Short-term prognosis of polypharmacy in elderly patients treated in emergency departments: results from the EDEN project.

Background: Polypharmacy is a growing phenomenon among elderly individuals. However, there is little information about the frequency of polypharmacy among the elderly population treated in emergency departments (EDs) and its prognostic effect. This study aims to determine the prevalence and short-term prognostic effect of polypharmacy in elderly patients treated in EDs. Methods: A retrospective analysis of the Emergency Department Elderly in Needs (EDEN) project's cohort was performed. This registry included all elderly patients who attended 52 Spanish EDs for any condition. Mild and severe polypharmacy was defined as the use of 5-9 drugs and ⩾10 drugs, respectively. The assessed outcomes were ED revisits, hospital readmissions, and mortality 30 days after discharge. Crude and adjusted logistic regression analyses, including the patient's comorbidities, were performed. Results: A total of 25,557 patients were evaluated [mean age: 78 (IQR: 71-84) years]; 10,534 (41.2%) and 5678 (22.2%) patients presented with mild and severe polypharmacy, respectively. In the adjusted analysis, mild polypharmacy and severe polypharmacy were associated with an increase in ED revisits [odds ratio (OR) 1.13 (95% confidence interval (CI): 1.04-1.23) and 1.38 (95% CI: 1.24-1.51)] and hospital readmissions [OR 1.18 (95% CI: 1.04-1.35) and 1.36 (95% CI: 1.16-1.60)], respectively, compared to non-polypharmacy. Mild and severe polypharmacy were not associated with increased 30-day mortality [OR 1.05 (95% CI: 0.89-2.26) and OR 0.89 (95% CI: 0.72-1.12)], respectively. Conclusion: Polypharmacy was common among the elderly treated in EDs and associated with increased risks of ED revisits and hospital readmissions ⩽30 days but not with an increased risk of 30-day mortality. Patients with polypharmacy had a higher risk of ED revisits and hospital readmissions ⩽30 days after discharge.

Short-term prognosis of polypharmacy in elderly patients treated in emergency departments: results from the EDEN project Management elderly patients with polypharmacy is becoming a major challenge to the emergency services. The progressive aging of the population is producing a progressive increase in the number of patients treated with multiple comorbidities and chronic medications. It's well known that polypharmacy is associated with an increase in hospital admissions and health care system costs. However, the impact of polypharmacy over the risk of new visits to the emergency rooms is not well defined. Understanding the impact of polypharmacy on the frequency of new visits to the emergency room and on patient mortality is the first step to establish prevention measures for new visits, proposing improvements in chronic treatment at discharge. This study aimed to determine the prevalence and effect on short-term prognosis of polypharmacy in elderly patients treated in Emergency departments. The authors used a retrospective multipurpose registry in 52 hospitals in Spain. This study includes 25,557 patients with a mean age of 78 years. On admission, the median number of drugs was 6 (IQR: 3­9), with 10,534 (41.2%) patients taking 5­9 drugs and 5,678 (22.2%) taking ⩾10 drugs. In these patients comorbidities were associated with an increase in the number of drugs. In the patients with severe polypharmacy (⩾10 drugs), diuretics were the most frequently drugs prescribed, followed by antihypertensives and statins. The results obtained indicate that polypharmacy is a frequent phenomenon among the elderly population treated in Emergency departments, being antihypertensives the most frequently used drugs in this population. Those patients who takes ⩾10 drugs have a higher risk of new visits to the emergency room and hospital readmissions in short term period.

Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer.

DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 cancer genomes followed by the interrogation of CRISPR-Cas9 loss-of-function screens across >700 cancer cell lines, we determined that passenger coamplifications are accompanied by distinct dependency profiles. In a proof-of-principle study, we demonstrate that the coamplification of the bona fide passenger gene DEAD-Box Helicase 1 (DDX1) creates an increased dependency on the mTOR pathway. Interaction proteomics identified tricarboxylic acid (TCA) cycle components as previously unrecognized DDX1 interaction partners. Live-cell metabolomics highlighted that this interaction could impair TCA activity, which in turn resulted in enhanced mTORC1 activity. Consequently, genetic and pharmacologic disruption of mTORC1 resulted in pronounced cell death in vitro and in vivo. Thus, structurally linked coamplification of a passenger gene and an oncogene can result in collateral vulnerabilities. SIGNIFICANCE: We demonstrate that coamplification of passenger genes, which were largely neglected in cancer biology in the past, can create distinct cancer dependencies. Because passenger coamplifications are frequent in cancer, this principle has the potential to expand target discovery in oncology. This article is featured in Selected Articles from This Issue, p. 384.

Elimusertib has Antitumor Activity in Preclinical Patient-Derived Pediatric Solid Tumor Models.

The small-molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities in adults and children. Its preclinical antitumor activity in pediatric malignancies, however, is largely unknown. We here assessed the preclinical activity of elimusertib in 38 cell lines and 32 patient-derived xenograft (PDX) models derived from common pediatric solid tumor entities. Detailed in vitro and in vivo molecular characterization of the treated models enabled the evaluation of response biomarkers. Pronounced objective response rates were observed for elimusertib monotherapy in PDX, when treated with a regimen currently used in clinical trials. Strikingly, elimusertib showed stronger antitumor effects than some standard-of-care chemotherapies, particularly in alveolar rhabdomysarcoma PDX. Thus, elimusertib has strong preclinical antitumor activity in pediatric solid tumor models, which may translate to clinically meaningful responses in patients.

Learning from history in the midst of the COVID-19: epidemics/pandemics of antiquity up to the fall of the Western Roman Empire / Aprendiendo de la historia en medio del COVID-19: epidemias/pandemias de la antigüedad hasta la caída del Imperio Romano de Occidente

Abstract When humans discovered agriculture and livestock, they ceased to be nomads and began to settle in towns until they created large cities. From the first human settlements in Egypt, Mesopotamia, and the Anatolian Peninsula, populations were exposed and susceptible to new infectious agents, leading to epidemics and pandemics. Great civilizations emerged, such as Egypt, the land of Hatti, Israel, Greece, Carthage, and Rome, among others. Contact between different populations through wars or maritime trade is well documented and has been described as a source of epidemics throughout history. Epidemics described as plagues or pestilences, such as those of Egypt, the Hebrews, or the Hittites, are based on biblical texts or evidence such as tablets or hieroglyphic writings. We also reviewed classical books by authors such as Homer, Aeschylus, Herodotus of Halicarnassus, Thucydides, Diodorus Siculus, Dionysius of Halicarnassus, Titus Livius, Suetonius, and others; and described all epidemics/pandemics chronologically. This article describes the epidemics/pandemics for which there is written evidence from ancient Egypt to the fall of the Roman Empire. We should not be surprised when new epidemics/pandemics appear as causes of political and economic collapse, as this has been common throughout history, decimating, blocking, or even destroying cultures and civilizations repeatedly.

Resumen Cuando el hombre descubrió la agricultura y la ganadería, dejó de ser nómada y empezó a asentarse en pueblos hasta crear grandes ciudades. Desde los primeros asentamientos humanos en Egipto, Mesopotamia y la península de Anatolia, las poblaciones estuvieron expuestas y susceptibles a nuevos agentes infecciosos, dando lugar a epidemias y pandemias. Aparecieron grandes civilizaciones como Egipto, la Tierra de Hatti, Israel, Grecia, Cartago y Roma, entre otras. El contacto entre las distintas poblaciones a través de las guerras o el comercio marítimo está muy bien establecido y descrito como focos de epidemias a lo largo de la historia. Las epidemias descritas como plagas o pestilencias, como las que ocurrieron a los egipcios, los judíos, o los hititas, se describen con base en textos bíblicos o mediante evidencias como tablillas o escritos jeroglíficos. También revisamos libros clásicos de autores como Homero, Esquilo, Herodoto de Halicarnaso, Tucídides, Diodoro Sículo, Dionisio de Halicarnaso, Tito Livio, Suetonio, entre otros. Este artículo describe cronológicamente todas las epidemias/pandemias de las que existe evidencia a través de la escritura desde el antiguo Egipto hasta la caída del Imperio Romano. No debemos sorprendernos cuando aparecen nuevas epidemias/pandemias como causantes del colapso político y económico, ya que ha sido algo común a lo largo de la historia, diezmando, bloqueando o incluso destruyendo culturas y civilizaciones reiteradamente.

