongos Endogâmicos C57BL , Fibroblastos/metabolismo , Fibroblastos/patologia , Masculino , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Feminino
2.
Transl Pediatr ; 12(11): 1971-1980, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38130580

RESUMO

Background: Neutrophil-to-lymphocyte ratio (NLR) has been recently postulated as an inflammatory biomarker for the diagnosis of vesicoureteral reflux (VUR). The aim of this study is to determine the role of NLR as a predictor of evolution of primary VUR in patients with associated acute pyelonephritis (APN). Methods: A retrospective observational cohort study was performed in patients with APN episodes with associated primary VUR diagnosed between 2013-2020. Patients were divided into two groups according to VUR evolution after APN: group A [spontaneous resolution (SR)] and group B [VUR complications development (CD) during follow-up: new APN or renal function worsening]. Demographic, prenatal, laboratory, microbiological and radiological data were analysed. Sensitivity and specificity for CD of VUR was determined by receiver operating characteristic (ROC) curves. Results: A total of 1,146 episodes of APN were analysed of which 273 patients with APN and associated primary VUR were finally included (median age of 11 months at APN diagnosis). SR of VUR occurred in 169 patients (SR group), while CD were observed in the remaining 104 patients (CD group). No differences in demographic, prenatal, microbiological and radiological features were observed. CD patients had significantly higher levels of leukocytes, neutrophils, NLR, C-reactive protein and creatinine. NLR was the parameter with the highest area under the curve (AUC =0.966) for predicting the development of VUR complications (cut-off point =3.41) with a maximum sensitivity of 92.7% and specificity of 91.1% (P<0.001). Conclusions: NLR may be considered as a simple and cost-effective predictor of clinical outcome of VUR, which may correlate with the increased risk of developing complications of primary VUR after an episode of APN. Therefore, it should be included in the management algorithm for these patients, although future prospective studies are still required to confirm these results.

3.
Genes (Basel) ; 14(10)2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37895227

RESUMO

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS.


Assuntos
Acidose , Hiperpotassemia , Hipertensão , Indapamida , Criança , Adulto , Humanos , Tiazidas , Proteína Quinase 1 Deficiente de Lisina WNK/genética
4.
Front Neurosci ; 17: 1200370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37694111

RESUMO

Surely, Vittorio Erspamer, discoverer of Enteramine in 1935, and Irvine Page, Maurice M. Rapport and Arda Green, discoverers of Serotonin in 1948, never imagined the biological importance that this fundamental molecule has in the living beings of our planet; from its physiological, passing through endocrine, neural, developmental and reproductive functions and even its role in evolution. For this reason, our workgroup is commemorating these researchers and celebrating their great discovery, which deeply influenced science and medicine, in the present perspective article. As a consequence of their seminal work, and the work of many other researchers in the field of serotonin over the following years, now we stand in front of the practical concept of "Serotoninomics," which we think will contribute to find out precise answers regarding basic, clinical, and translational research related to serotonin, just as the emerging medical and "omics" sciences have done before.

5.
Pediatr Transplant ; 27(7): e14589, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37543721

RESUMO

BACKGROUND: There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN-TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence-based protocols. METHODS: A cross-sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN-TransplantChild. RESULTS: A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on-site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%-100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2-4 weeks) for live-attenuated vaccines (LAVs). Almost all sites recommended immunization in the post-transplant period, with a time window of 4-8 months for the inactivated vaccines and 16-24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases. CONCLUSIONS: The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence-based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies.

6.
Cancer Cell ; 41(9): 1637-1649.e11, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37652007

RESUMO

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.


Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/genética , Encéfalo , Perfilação da Expressão Gênica , Aprendizado de Máquina , Mutação
7.
Int J Mol Sci ; 24(8)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37108589

RESUMO

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Qualidade de Vida , Reprodutibilidade dos Testes , Biomarcadores , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
9.
Pediatr Infect Dis J ; 42(6): 510-514, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36795569

