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BackgroundThe selection of patients for genetic testing to rule out Lynch syndrome is currently based on fulfilment of at least one of the revised Bethesda criteria followed by mismatch repair (MMR) status analysis. A study was undertaken to compare the present approach with universal MMR study-based strategies to detect Lynch syndrome in a large series of patients with colorectal cancer (CRC).Methods2093 patients with CRC from the EPICOLON I and II cohorts were included. Immunohistochemistry for MMR proteins and/or microsatellite instability (MSI) analysis was performed in tumour tissue. Germline MLH1 and MSH2 mutation analysis was performed in patients whose tumours showed loss of MLH1 or MSH2 staining, respectively. MSH6 genetic testing was done in patients whose tumours showed lack of MSH6 expression or a combined lack of MSH2 and MSH6 expression but did not have MSH2 mutations. PMS2 genetic testing was performed in patients showing isolated loss of PMS2 expression. In patients with MSI tumours and normal or not available MMR protein expression, all four MMR genes were studied.ResultsA total of 180 patients (8.6%) showed loss of expression of some of the MMR proteins and/or MSI. Four hundred and eighty-six patients (23.2%) met some of the revised Bethesda criteria. Of the 14 (0.7%) patients who had a MMR gene mutation, 12 fulfilled at least one of the revised Bethesda criteria and two (14.3%) did not.ConclusionsRoutine molecular screening of patients with CRC for Lynch syndrome using immunohistochemistry or MSI has better sensitivity for detecting mutation carriers than the Bethesda guidelines.

BackgroundEven if the use of stent as bridge to surgery (BTS) for obstructive colon cancer was described long ago, there is still much controversy on their use. Patient recovery before surgery and colonic desobstruction are just some of the reasons to defend this management that can be found in several available articles.MethodsThis is a single-center, retrospective cohort study, including patients with obstructive colon cancer treated between 2010 and 2020. The primary aim of this study is to compare medium-term oncological outcomes (overall survival, disease-free survival) between stent as BTS and ES groups. The secondary aims are to compare perioperative results (in terms of approach, morbidity and mortality, and rate of anastomosis/stomas) between both groups and, within the BTS group, analyze whether there are any factors that may influence oncological outcomes.ResultsA total of 251 patients were included. Patients belonging to the BTS cohort presented a higher rate of laparoscopic approach, required less intensive care management, less reintervention, and less permanent stoma rate, when comparing with patients who underwent urgent surgery (US). There were not significant differences in terms of disease-free survival and overall survival between the two groups. Lymphovascular invasion negatively affected oncological results but was not related with stent placement.ConclusionThe stent as a bridge to surgery is a good alternative to urgent surgery, which leads to a decrease in postoperative morbidity and mortality without significantly worsening oncological outcomes.

Two thematic lines: the omnipresence of the theme of the maritime voyage in Portuguese culture--which Antonio Quadros calls the 'myth of Henry',--and its inflections in literature, more specifically, in Camoes's The Lusiads (Os Lusiadas) and Fernao Mendes Pinto's Pilgrimage (Peregrinagao) were examined. Thus, we focus on the state of the art about the topic of Henryism/the maritime voyage, taking into account the perspective of today's Portuguese scholars, and we look at how this theme is expressed in The Lusiads and Pilgrimage, thereby proving that these Renaissance works remain vital for the actual imaginary of the Portuguese people. Keywords: Pilgrimage; The Lusiads; Luis de Camoes; Fernao Mendes Pinto; Portuguese mythogenesis; Henry's myth; maritime voyage; travel literature

In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

Antibiotic consumption (AC) is a key component of antimicrobial stewardship programs to recognize local patterns of antibiotic use. Our aim was to measure AC in neonatal units, including neonatal (NICU)/paediatric (PICU) intensive care units in different countries. We conducted a multicenter, retrospective, cohort study in three NICUs, one neonatal ward, and three PICUs with a total of 84 beds. Global and individual AC in days of therapy (DOT) and DOT per 1000 patient-days were assessed. During the study period, 2567 patients were admitted, corresponding to 4961 patient-days in neonatal units and 9243 patient-days in PICUs. Multidrug-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus were more frequent in Brazil than in Germany. Average AC was 386.5 and 1335.5 DOT/1000PD in German and Brazilian neonatal units, respectively. Aminopenicillins plus 3rd generation cephalosporins were the most commonly prescribed antibiotics in German neonatal units, while aminopenicillins plus aminoglycosides were the class most commonly used in Brazilian NICU. Average AC was 888.1 and 1440.7 DOT/1000PD in German and Brazilian PICUs, respectively. Antipseudomonal penicillins were most commonly used in the German PICU, and glycopeptides were the most frequently prescribed in Brazilian PICUs. Carbapenems represented 2.3–14% of total DOTs in German neonatal units and 4% in the Brazilian NICU and 13.0% in the German PICU and 6–12.2% in Brazilian PICUs. We concluded that different patterns of most commonly prescribed antibiotics were observed in neonatal units and PICUs in these two countries, probably related to different local patterns of antibiotic resistance, with a higher antibiotic consumption in Brazilian study units.