Preoperative CA19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: A further plea for biological resectability criteria.

INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.

Coordinated inheritance of extrachromosomal DNA species in human cancer cells.

The chromosomal theory of inheritance has dominated human genetics, including cancer genetics. Genes on the same chromosome segregate together while genes on different chromosomes assort independently, providing a fundamental tenet of Mendelian inheritance. Extrachromosomal DNA (ecDNA) is a frequent event in cancer that drives oncogene amplification, dysregulated gene expression and intratumoral heterogeneity, including through random segregation during cell division. Distinct ecDNA sequences, herein termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells. However, how multiple ecDNA species within a tumor cell are assorted and maintained across somatic cell generations to drive cancer cell evolution is not known. Here we show that cooperative ecDNA species can be coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. EcDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy number gains in multiple ecDNA species prior to any selection. Computational modeling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Finally, we show that coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations.

Juventud y educación digital en tiempos de pandemia: el caso de una universidad mexicana

Los grupos que se han visto más impactado por la pandemia por COVID-19, en las instituciones de Educación Superior, fueron los estudiantes. Por tal motivo, se realizó un estudio con enfoque cualitativo en la Universidad Veracruzana, México, con la finalidad de conocer sus experiencias personales, tecnológicas y escolares durante la pandemia, así como sus expectativas post/pandemia. Los resultados invitan a reflexionar sobre diversas estrategias para el diseño de políticas educativas orientadas a apoyar la formación de los estudiantes universitarios. El presente trabajo de investigación se reconoce que las condiciones estructurales de la desigualdad social y brecha digital de los universitarios no son las más óptimas para su formación universitaria en modalidad presencial, virtual o hibrida, en este sentido, es posible detectar ciertas dificultades estructurantes en el ámbito escolar de los jóvenes universitarios y la falta de crear y constituir una universidad hibrida en las instituciones de educación superior.

The groups that have been most impacted by the COVID-19 pandemic, in Higher Education institutions, were the students. For this reason, a qualitative study was conducted at the Universidad Veracruzana, Mexico, in order to learn about their personal, technological, and school experiences during the pandemic, as well as their post-pandemic expectations. The results invite to reflect on different strategies for the design of educational policies geared to support the education of university students.

The slowdown of new infections by human retroviruses has reached a plateau in Spain.

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.

Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells.

Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond.

Chemical and sensory assessment of extra virgin olive oil blends with omega-3 polyunsaturated fatty acids from plant origin

Extra virgin olive oil (EVOO) is known for its health benefits, although it provides a minimum amount of n-3 polyunsaturated fatty acids (n-3 PUFA), which play an important role in the human organism. In this study, EVOO was blended with vegetable oils which are rich sources of n-3 PUFA alpha-linolenic acid (ALA) and/or stearidonic acid (SDA) (chia, walnut, linseed and viper's bugloss seed oils). Fatty acid profiles, induction time, and organoleptic characteristics of the resulting blends were assessed. The n-3 PUFA enrichment in the blends was proportional to the degree of blending. Sensory analysis carried out by a trained panel showed that it is possible to enrich EVOO with up to 20% chia, linseed and viper's bugloss seed oil without altering the original organoleptic characteristics of EVOO. However, the induction time of the blends was significantly reduced compared with EVOO even after adding n-3 PUFA in small proportions, meaning that shelf-life time of these blends is much lower than that of EVOO, which should be considered when preparing these products for commercial purposes.