RESUMO

BACKGROUND: Epidermolysis bullosa (EB) is frequently complicated by skin infection, which can lead to bacteremia. However, bloodstream infections (BSI) in patients with EB have not been well described. METHODS: Retrospective study of BSI in children 0-18 years with EB from a national reference unit in Spain, in 2015-2020. RESULTS: Among 126 children with EB, we identified 37 BSI episodes in 15 patients (14 recessive dystrophic EB, 1 junctional EB). The most frequent microorganisms were Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 11). Five P. aeruginosa isolates were ceftazidime-resistant (42%), 4 of which were also resistant to meropenem and quinolones (33%). As for S. aureus , 4 (36%) were methicillin-resistant and 3 (27%) clindamycin-resistant. In 25 (68%) BSI episodes skin cultures had been performed in the previous 2 months. The most frequent isolates were also P. aeruginosa (n = 15) and S. aureus (n = 11). In 13 cases (52%), smear and blood cultures grew the same microorganism, with the same antimicrobial resistance pattern in 9 isolates. Twelve patients (10%) died during follow-up (9 RDEB and 3 JEB). BSI was the cause of death in 1 case. In patients with severe RDEB, a history of BSI was associated with higher mortality (OR 6.1, 95% CI: 1.33-27.83, P = 0.0197). CONCLUSIONS: BSI is an important cause of morbidity in children with severe forms of EB. The most frequent microorganisms are P. aeruginosa and S. aureus , with high rates of antimicrobial resistance. Skin cultures can help guide treatment decisions in patients with EB and sepsis.


Assuntos
Anti-Infecciosos , Bacteriemia , Epidermólise Bolhosa , Humanos , Criança , Estudos Retrospectivos , Staphylococcus aureus , Epidermólise Bolhosa/complicações , Bacteriemia/epidemiologia , Bacteriemia/complicações , Pseudomonas aeruginosa
11.
Nefrologia (Engl Ed) ; 42 Suppl 2: 5-132, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36503720

RESUMO

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.


Assuntos
Falência Renal Crônica , Transplante de Rim , Insuficiência Renal Crônica , Humanos , Rim , Doadores Vivos , Falência Renal Crônica/cirurgia
12.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1535250

RESUMO

Objetivo: Describir los métodos anticonceptivos reportados por las usuarias de servicios de interrupción voluntaria del embarazo (IVE), antes y posterior a la consulta, y explorar la asociación entre las características sociodemográficas y los antecedentes ginecológicos con la elección de anticonceptivos de alta eficacia posterior a la IVE, con gestaciones menores de 15 semanas, en el departamento de Antioquia, Colombia, en la institución Profamilia, entre el 2015 y el 2020. Metodología: Estudio de corte transversal. Se analizaron los 13 067 registros de consultas de IVE realizadas en Profamilia de la regional Antioquia, del 2015 al 2020. Las variables cualitativas se midieron con frecuencias y porcentajes, y las cuantitativas, con la media y la desviación estándar. Se implementaron modelos de regresión logística para establecer la asociación de las variables independientes con la variable de interés. Resultados: La consulta de IVE contribuyó al incremento del uso de métodos anticonceptivos de alta eficacia. Antes de la IVE, el 53 % de las mujeres no usaban ningún método. Posterior a la interrupción, el 97 % empezó a utilizar métodos de alta eficacia. Además del uso de métodos poco eficaces o el uso de preservativo, obtuvieron una posibilidad 13 veces más alta de elegir un método de alta eficacia. Conclusiones: La educación en métodos anticonceptivos posterior a una IVE es fundamental para promover el uso de opciones muy efectivas, con el fin de disminuir la aparición de nuevos embarazos no deseados que puedan llevar a una IVE recurrente.


Objective: To describe the contraceptive methods reported by users of voluntary termination of pregnancy (VTP) services, before and after consultation, and to examine the association between sociodemographic characteristics and gynecological history with choosing highly effective contraceptive methods after VTP, in gestations shorter than 15 weeks, in the department of Antioquia, Colombia, at the Profamilia institution, from 2015 to 2020. Methodology: This is a cross-sectional study. We analyzed 13 067 records of VTP consultations performed in Profamilia in Antioquia from 2015 to 2020. Qualitative variables were measured with frequencies and percentages, and quantitative variables with the mean and standard deviation. Logistic regression models were implemented to establish the association of the independent variables with the variable of interest. Results: VTP consultation contributed to increased use of highly effective contraceptive methods. Before VTP, 53% of women were not using any method. After the termination, 97% started using highly effective methods. Likewise, those using low efficacy methods or condoms were 13 times more likely to choose a highly effective method. Conclusions: Post-VTP contraceptive education is essential for promoting the use of highly effective methods to reduce the occurrence of new unwanted pregnancies that may lead to repeated VTP


