RAD51 restricts DNA over-replication from re-activated origins.

Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation.

UAP56/DDX39B is a major cotranscriptional RNA-DNA helicase that unwinds harmful R loops genome-wide.

Nonscheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R-loop accumulation. One mechanism relies on the conserved THO complex in association with cotranscriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R-loop removal. We show that UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork stalling. We demonstrate an RNA-DNA helicase activity in UAP56 and show that its overexpression suppresses R loops and genome instability induced by depleting five different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA-DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful cotranscriptional RNA structures that otherwise would block transcription and replication.

Influence of different midsole foam in advanced footwear technology use on running economy and biomechanics in trained runners.

BACKGROUND: Ethylene and vinyl acetate (EVA) and polyether block amide (PEBA) are recently the most widely used materials for advanced footwear technology (AFT) that has been shown to improve running economy (RE). This study investigated the effects of these midsole materials on RE and biomechanics, in both fresh and worn state (after 450 km). METHODS: Twenty-two male trained runners participated in this study. Subjects ran four 4-min trials at 13 km‧h-1 with both fresh EVA and PEBA AFT and with the same models with 450 km of wear using a randomized crossover experimental design. We measured energy cost of running (W/kg), spatiotemporal, and neuromuscular parameters. RESULTS: There were significant differences in RE between conditions (p = 0.01; n2 = 0.17). There was a significant increase in energy cost in the worn PEBA condition compared with new (15.21 ± 1.01 and 14.87 ± 0.99 W/kg; p < 0.05; ES = 0.54), without differences between worn EVA (15.13 ± 1.14 W/kg; p > 0.05), and new EVA (15.15 ± 1.13 w/kg; ES = 0.02). The increase in energy cost between new and worn was significantly higher for the PEBA shoes (0.32 ± 0.38 W/kg) but without significant increase for the EVA shoes (0.06 ± 0.58 W/kg) (p < 0.01; ES = 0.51) with changes in step frequency and step length. The new PEBA shoes had lower energy cost than the new EVA shoes (p < 0.05; ES = 0.27) with significant differences between conditions in contact time. CONCLUSION: There is a clear RE advantage of incorporating PEBA versus EVA in an AFT when the models are new. However, after 450 km of use, the PEBA and EVA shoes had similar RE.

Intergenerational sex and early sexual debut are associated with HIV infection among transgender women in Paraguay.

INTRODUCTION: HIV prevalence among transgender women is high worldwide. The objectives of the present study were to estimate the current prevalence of HIV and identify factors associated with high HIV burden among transgender women in Paraguay. METHODS: Transgender women aged ≥15 years in four regions of Paraguay were recruited by Starfish sampling between February and March 2021. RESULTS: In total, 322 transgender women were included. Mean age was 31 years (range 15-67), and 102 had positive HIV test results (31.7%, 95% confidence interval [CI] 26.6-37.1). In multivariable analysis, factors associated with HIV infection were age at first intercourse ≤17 years (adjusted odds ratio [aOR] 5.47; 95% CI 1.05-28.42), >10 years difference in age with the last sexual partner (aOR 1.60; 95% CI 1.04-2.46), substance use (mostly cocaine) (aOR 3.00; 95% CI 1.47-6.12), higher risk perception (aOR 3.08; 95% CI 1.53-6.17), not testing for HIV (aOR 1.23; 95% CI 1.09-1.39), and accessed by a peer educator (aOR 3.86; 95% CI 1.77-8.38). CONCLUSIONS: Sexual debut as a minor and a large age difference with sexual partners are associated with high burden of HIV among transgender women in Paraguay. Our study corroborates the finding of cocaine use during sex as a risk factor for HIV. Prevention programmes must address structural and social vulnerabilities to stem the tragically high burden of HIV among transgender women.

Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy.

Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.

Trends in mortality from cardiovascular diseases in Chile, 2000-2020.