El aceite de oliva extra virgen (AOEV) es ampliamente conocido por sus beneficios para la salud, aunque apenas aporta ácidos grasos poliinsaturados n-3 (AGPI n-3), los cuales juegan un papel importante en el organismo humano. En este estudio se elaboraron mezclas de AOEV con aceites vegetales ricos en ácido alfa-linolénico (ALA) y/o estearidónico (SDA) (chia, nuez, linaza y viborera). Se evaluaron los perfiles de ácidos grasos, tiempos de inducción y características organolépticas de las mezclas resultantes. El enriquecimiento en AGPI n-3 fue proporcional al grado de mezcla. El análisis sensorial llevado a cabo por un panel entrenado mostró que es posible enriquecer AOEV con hasta un 20% de aceite de chia, linaza o viborera sin alterar las características organolépticas originales del AOEV. Sin embargo, los tiempos de inducción de las mezclas fueron significativamente menores que el del AOEV, incluso tras añadir AGPI n-3 en pequeñas proporciones, lo que significa que el tiempo de vida media de las mezclas es mucho menor que el del AOEV. Este hecho debería tenerse en cuenta al preparar las mezclas con propósitos comerciales.

Table olive elicits antihypertensive activity in spontaneously hypertensive rats.

BACKGROUND: Table olives are a food with a high content of bioactive compounds with cardioprotective properties, such as oleic acid, polyphenols, and pentacyclic triterpenes. Here, we investigate the effect of the intake of table olives on blood pressure (BP) and body weight in spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats. 'Arbequina' table olives (3.85 g kg-1 ) were administered by gavage to SHR and WKY rats in short-term (1 day) and long-term (7 weeks) experiments. BP was measured by the tail-cuff method, and polyphenols and triterpenes were determined in olives and plasma by liquid chromatography-mass spectrometry. RESULTS: Administration of 'Arbequina' olives to WKY rats did not exert any change in BP in any of the experiments. However, in SHR, the single dose induced a transient reduction in BP of approximately 15 mmHg, from the second to the tenth hour after the administration. In the long-term assay, a similar decrease was established in the second week and was maintained throughout the experiment. Moreover, the daily administration of olives to rats did not affect their body weight when compared with controls in either the WKY rats or SHR. The determination of polyphenols and triterpenes in plasma indicated that, at the end of the experiment, only maslinic acid, oleanolic acid, hydroxytyrosol, and luteolin were found, all of them being compounds with already described capacity to decrease BP. CONCLUSION: The results suggest that the daily intake of table olives could decrease BP in hypertension without affecting body weight, indicating that table olives could contribute to improving cardiovascular health. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH.

Extrachromosomal DNA (ecDNA) is a common mode of oncogene amplification but is challenging to analyze. Here, we adapt CRISPR-CATCH, in vitro CRISPR-Cas9 treatment and pulsed field gel electrophoresis of agarose-entrapped genomic DNA, previously developed for bacterial chromosome segments, to isolate megabase-sized human ecDNAs. We demonstrate strong enrichment of ecDNA molecules containing EGFR, FGFR2 and MYC from human cancer cells and NRAS ecDNA from human metastatic melanoma with acquired therapeutic resistance. Targeted enrichment of ecDNA versus chromosomal DNA enabled phasing of genetic variants, identified the presence of an EGFRvIII mutation exclusively on ecDNAs and supported an excision model of ecDNA genesis in a glioblastoma model. CRISPR-CATCH followed by nanopore sequencing enabled single-molecule ecDNA methylation profiling and revealed hypomethylation of the EGFR promoter on ecDNAs. We distinguished heterogeneous ecDNA species within the same sample by size and sequence with base-pair resolution and discovered functionally specialized ecDNAs that amplify select enhancers or oncogene-coding sequences.