Vitorino Nemésio (1901-1978), appartenant a la génération de la revue Presence, est connu par la production littéraire multiforme, ce qui comprend l'œuvre écrite en français La Voyelle Promise. Dans ce livre du poete portugais, le dialogue avec la France s'établit dans le plan linguistique et culturel et, sans doute, y est construite une image, une representation de l'autre. La connaissance du moi permet de mieux accéder a l'autre, et la connaissance de l'autre opere une clarification du moi. Plus que l'assimilation ou l'influence - a laquelle le poete ne peut pas échapper - en lisant l'œuvre, on perçoit la reconnaissance de l'altérité, d'une pratique culturelle différente qui est une présence étrangere dans l'imaginaire de l'écrivain. Le but de cette étude est celui de prouver que dans La Voyelle Promise de Vitorino Nemésio une image de la France est construite a la suite de la rencontre de l'identité avec l'altérité et que ce livre de poemes en français est une expression emblématique de l'interculturalité.

Background: Clinical trials have demonstrated the efficacy and safety of ustekinumab in Crohn’s disease (CD). However, more data are necessary on the effectiveness of ustekinumab in bio-naïve patients in real-life studies. Objectives: The aim of our study was to evaluate the effectiveness and safety of ustekinumab in patients with CD refractory or intolerant to conventional therapy and without previous exposure to biological drugs. Design: We performed a nationwide, observational, retrospective, multicentre study including patients with CD, in which ustekinumab was used as the first biological drug. Methods: The corticosteroid-free clinical and biological response and remission were analysed at weeks 16, 24, 52 and 72. Clinical remission was defined as Harvey–Bradshaw index ⩽ 4 and biological remission as a faecal calprotectin (FC) <250 mg/g and C-reactive protein (CRP) <5 mg/L. Moreover, the persistence of the treatment and any adverse events were assessed. Results: In all, 84 patients were included in the study, males and females were equally distributed, with a median age of 63 years [interquartile range (IQR): 51–75] and a median disease duration of 6.8 years [IQR: 3.6–17.0]. The majority (86.9%) of patients were treated with ustekinumab as monotherapy, without concomitant immunosuppressive medication. The proportion of patients in corticosteroid-free clinical remission or response at weeks 16, 24, 52 and 72 was 93.3% (56/60), 86.8% (46/53), 82.2% (37/45) and 71.4% (30/42), respectively. CRP returned to normal values in 47.6%, 43.2%, 50% and 52.4% of patients at weeks 16, 24, 52 and 72, respectively. Similarly, FC was normalized in 45.5%, 45.5%, 48.6% and 50% of patients at weeks 16, 24, 52 and 72, respectively. The cumulative probability of remaining on ustekinumab treatment was 84.8% (95% confidence interval: 73.3–91.6) after 72 weeks. Ustekinumab was discontinued in 10 patients (11.9%) within 72 weeks of follow-up. Reasons for discontinuing treatment were lack of response (n = 4), adverse events (n = 4) and death (n = 2). There were no discontinuations because of stable remission. Conclusions: Ustekinumab was effective and safe in Spanish bio-naïve CD patients, showing a quicker and more durable response than obtained in patients with previous biological treatment. In this cohort of bio-naïve patients starting on ustekinumab, the average age was high. Plain language summary Effectiveness and safety of ustekinumab in Crohn’s disease patients not previously exposed to other biological therapies Evidence on the use of ustekinumab in biological naïve real-world patients is scarce. Here, we present real-world data evaluating the effectiveness and safety of ustekinumab in 84 bio-naïve patients from 17 Spanish hospitals. We report high rates of both clinical and biological remission. Moreover, after 1 year, 90.4% of patients remained being treated with ustekinumab. The safety profile of ustekinumab in these patient population was favourable. In conclusion, our results show that in patients with CD, ustekinumab could be considered as first-line therapy.