Objective: To analyze trends in mortality caused by cardiovascular diseases (CVD) in Chile during the period 2000-2020. Methods: Data on age-adjusted mortality rates (AAMR) from CVD per 100 000 population in Chile for 2000-2020 were extracted from the World Health Organization Mortality Database. Joinpoint regression was used to analyze the trends and compute the average annual percent change (AAPC) in Chile. In addition, analyses were conducted by sex and type of CVD. Results: Between 2000 and 2020, the AAMR from CVD decreased in Chile from 159.5 to 94.6 per 100 000 population, with a statistically significant decrease in the AAPC of 2.6% (95% CI [-2.8, -2.4]). No joinpoints were identified. The AAMR from CVD decreased annually by 2.6% (95% CI [-2.8, -2.4]) and 2.8% (95% CI [-3.5, -2.6]) in men and women, respectively. The AAMR from ischemic heart disease reduced annually by 3.6% (95% CI [-4.6, -2.7]) with two joinpoints in 2011 and 2015. In the case of stroke, the mortality rate decreased annually by 3.7% (95% CI [-4.5, -3.0]), with two joinpoints in 2008 and 2011. Conclusions: Cardiovascular disease mortality rates have decreased significantly in Chile, in both sexes, especially in women. This decrease could be explained mainly by a significant reduction in the case fatality in recent decades. These results could be a reference for developing primary prevention and acute management of CVD policies focused on populations with higher mortality.

Oxidative damage associated with exposure to heavy metals present in topsoils in central Chile.

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.

Structural validity and reliability of the "Oral Health Assessment Tool" applied by speech-language therapists in a population of older Chilean people.

BACKGROUND: A good state of oral health allows people to communicate and eat. This topic is relevant in older people given its close relationship with their general health. At present, health challenges are directed at detecting and preventing oral disorders and are seen to exclusively by dentists, because the existing instruments can only be applied by them. However, speech-language therapists undergo similar training, which would allow them to collaborate in these processes. In this context, the Oral Health Assessment Tool (OHAT) is a detection instrument with good psychometric properties that is currently available for non-dental use. The objective of this study is the translation into Chilean Spanish of the OHAT and a structural validation of that version for application by these professionals. MATERIALS AND METHODS: A mixed qualitative-quantitative study was carried out. The OHAT instrument was adapted to Chilean Spanish and subsequently subject to structural validity and evaluation of internal consistency reliability, as well as a valuation of its reproducibility in 286 older people (166 female, 120 male) from different health contexts. RESULTS: The cultural adaptation of the instrument proved to be semantically consistent with the original instrument. Its application was considered to be speedy and simple in the pre-test. The confirmatory factor analysis evidenced the unidimensionality of the OHAT. In addition, the instrument shows good internal consistency and test-retest reliability. CONCLUSIONS: The OHAT instrument was considered to possess adequate structural validity and test-retest reliability properties. Its usefulness in the context of oral health disorders of this population in Chile is discussed.

Spanish version of the Pediatric Anesthesia Emergence Delirium scale: translation and cross-cultural adaptation.

BACKGROUND: Emergence delirium (ED) is a mental disturbance in children during recovery from general anaesthesia. The Pediatric Anesthesia Emergence Delirium (PAED) scale is the only validated scale that assesses ED in paediatric patients undergoing general anaesthesia. The aim of this study was the translation and cross-cultural adaptation of the PAED scale into Spanish (Chile).  METHODS: A five-stage translation and cross-cultural adaptation process was carried out. The reliability of the Spanish version of the PAED scale was evaluated in paediatric patients independently by a set of two raters (anaesthesiologists or postanaesthesia care unit nurses) in the postanaesthetic period after major outpatient surgery. ED was defined by a cut-off level of ≥ 10 points on the PAED scale.  RESULTS: The PAED scale was evaluated in 353 consecutive children. Patients had a mean age of 7.4 ± 3.22 years. The preoperative ASA Physical Status class was 62%, 37%, and 1% (ASA class I, II and III, respectively). The distribution of patients by service was as follows: 45% of patients underwent paediatric surgery; 33% underwent otorhinolaryngological surgery; 11% underwent orthopaedic surgery; 10% underwent ophthalmological surgery; and 1% underwent other types of surgery. The interrater agreement ranged from 96.9% to 97.9%, with Kappa values ranging from 0.59 to 0.79. The Cronbach's alpha value was 0.91. The ED global incidence was 9.1% and was higher in the younger age groups (3-10 years). CONCLUSIONS: The translated and cross-culturally adapted Spanish version of the PAED scale is a reliable instrument to measure ED in the postanaesthetic period in Chilean children.