Enrichment of Astrocyte-Derived Extracellular Vesicles from Human Plasma.

Extracellular vesicles (EVs) are biological nanoparticles secreted by all cells for cellular communication and waste elimination. They participate in a vast range of functions by acting on and transferring their cargos to other cells in physiological and pathological conditions. Given their presence in biofluids, EVs represent an excellent resource for studying disease processes and can be considered a liquid biopsy for biomarker discovery. An attractive aspect of EV analysis is that they can be selected based on markers of their cell of origin, thus reflecting the environment of a specific tissue in their cargo. However, one of the major handicaps related to EV isolation methods is the lack of methodological consensuses and standardized protocols. Astrocytes are glial cells with essential roles in the brain. In neurodegenerative diseases, astrocyte reactivity may lead to altered EV cargo and aberrant cellular communication, facilitating/enhancing disease progression. Thus, analysis of astrocyte EVs may lead to the discovery of biomarkers and potential disease targets. This protocol describes a 2-step method of enrichment of astrocyte-derived EVs (ADEVs) from human plasma. First, EVs are enriched from defibrinated plasma via polymer-based precipitation. This is followed by enrichment of ADEVs through ACSA-1-based immunocapture with magnetic micro-beads, where resuspended EVs are loaded onto a column placed in a magnetic field. Magnetically labeled ACSA-1+ EVs are retained within the column, while other EVs flow through. Once the column is removed from the magnet, ADEVs are eluted and are ready for storage and analysis. To validate the enrichment of astrocyte markers, glial fibrillary acidic protein (GFAP), or other specific astrocytic markers of intracellular origin, can be measured in the eluate and compared with the flow-through. This protocol proposes an easy, time-efficient method to enrich ADEVs from plasma that can be used as a platform to examine astrocyte-relevant markers.

Extrachromosomal DNA amplifications in cancer.

Extrachromosomal DNA (ecDNA) amplification is an important driver alteration in cancer. It has been observed in most cancer types and is associated with worse patient outcome. The functional impact of ecDNA has been linked to its unique properties, such as its circular structure that is associated with altered chromatinization and epigenetic regulatory landscape, as well as its ability to randomly segregate during cell division, which fuels intercellular copy number heterogeneity. Recent investigations suggest that ecDNA is structurally more complex than previously anticipated and that it localizes to specialized nuclear bodies (hubs) and can act in trans as an enhancer for genes on other ecDNAs or chromosomes. In this Review, we synthesize what is currently known about how ecDNA is generated and how its genetic and epigenetic architecture affects proto-oncogene deregulation in cancer. We discuss how recently identified ecDNA functions may impact oncogenesis but also serve as new therapeutic vulnerabilities in cancer.

Therapeutic targeting of ATR in alveolar rhabdomyosarcoma.

Despite advances in multi-modal treatment approaches, clinical outcomes of patients suffering from PAX3-FOXO1 fusion oncogene-expressing alveolar rhabdomyosarcoma (ARMS) remain dismal. Here we show that PAX3-FOXO1-expressing ARMS cells are sensitive to pharmacological ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Expression of PAX3-FOXO1 in muscle progenitor cells is not only sufficient to increase sensitivity to ATR inhibition, but PAX3-FOXO1-expressing rhabdomyosarcoma cells also exhibit increased sensitivity to structurally diverse inhibitors of ATR. Mechanistically, ATR inhibition leads to replication stress exacerbation, decreased BRCA1 phosphorylation and reduced homologous recombination-mediated DNA repair pathway activity. Consequently, ATR inhibitor treatment increases sensitivity of ARMS cells to PARP1 inhibition in vitro, and combined treatment with ATR and PARP1 inhibitors induces complete regression of primary patient-derived ARMS xenografts in vivo. Lastly, a genome-wide CRISPR activation screen (CRISPRa) in combination with transcriptional analyses of ATR inhibitor resistant ARMS cells identifies the RAS-MAPK pathway and its targets, the FOS gene family, as inducers of resistance to ATR inhibition. Our findings provide a rationale for upcoming biomarker-driven clinical trials of ATR inhibitors in patients suffering from ARMS.