Objetivo: Descrever os métodos anticoncepcionais referidos pelas usuárias de serviços de interrupção voluntária da gravidez (IVG), antes e depois da consulta, e estudar a associação entre as características sociodemográficas e os antecedentes ginecológicos com a eleição de anticoncepcionais de alta eficiência depois da IVG, com gestações menores de 15 semanas, no departamento de Antioquia, Colômbia, na instituição Profamilia, entre 2015 e 2020. Metodologia: Estudo de corte transversal. Analisaram-se os 13067 registros de consultas de IVG realizadas em Profamilia na sede Antioquia, de 2015 a 2020. As variáveis qualitativas mediram-se com frequências e porcentagens, e as quantitativas com a média e o desvio padrão. Implementaram-se modelos de regressão logística para estabelecer a associação das variáveis independentes com a variável de interesse. Resultados: A consulta de IVG contribuiu ao incremento do uso de métodos anticoncepcionais de alta eficiência. Antes da IVG, o 53% das mulheres não usavam nenhum método. Depois da interrupção, o 97% começou a usar métodos de alta eficiência. Além do uso de métodos pouco eficientes ou o uso da camisinha, obtiveram uma possibilidade 13 vezes maior de escolher um método de alta eficiência. Conclusões: A educação em métodos anticoncepcionais posterior a uma IVG é fundamental para promover o uso de opções muito efetivas, com o fim de diminuir a aparição de novas gravidezes não desejadas que podem levar a uma IVG recorrente.

13.
J Psychiatr Res ; 156: 151-158, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36252344

RESUMO

There is a lack of consensus on whether routine brain magnetic resonance imaging (MRI) should be recommended as part of the initial assessment in patients with psychosis. No study so far has qualitatively assessed brain MRI in patients with early-onset psychosis (EOP), in whom neurodevelopmental factors may play a stronger role. We aimed to determine the prevalence of brain MRI findings in patients with EOP compared to healthy controls, and assess whether these findings were clinically relevant. Retrospective clinical chart review of all patients with EOP in whom a brain MRI scan was acquired during admission to an inpatient child and adolescent psychiatry unit during January 2013-December 2017, compared to age and biologically assigned gender matched healthy controls. Between group analyses tested differences in rates of qualitatively abnormal MRI scans and changes in clinical management as a result of radiological findings. A total of 256 individuals were included (128 patients with EOP and 128 healthy controls). Patients with EOP presented with a significantly higher rate of abnormal MRI scans relative to healthy controls (21.9% vs 11.7%, p = .030; OR = 2.11, [95% CI:1.06-4.17]). Radiological findings in the EOP group triggered clinical referral for further evaluation or management more often than in the healthy control group (7.0% vs 1.6%, p = .030; OR = 4.76, [95% CI:1.01-22.50]). MRI scans in youth with EOP may be characterized by an increased number of radiological abnormalities than in controls. The rates of MRI findings requiring clinical referral suggests that routine MRI acquisition may need to be considered in patients with EOP.


Assuntos
Imageamento por Ressonância Magnética , Projetos de Pesquisa , Criança , Humanos , Adolescente , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem
14.
Int J Mol Sci ; 23(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36232363

RESUMO

SARS-CoV-2 is a coronavirus family member that appeared in China in December 2019 and caused the disease called COVID-19, which was declared a pandemic in 2020 by the World Health Organization. In recent months, great efforts have been made in the field of basic and clinical research to understand the biology and infection processes of SARS-CoV-2. In particular, transcriptome analysis has contributed to generating new knowledge of the viral sequences and intracellular signaling pathways that regulate the infection and pathogenesis of SARS-CoV-2, generating new information about its biology. Furthermore, transcriptomics approaches including spatial transcriptomics, single-cell transcriptomics and direct RNA sequencing have been used for clinical applications in monitoring, detection, diagnosis, and treatment to generate new clinical predictive models for SARS-CoV-2. Consequently, RNA-based therapeutics and their relationship with SARS-CoV-2 have emerged as promising strategies to battle the SARS-CoV-2 pandemic with the assistance of novel approaches such as CRISPR-CAS, ASOs, and siRNA systems. Lastly, we discuss the importance of precision public health in the management of patients infected with SARS-CoV-2 and establish that the fusion of transcriptomics, RNA-based therapeutics, and precision public health will allow a linkage for developing health systems that facilitate the acquisition of relevant clinical strategies for rapid decision making to assist in the management and treatment of the SARS-CoV-2-infected population to combat this global public health problem.