Optimization of the Polarization Profile of Conical-Shaped Shells Piezoelectric Sensors.

Conical shell structures are frequently submitted to severe static and dynamic mechanical loads that can result in situations that affect the service of the systems that are part of, or even cause catastrophic failures. For this reason, a common solution is to design an active deformation control system, usually using piezoelectric patches strategically distributed along the surface of the shell structure. Moreover, these elements may be part of an energy recovery system. This paper details the methodology to topologically optimize the placement of piezoelectric elements through a characteristic function, analysing static and free vibration loading cases by means of the finite element method. Then, the optimal arrangement of the electrode with different polarization profiles is distributed throughout the entire structure. The nature of the loading cases studied corresponds to a general situation where static loads and dynamics vibration are considered. The objective function of the problem only depends linearly on the displacement fields, and therefore, the optimal electrode profile can be obtained for any combination of loads. As a consequence, this technique allows for maximising the electric charge obtained, which results in a greater capacity for monitoring, actuation and/or energy harvesting.

Cleavage of LOXL1 by BMP1 and ADAMTS14 Proteases Suggests a Role for Proteolytic Processing in the Regulation of LOXL1 Function.

Members of the lysyl oxidase (LOX) family catalyze the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin in the initiation step of the formation of covalent cross-links, an essential process for connective tissue maturation. Proteolysis has emerged as an important level of regulation of LOX enzymes with the cleavage of the LOX isoform by metalloproteinases of the BMP1 (bone morphogenetic protein 1) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) families as a model example. Lysyl oxidase-like 1 (LOXL1), an isoform associated with pelvic organ prolapse and pseudoexfoliation (PEX) glaucoma, has also been reported to be proteolytically processed by these proteases. However, precise molecular information on these proteolytic events is not available. In this study, using genetic cellular models, along with proteomic analyses, we describe that LOXL1 is processed by BMP1 and ADAMTS14 and identify the processing sites in the LOXL1 protein sequence. Our data show that BMP1 cleaves LOXL1 in a unique location within the pro-peptide region, whereas ADAMTS14 processes LOXL1 in at least three different sites located within the pro-peptide and in the first residues of the catalytic domain. Taken together, these results suggest a complex regulation of LOXL1 function by BMP1- and ADAMTS14-mediated proteolysis where LOXL1 enzymes retaining variable fragments of N-terminal region may display different capabilities.

BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice.

BACKGROUND/OBJECTIVES: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. METHODS: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. RESULTS: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. CONCLUSIONS: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity.

The DNA damage response acts as a safeguard against harmful DNA-RNA hybrids of different origins.

Despite playing physiological roles in specific situations, DNA-RNA hybrids threat genome integrity. To investigate how cells do counteract spontaneous DNA-RNA hybrids, here we screen an siRNA library covering 240 human DNA damage response (DDR) genes and select siRNAs causing DNA-RNA hybrid accumulation and a significant increase in hybrid-dependent DNA breakage. We identify post-replicative repair and DNA damage checkpoint factors, including those of the ATM/CHK2 and ATR/CHK1 pathways. Thus, spontaneous DNA-RNA hybrids are likely a major source of replication stress, but they can also accumulate and menace genome integrity as a consequence of unrepaired DSBs and post-replicative ssDNA gaps in normal cells. We show that DNA-RNA hybrid accumulation correlates with increased DNA damage and chromatin compaction marks. Our results suggest that different mechanisms can lead to DNA-RNA hybrids with distinct consequences for replication and DNA dynamics at each cell cycle stage and support the conclusion that DNA-RNA hybrids are a common source of spontaneous DNA damage that remains unsolved under a deficient DDR.

Eating styles profiles in Chilean women: A latent Profile analysis.

