Late urinary bladder metastasis from breast cancer

reast cancer (BrC) is the most common non-dermatologic cancer in women. It frequently metastasizes to lung, liver and bone, while the urinary bladder is considered as an unusual site for BrC metastases. Materials and methods: Four years after her first oncologic surgical approach, a known BrC patient complained of a left flank pain, dysuria and urgency. Computed tomography (CT scan) imaging showed an irregular thickening of the left bladder wall and bilateral hydronephrosis. Results: A bladder metastases from BrC was diagnosed based on a histological examination of a transurethral resection of the bladder (TURB-T) specimen. Conclusions: In patients with a history of BrC, urinary bladder screening is not needful. However, if low urinary symptoms persist, an evaluation of the bladder should be considered to rule out metastatic involvement

Extraperitoneal cystectomy with ureterocutaneostomy derivation in fragile patients - should it be performed more often?

Introduction and objectives: Radical cystectomy (RC) continues to be standard of care for muscle-invasive bladder cancer and recurrent or refractory nonmuscle invasive bladder cancer. Unfortunately, it has high rates of perioperative morbidity and mortality. One of the most important predictors of postoperative outcomes is frailty, while the majority of complications are diversion related. The aim of our study was to evaluate safety of extraperitoneal cystectomy with ureterocutaneostomy in patients considered as frail. Materials and methods: We retrospectively collected data of frail patients who underwent extraperitoneal cystectomy with ureterocutaneostomy from October 2018 to August 2020 in a single center. We evaluated frailty by assessing patients' age, body mass index (BMI), nutritional status by Malnutrition Universal Screening Tool, overall health by RAI (Risk Analysis Index) and ASA (American Society of Anaesthesiologists) score, and laboratory analyses. We observed intraoperative outcomes and rates of perioperative (within 30 days) and early postoperative (within 90 days) complications (Clavien-Dindo classification). We defined extraperitoneal cystectomy with ureterocutaneostomy as safe if patients did not develop Clavien Dindo IIIb, or worse, complication. Results: A total of 34 patients, 3 female and 31 male, were analyzed. The median age was 77, BMI 26, RAI 28, ASA 3 and the majority had preexisting renal insufficiency. Blood analyses revealed presence of severe preoperative hypoalbuminemia and anemia in half of our cohort. Intraoperative median blood loss was 250 cc, whilst operative time 245 min. During perioperative period 60% of our cohort developed Clavien Dindo II complication and during early postoperative period 32% of patients required readmission. One death occurred during early postoperative period (2.9%). After 12 months of follow-up, we observed stability of the renal function for most patients. Conclusions: We believe that extraperitoneal cystectomy with ureterocutaneostomy could be considered as a treatment option for elderly and/or frail patients

Parallel evolution of amphioxus and vertebrate small-scale gene duplications

Background: Amphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Smallscale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R wholegenome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates. Results: We present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We fnd that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We fnd parallel gene duplication profles between amphioxus and vertebrates and conserved func‑tional constraints in gene duplication. Moreover, amphioxus gene duplicates show lev‑ els of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also fnd strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. foridae, with two major chromosomal rearrangements. Conclusions: In contrast to their slower molecular and morphological evolution, amphioxus' small-scale gene duplication history resembles that of the vertebrate line‑age both in quantitative and in functional terms

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium)

Purpose To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Delta 1 = POD-1 eGFR - baseline eGFR; Delta 2 = 6 months eGFR - POD-1 eGFR; Delta 3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by >= 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. Results A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ss 9.2 +/- 0.7, p < 0.001) during follow-up. Conclusion Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC

Evolution of tissue-specific transcriptomes across bilaterian animals

Regulated Gene Expression (rGE) and Alternative Splicing (rAS) are two of the main mechanisms contributing to tissue-phenotypic diversity within and between species. In this thesis, we aim at characterizing rGE and rAS patterns impacting tissue-specific transcriptomes throughout ~600 million years of bilaterian evolution. Our work revolves around (1) a vast RNA-seq dataset covering eight tissues across a symmetric phylogeny of twenty bilaterian species (eight vertebrates, eight insects and two pairs of outgroups); and (2) the exclusive focus on bilaterian-conserved genes. First, we identify ancestral tissue-specific rGE patterns, together with parallel, convergent and divergent evolutionary trajectories between and within vertebrates and insects. Second, we develop a software to infer exon orthologies at any evolutionary distance, a crucial prerequisite for rAS evolutionary analyses. Third, we characterize a compendium of tissue-specific exons across all species. Finally, we compare rGE- and rAS- regulated genes, extracting unique features associated with each type of tissue-specific regulation.La regulación de la expresión génica (rGE) y el empalme alternativo (rAS) son dos de los principales mecanismos que contribuyen a la diversidad fenotípica de tejidos dentro y entre especies. En esta tesis, nuestro objetivo es caracterizar los patrones de rGE y rAS que afectan a los transcriptomas específicos de tejido a lo largo de ~600 millones de años de evolución bilateral. Nuestro trabajo gira en torno a (1) un vasto conjunto de datos de RNA-seq que cubre ocho tejidos en una filogenia simétrica de veinte especies bilaterales (ocho vertebrados, ocho insectos y dos pares de grupos externos); y (2) el enfoque exclusivo en genes conservados bilateralmente. Primero, identificamos patrones de rGE específicos de tejidos ancestrales, junto con trayectorias evolutivas paralelas, convergentes y divergentes entre y dentro de vertebrados e insectos. En segundo lugar, desarrollamos un software para inferir ortologías de exón a cualquier distancia evolutiva, un requisito previo crucial para los análisis evolutivos de rAS. En tercer lugar, caracterizamos un compendio de exones específicos de tejido en todas las especies. Finalmente, comparamos genes regulados por rGE y rAS, extrayendo características únicas asociadas con cada tipo de regulación específica de tejido.Programa de Doctorat en Biomedicin

Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

Background: Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing. Results: We generate a massive resource for Arabidopsis thaliana, PastDB, comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets reveals that A. thaliana shows high levels of AS, similar to fruitflies, and that, compared to animals, disproportionately uses AS for stress responses. We identify core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that is tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, are overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion. Conclusions: Non-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.The research has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-StG-LS2-637591 to MI), the Spanish Ministerio de Ciencia (BFU2017-89201-P to MI), the Fundação para a Ciência e a Tecnologia (FCT) (PTDC/BIA-FBT/31018/2017 to PD and PTDC/BIA-BID/30608/2017 to GM), the “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208), EMBO Long Term postdoctoral fellowships (ALTF 1576-2016 to GM and ALTF 1505-2015 to YM), and Marie Skłodowska-Curie actions (MSCA) grants (750469 to GM and 705938 to YM). We acknowledge the support of the CERCA Programme/Generalitat de Catalunya and of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership. Funding from the R&D Unit, UIDB/04551/2020 (GREEN-IT—Bioresources for Sustainability), is also acknowledge

ExOrthist: a tool to infer exon orthologies at any evolutionary distance

Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes. However, no corresponding tool allows the detection of exon homology relationships. Here, we present ExOrthist, a fully reproducible Nextflow-based software enabling inference of exon homologs and orthogroups, visualization of evolution of exon-intron structures, and assessment of conservation of alternative splicing patterns. ExOrthist evaluates exon sequence conservation and considers the surrounding exon-intron context to derive genome-wide multi-species exon homologies at any evolutionary distance. We demonstrate its use in different evolutionary scenarios: whole genome duplication in frogs and convergence of Nova-regulated splicing networks ( https://github.com/biocorecrg/ExOrthist).The research has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-StG-LS2-637591 to MI), the Spanish Ministerio de Ciencia (BFU2017-89201-P to MI, including and FPI PhD fellowship to FM), the “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208), EMBO Long Term postdoctoral fellowship (ALTF 1505-2015 to YM), and Marie Skłodowska-Curie actions (MSCA) grant (705938 to YM). We acknowledge the support of the CERCA Programme/Generalitat de Catalunya and of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnershi

Evolution of tissue-specific expression of ancestral genes across vertebrates and insects

Data de publicació electrònica: 15-04-2024Inclou material suplementari: Supplementary Methods, Discussion, Figs. 1–12, Description of Supplementary Dataset content and References.Regulation of gene expression is arguably the main mechanism underlying the phenotypic diversity of tissues within and between species. Here we assembled an extensive transcriptomic dataset covering 8 tissues across 20 bilaterian species and performed analyses using a symmetric phylogeny that allowed the combined and parallel investigation of gene expression evolution between vertebrates and insects. We specifically focused on widely conserved ancestral genes, identifying strong cores of pan-bilaterian tissue-specific genes and even larger groups that diverged to define vertebrate and insect tissues. Systematic inferences of tissue-specificity gains and losses show that nearly half of all ancestral genes have been recruited into tissue-specific transcriptomes. This occurred during both ancient and, especially, recent bilaterian evolution, with several gains being associated with the emergence of unique phenotypes (for example, novel cell types). Such pervasive evolution of tissue specificity was linked to gene duplication coupled with expression specialization of one of the copies, revealing an unappreciated prolonged effect of whole-genome duplications on recent vertebrate evolution.This research was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-StG-LS2-637591 and ERCCoG-LS2-101002275 to M.I.), by the Spanish Ministry of Economy and Competitiveness (BFU-2017-89201-P and PID2020-115040GB-I00 to M.I.) and by the ‘Centro de Excelencia Severo Ochoa 2013-2017’(SEV-2012-0208). F.M. holds a FPI fellowship associated with the grant BFU-2017-89201-P. Additional support for this research was provided by the Spanish MINECO (PGC2018-098427- B-I00 to D.M. and X.F.-M.), the Czech Science Foundation (22-21244S to M.N.), the Australian Research Council (grant DP200103219 to P.D.C. and F.T.) and the National Institutes of Health-NIAID (grant R21AI167849 to F.G.N.)