Assuntos
COVID-19 , COVID-19/genética , COVID-19/terapia , Humanos , Pandemias , RNA Interferente Pequeno , SARS-CoV-2/genética , Transcriptoma
15.
Nefrologia (Engl Ed) ; 42(1): 85-93, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36153903

RESUMO

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spainhave adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.


Assuntos
Falência Renal Crônica , Transplante de Rim , Sobrevivência de Enxerto , Humanos , Rim , Falência Renal Crônica/cirurgia , Doadores Vivos
16.
Euro Surveill ; 27(39)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36177867

RESUMO

BackgroundThe European Centre for Disease Prevention and Control (ECDC) systematically collates information from sources to rapidly detect early public health threats. The lack of a freely available, customisable and automated early warning tool using data from Twitter prompted the ECDC to develop epitweetr, which collects, geolocates and aggregates tweets generating signals and email alerts.AimThis study aims to compare the performance of epitweetr to manually monitoring tweets for the purpose of early detecting public health threats.MethodsWe calculated the general and specific positive predictive value (PPV) of signals generated by epitweetr between 19 October and 30 November 2020. Sensitivity, specificity, timeliness and accuracy and performance of tweet geolocation and signal detection algorithms obtained from epitweetr and the manual monitoring of 1,200 tweets were compared.ResultsThe epitweetr geolocation algorithm had an accuracy of 30.1% at national, and 25.9% at subnational levels. The signal detection algorithm had 3.0% general PPV and 74.6% specific PPV. Compared to manual monitoring, epitweetr had greater sensitivity (47.9% and 78.6%, respectively), and reduced PPV (97.9% and 74.6%, respectively). Median validation time difference between 16 common events detected by epitweetr and manual monitoring was -48.6 hours (IQR: -102.8 to -23.7).ConclusionEpitweetr has shown sufficient performance as an early warning tool for public health threats using Twitter data. Since epitweetr is a free, open-source tool with configurable settings and a strong automated component, it is expected to increase in usability and usefulness to public health experts.


Assuntos
Saúde Pública , Mídias Sociais , Algoritmos , Coleta de Dados , Humanos
18.
Nat Med ; 28(4): 752-765, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35411077

RESUMO

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.


Assuntos
Neoplasias Encefálicas , Melanoma , Neoplasias Encefálicas/secundário , Irradiação Craniana , Humanos , Melanoma/radioterapia
19.
EMBO Mol Med ; 14(3): e14552, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35174975

RESUMO

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Camundongos , Recidiva Local de Neoplasia , Proteômica
20.
Front Public Health ; 10: 1027812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36761324

RESUMO

Introduction: Making epidemiological indicators for COVID-19 publicly available through websites and social media can support public health experts in the near-real-time monitoring of the situation worldwide, and in the establishment of rapid response and public health measures to reduce the consequences of the pandemic. Little is known, however, about the timeliness of such sources. Here, we assess the timeliness of official public COVID-19 sources for the WHO regions of Europe and Africa. Methods: We monitored official websites and social media accounts for updates and calculated the time difference between daily updates on COVID-19 cases. We covered a time period of 52 days and a geographic range of 62 countries, 28 from the WHO African region and 34 from the WHO European region. Results: The most prevalent categories were social media updates only (no website reporting) in the WHO African region (32.7% of the 1,092 entries), and updates in both social media and websites in the WHO European region (51.9% of the 884 entries for EU/EEA countries, and 73.3% of the 884 entries for non-EU/EEA countries), showing an overall clear tendency in using social media as an official source to report on COVID-19 indicators. We further show that the time difference for each source group and geographical region were statistically significant in all WHO regions, indicating a tendency to focus on one of the two sources instead of using both as complementary sources. Discussion: Public health communication via social media platforms has numerous benefits, but it is worthwhile to do it in combination with other, more traditional means of communication, such as websites or offline communication.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Comunicação , Europa (Continente)/epidemiologia
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