The aims of this study were to identify profiles of women based on their levels of emotional, external and restraint eating, and to determine differences in these eating styles profiles based on nutritional status, sociodemographic characteristics, stress, social support, and satisfaction with the body image. Questionnaires were administered to 884 women aged 20 to 60 living in two Chilean cities. Questionnaires included the Dutch Eating Behavior Questionnaire (DEBQ), the Medical Outcomes Study-Social Support Survey, and the Perceived Stress Scale (PSS). Satisfaction with body image was assessed using a body-image-related single question. Nutritional status and sociodemographic characteristics were also assessed. Latent Profile Analysis (LPA) was used to identify profiles based on the three eating styles measured by the DEBQ. LPA allowed to distinguish four eating styles profiles: "women with medium emotional and external eating, high dietary restraint" (Profile 1, 36.64%); "women with low emotional, external and restraint eating" (Profile 2, 25.25%), "women with high emotional, external and restraint eating" (Profile 3, 21.85%); and "women with very low emotional and external eating, low dietary restraint" (Profile 4, 16.26%). Profile 1 had a greater proportion of women moderately satisfied with their body image. Profiles 2 and 4 scored higher in perceived social support and had greater proportions of women satisfied with their body image. Profile 4 had a higher proportion of married or cohabiting women. Profile 3 scored higher in the PSS and had higher proportion of obese and unsatisfied with their body image women. These results suggest that interventions to reduce emotional, external and restraint eating should not only involve the women, but also their family members.

[Diagnostic properties of case definitions of suspected COVID-19 in Chile, 2020Características diagnósticas das definições de caso suspeito de COVID-19 no Chile, 2020]. / Propiedades diagnósticas de las definiciones de caso sospechoso de COVID-19 en Chile, 2020.

OBJECTIVE: Compare the diagnostic properties of five case definitions of suspected COVID-19 that were used or proposed in Chile during the first eight months of the pandemic. METHODS: An analysis was done of the diagnostic properties (sensitivity, specificity, and positive and negative predictive values) of three case definitions of suspected COVID-19 used in Chile between March and October 2020, as well as two alternative proposed definitions. The sample was 2,019 people with known results for the polymerase chain reaction (PCR) test for SARS-CoV-2. Stepwise logistic regression was used to develop criterion 5, optimizing sensitivity and specificity values. Multifactor logistic regression was used to explore the association between demographic variables, symptoms and signs, and PCR positivity. Different positivity scenarios were analyzed and ROC curves were compared. RESULTS: The presence of anosmia (OR = 8.00; CI95%: 5.34-11.99), fever (OR = 2.15; CI95%: 1.28-3.59), and having been in close contact with a person sick with COVID-19 (OR = 2.89; CI95%: 2.16-3.87) were associated with a positive PCR result. According to the analysis of the ROC curve, criterion 5 had the highest capacity for discrimination, although there were no significant differences with the other four criteria. CONCLUSIONS: Criterion 5-based on anosmia, close contact with people with COVID-19, and fever as sufficient unique elements-was the most sensitive in identifying suspected cases of COVID-19, a key aspect in controlling the spread of the pandemic.

OBJETIVO: Comparar as características diagnósticas de cinco critérios das definições de caso suspeito de COVID-19 usados ou propostos no Chile nos oito primeiros meses de pandemia. MÉTODOS: Foram avaliadas as características diagnósticas (sensibilidade, especificidade e valores preditivos positivo e negativo) de três critérios das definições de caso suspeito de COVID-19 usados no Chile entre março e outubro de 2020 e de duas alternativas propostas para definição de caso. A amostra do estudo consistiu 2 019 pessoas com resultados conhecidos no exame de reação em cadeia da polimerase (PCR) para SARS-CoV-2. Para elaborar o critério 5, uma regressão logística com método stepwise foi realizada otimizando os valores de sensibilidade e especificidade. A associação entre variáveis demográficas, sintomas e sinais e resultado positivo no exame de PCR foi testada em um modelo de regressão logística multifatorial. Situações diferentes de resultado positivo foram testadas com uma análise comparativa das curvas ROC. RESULTADOS: Presença de anosmia (OR 8,00; IC95% 5,34­11,99), febre (OR 2,15; IC95% 1,28­3,59) e contato próximo anterior com uma pessoa com COVID-19 (OR 2,89; IC95% 2,16­3,87) foram associados a um resultado positivo no exame de PCR. De acordo com a análise das curvas ROC, o critério 5 demonstrou maior capacidade discriminatória, apesar de não existir diferença significativa com os outros quatro critérios. CONCLUSÃO: O critério 5 ­ presença de anosmia, febre e contato próximo com uma pessoa com COVID-19 como elementos únicos e suficientes ­ demonstrou maior sensibilidade para identificar casos suspeitos de COVID-19, o que é fundamental para controlar a disseminação da pandemia.