Development of a prediction model of pancreatic fistula after duodenopancreatectomy and soft pancreas by assessing the preoperative image.

BACKGROUND: Pancreatic consistency is one of the most widely accepted risk factors of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatectoduodenectomy (PD). The present study aims to identify preoperative characteristics from the preoperative computed tomography (CT) associated with an increased risk. METHODS: Retrospective observational cohort study of patients who underwent PD surgery (January 2010-2019) were enrolled. All patients with available preoperative imaging were included; 103 met the inclusion criteria. Several parameters were measured on preoperative abdominal CT: retrorenal adipose tissue; abdominal perimeter; total adipose tissue, visceral and subcutaneous; skeletal muscle mass; main pancreatic duct (MPD) diameter; pancreatic thickness; remnant pancreatic volume; pancreatic attenuation (pancreas-to-spleen ratio). Primary endpoints were the association of radiological variables with soft pancreatic consistency and POPF development. All variables possibly associated with POPF and soft pancreas were subsequently included into a multivariable logistic regression model. RESULTS: Soft pancreas consistency was found in 43 patients (41.7%) and CR-POPF was higher (51.2% vs. 18%, p < 0.001). Multivariable analysis identified MPD ≤ 3 mm (OR = 7.2, 95%CI 2.3-23, p = 0.001), a remnant pancreatic volume ≥ 20 cm3 (OR = 6.4, 95%CI 2-21, p = 0.041), pancreas-to-spleen < 0.8 (OR = 3.2, 95%CI 1.2-8.4, p = 0.039), and retrorenal adipose tissue ≥ 12 cm3 (OR = 5.3, 95%CI 1.8-15.7, p = 0.013). Multivariable analysis showed MPD ≤ 3 mm (OR = 8.25, 95%CI 2.2-30.8, p = 0.002) and total adipose tissue ≥ 190 cm3 (OR = 3.2, 95%CI 1.1-9.1, p = 0.0027) were independent predictors of CR-POPF. CONCLUSION: The preoperative assessment of MPD, remnant pancreatic volume, pancreas-to-spleen ratio, total adipose tissue, and retrorenal adipose tissue are associated with soft pancreas texture and the risk of CR-POPF.

Detection and Validation of Circular DNA Fragments Using Nanopore Sequencing.

Occurrence of extra-chromosomal circular DNA is a phenomenon frequently observed in tumor cells, and the presence of such DNA has been recognized as a marker of adverse outcome across cancer types. We here describe a computational workflow for identification of DNA circles from long-read sequencing data. The workflow is implemented based on the Snakemake workflow management system. Its key step uses a graph-theoretic approach to identify putative circular fragments validated on simulated reads. We then demonstrate robustness of our approach using nanopore sequencing of selectively enriched circular DNA by highly sensitive and specific recovery of plasmids and the mitochondrial genome, which is the only circular DNA in normal human cells. Finally, we show that the workflow facilitates detection of larger circular DNA fragments containing extrachromosomal copies of the MYCN oncogene and the respective breakpoints, which is a potentially useful application in disease monitoring of several cancer types.

Terapia nasal de alto flujo en insuficiencia respiratoria grave por SARS-CoV-2 / High-flow nasal therapy in severe respiratory failure due to SARS-CoV-2