Partindo de uma metodologia qualitativa de base documental, analisa-se a bibliografia ativa, designadamente, o romance Ensaio sobre a cegueira de José Saramago, abarcando-se igualmente outras modalidades genológicas do autor, textos de diversos tipos, sobretudo entrevistas, justapondo e revisitando o parecer autoral dentro de um recorte que pretende evidenciar a figura do cão das lágrimas como personagem de sentimentos e valores humanos. A revisitação da obra Ensaio sobre a cegueira segundo este prisma conduz-nos a uma reflexão sobre função da escrita e do escritor José Saramago que se demarca de todos aqueles que, inspirados na polémica expulsão dos poetas da República ideal por parte de Platão, associavam a poesia à imoralidade ou à inutilidade. Ao invés, a escrita saramaguiana aproxima-se do pensamento dos escritores que fazem a apologia da criação literária, tendendo a considerá-la como uma parte ou um instrumento da filosofia moral. Com base no exposto, este artigo pretende contribuir para sistematizar o conceito de homem e de mundo para José Saramago, através da figura do cão enxuga-lágrimas, que se apresenta em conformidade com o pensamento do autor textual e empírico no tocante a valores humanistas como a fraternidade e a igualdade, em defesa lucidez e da liberdade. Using a qualitative, documentary-based methodology, the active bibliography is analyzed, namely, the novel Ensaio sobre a cegueira by José Saramago. We also focus on other genological modalities of the author, texts of different types, especially interviews, to revisit the authorial opinion on the figure of the dog of tears. This dog is a character of human feelings and values. The analysis of the work Ensaio sobre a cegueira according to this prism leads to a reflection on the function of writing and the writer José Saramago. The author thinks that literary creation as a part or an instrument of moral philosophy. Based on the above, this article aims to contribute to systematize the concept of man and the world for José Saramago, through the figure of the dog wipes tears. This dog is a projection of the textual and empirical author’s thinking, with regard to humanist values: fraternity and equality, in the defense of lucidity and freedom.

The intragastric balloon is a temporary treatment for obese patients. Fluid-filled devices have shown efficacy and safety, and are widely used. Recently, although there are no comparative studies between them, an air-filled balloon, Heliosphere® bag, has been proposed. Prospective, double-blind study in 33 patients with morbid and type 2 obesity: 23 female, 43.9 ± 10 years, 120.3 ± 17 kg, and body mass index (BMI) of 44.2 ± 5 kg/m 2 , placing 18 gastric balloons filled with 960 cm 3 of air (Heliosphere® bag) or 15 balloons filled with 700 ml of saline (Bioenterics-BIB®). Both balloons were placed with conscious sedation and removed under general anesthesia 6 months later. Intravenous drugs were given to control symptoms for 48 h. Patients were sent home on a 1000-kcal diet, multivitamin supplements, and oral proton pump inhibitors, and were followed monthly. Complications, symptoms, weight, and quality of life evaluated by the Gastrointestinal Quality of Life Index (GIQLI) scale were recorded. At 6 months, mean weight loss (12.8 ± 8 vs 14.1 ± 8 kg), BMI loss (4.6 ± 3 vs 5.5 ± 3 kg/m 2 ) and percent excess weight loss (27 ± 16 vs.30.2 ± 17) showed no significant differences between both groups. At removal, two Heliosphere® bags were not found in the stomach, and four patients required extraction of the balloon by rigid esophagoscopy or surgery ( p  = 0.02). Tolerance was good in both groups, but early removal occurred in three BIB® (20%) due to vomits and dehydration. The GIQLI total scores remained unchanged. Both balloons achieve a significant weight loss with good tolerance in obese patients. Nevertheless, Heliosphere® bag has severe technical problems that need to be solved before recommending it.

The focus of this study is an approach from the sociocultural and literary-historical point of view of the \"Carta de Achamento do Brasil\", written by Pero Vaz de Caminha to King D. Manuel I of Portugal. In addition to highlighting the first impressions of the Portuguese with the new place and its inhabitants, the present paper also explores the intentions of the Crown over the territory and the power dynamics announcing the exploratory intention of Brazil, confirmed by the subsequent colonization. Investigating the view of the \"Other\" and the discourse of Caminha around the views constructed about the female body, this paper addresses the impressions on women, nudity, the reading of the body, and its imbrications in sexuality. The authors, finally, aim to reflect on how the \"Letter\" may offer elements for understanding the image of Brazilian woman in the male imaginary of the Portuguese. O foco deste estudo é uma abordagem do ponto de vista sociocultural e histórico-literário da \"Carta de Achamento do Brasil\", escrita por Pero Vaz de Caminha ao rei D. Manuel I de Portugal. Além de se destacarem as primeiras impressões dos portugueses com o novo lugar e os seus habitantes, evidenciam-se igualmente as intenções da Coroa sobre o território e as relações de poder anunciadoras da intenção exploratória do Brasil, confirmada pela colonização posterior. Perspectivando a visão do \"Outro\" e analisando o discurso de Caminha em torno dos olhares construídos sobre o corpo feminino, visam-se abordar neste artigo aspectos como as impressões sobre a mulher, a nudez, a leitura do corpo e suas imbricações na sexualidade. Visa-se, enfim, refletir sobre o modo como a \"Carta\" pode oferecer elementos para a compreensão da imagem da mulher brasileira no imaginário masculino português.