A Track Geometry Measuring System Based on Multibody Kinematics, Inertial Sensors and Computer Vision.

This paper describes the kinematics used for the calculation of track geometric irregularities of a new Track Geometry Measuring System (TGMS) to be installed in railway vehicles. The TGMS includes a computer for data acquisition and process, a set of sensors including an inertial measuring unit (IMU, 3D gyroscope and 3D accelerometer), two video cameras and an encoder. The kinematic description, that is borrowed from the multibody dynamics analysis of railway vehicles used in computer simulation codes, is used to calculate the relative motion between the vehicle and the track, and also for the computer vision system and its calibration. The multibody framework is thus used to find the formulas that are needed to calculate the track irregularities (gauge, cross-level, alignment and vertical profile) as a function of sensor data. The TGMS has been experimentally tested in a 1:10 scaled vehicle and track specifically designed for this investigation. The geometric irregularities of a 90 m-scale track have been measured with an alternative and accurate method and the results are compared with the results of the TGMS. Results show a good agreement between both methods of calculation of the geometric irregularities.

In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine.

Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and ß2 adrenoreceptor.

[Features of patients admitted for COVID-19 at a regional hospital in the Chilean Araucania Region]. / Características clínicas de pacientes ingresados por COVID-19 en un Hospital de alta complejidad de la región de la Araucanía-Chile.

BACKGROUND: The Araucania region in Chile had the greatest COVID-19 incidence and lethality in Chile Aim: To describe the clinical characteristics and evolution of patients admitted for COVID-19 in a high complexity Hospital in the region of La Araucanía-Chile. MATERIAL AND METHODS: Review of medical records of the first 169 patients aged 55 ± 17 years (50% women) admitted for COVID-19 between march and may, 2020 at a regional hospital in Temuco Chile. RESULTS: The most common comorbidities of these patients were hypertension, diabetes, and obesity. The symptom triad of cough, dyspnea and fever was present in 85%. Less frequent symptoms were diarrhea and vomiting. Biomarkers at admission such as ferritin, D-dimer, among others, were significantly higher among patients who required admission to the Intensive Care Unit. The presence of cough, dyspnea and fever were significantly associated with longer hospitalization time and requirement for mechanical ventilation. Hypertension and obesity were significantly associated with longer hospitalization stay. Eight percent of patients died. CONCLUSIONS: Symptoms such as cough, dyspnea and fever and specific biomarkers on admission were associated with a worse evolution of adult inpatients with COVID-19.

Gallbladder cancer who is really cured?

BACKGROUND: Although gallbladder cancer (GBCA) is characterized by a dismal prognosis, there is a proportion of patients who are cured. The aim of this study was to analyze the profile of these patients. METHODS: A database was queried for patients who underwent curative resection with a follow-up of at least 5 years. Patients were prospectively treated and registered by the same surgical team. A multivariate regression analysis was used to identify factors associated with long-term survival. RESULTS: From 1988 to 2013, 461 patients were evaluated and 112 who underwent resection were analyzed. Among the patients, five year survival was 57% while lymph node and liver compromise were the only independent factors associated with survival. On the other hand, the elapsed time between the cholecystectomy and the resection, the differentiation grade and the level of wall invasion did not have an independent effect on the prognosis. CONCLUSION: Despite its poor prognosis, a subset of patients can be cured of GBCA. R0 resection of patients without lymph and liver infiltration are key to GBCA survival.