Resumen El uso de terapia nasal de alto flujo (TNAFO) en pacientes con insuficiencia respiratoria aguda grave (IRAG) por neumonía COVID-19 (NCOVID-19) es debatido. Ante la falta de camas en Unidades de Cuidados Intensivos en el Sistema de Salud Pública de la Provincia del Neuquén, se implementó su uso en salas generales. Con el objetivo de describir la experiencia de uso de la TNAFO en pacientes con IRAG por NCOVID-19, se llevó a cabo este estudio retrospectivo multicéntrico. El resultado primario fue la frecuencia de destete exitoso de TNAFO y la mortalidad intrahospitalaria (MIH). Se analizaron 299 pacientes, de éstos, 120 (40.1%) fueron retirados con éxito de la TNAFO. Esta fracasó en 59.8% (179), 44.1% (132) requirió ventilación mecánica invasiva (VMI) y 15.7% (47) no eran candidatos a la intubación. Un índice ROX ≥ 5 a las 6 h después del inicio, se asoció con el éxito de la TNAFO (OR 0.26 [IC 95% 0.15-0.46] p<0.0001). La MIH general fue del 48.5% (145/299), 70.4% (93/132) en aquellos con VMI, 4.2% (5/120) falleció post destete exitoso de la TNAFO y 100% (47/47) en el grupo no candidatos a la intubación. Los pacientes con TNAFO tuvieron una disminución estadísticamente significativa en la MIH y en días de internación. El uso de TNAFO en salas generales logró una reducción en la utilización de VMI, con una reducción de la mortalidad y días de estada en los internados por NCOVID-19 con IRAG.

Abstract The use of high-flow nasal therapy (HFNT) in patients with severe acute respiratory failure (SARF) due to COVID-19 pneu monia (NCOVID-19) is debated. Given the lack of beds in Intensive Care Units in the Public Health System of the Province of Neuquén, their use was implemented in general wards. This restrospective multicenter study was carried out to describe the experience of using HNFT in patients with SARF due to NCOVID-19. The primary outcome was the frequency of successful weaning from HFNT and in-hospital mortality (IHM). Two hundred ninety-nine patients were analyzed; 120 (40.1%) were successfully withdrawn from HFNT. This failed in 59.8% (179), 44.1% (132) required invasive mechanical ventilation (IMV), and 15.7% (47) was not candidates for intubation. A ROX index ≥ 5 at 6 h after initiation was associated with the success of HFNT (OR 0.26 [IC 95% 0.15-0.46] p<0.0001). The general IHM was 48.5% (145/299), 70.4% (93/132) in patients with IMV, 4.2% (5/120) died after successful weaning from HFNT and 100% (47/47) in the group not candidates for intubation. Patients with TNAFO had a statistically significant decrease in MIH and days of hospitalization. TNAFO in general wards achieved a decrease in the use of IMV, with a reduction in mortality and days of stay in hospitalized for NCOVID-19 with SARF.

Patients' Perceived Satisfaction Through Telephone-Assisted Tele-Consultation During the SARS-CoV-2 Pandemic Period: Observational Single-Centre Study at a Tertiary-Referral Colorectal Surgery Department.

Introduction: The pandemic produced by SARS-CoV-2 has obliged us to set up the tele-assistance to offer a continuity of care. This implies an innovation, being the degree of satisfaction of patients unknown. Methods: A telephonic survey was conducted with the validated in the Spanish tool Telehealth Usability Questionnaire (Telehealth Usability Questionnaire; rating from 1-7) of all candidate patients assisted consecutively in the Coloproctology Unit. We included demographic variables, education level, job status, diagnosis and consultation type. A descriptive study was done. The relationship between the willingness of consultation model in the future (telemedicine vs traditional) and the categorical variables was analysed through the chi-squared test. Results: A total of 115 patients were included. The average age was 59.9 years, being 60% women. The average score in each of the survey items was higher than 6 in all the questions but 1. 26.1% of the surveyed patients confessed being advocated to tele-assistance in the future. The only factors related to greater willingness to tele-assistance were male gender (37% vs 18.8%; P = .03) and a higher academic preparation level in favour of higher technical studies (35.9%) and university studies (32.4%) opposite to the rest (P = .043). The rest of variables studied, job status, labour regimen, diagnostic group and consultation type did not show any relationship. Conclusions: A vast majority of patients answered favourably to almost all the items of the survey. However, only 26.1% of them would choose a model of tele-assistance without restrictions.