Identification of Lynch Syndrome Carriers among Patients with Small Bowel Adenocarcinoma

Lynch syndrome; Hereditary cancer; Small bowel adenocarcinomaSíndrome de Lynch; Cáncer hereditario; Adenocarcinoma de intestino delgadoSíndrome de Lynch; Càncer hereditari; Adenocarcinoma d'intestí primBackground: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families.This study was funded by the CERCA Program (Generalitat de Catalunya) and Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRPRE 2017SGR21, GRC 2017SGR653). CIBEREHD is funded by the Instituto de Salud Carlos III

Laparoscopic vs. Open Approach in Emergent Inguinal Hernia: Our Experience and Review of Literature

There is currently no consensus or homogeneous recommendation about the role of the laparoscopic approach in emergent inguinal hernia surgery. The aim of this manuscript is showing our experience and results of laparoscopic approach for emergent groin hernia repair comparing with open approach. A retrospective review of a prospectively maintained database between January 2011 and December 2021 of acute incarcerated groin hernia that were operated at Virgen del Rocio University Hospital. In this period, they were identified 463 patients with groin hernia that required an emergency repair. 454 patients underwent open surgery (group 1) and 36 patients underwent laparoscopic approach (TAPP procedure) (group 2). Median length stay was 1 day in lap group and 2 days in open approach. Reintervention was necessary in 20 cases (4.40%) from group 1 and one (2.27%) from group 2. In laparoscopic approach, no mortality was described but in open approach, 10 patients (2.20%) died. Globally, 58 cases (12.77%) from group 1 and six patients (16.66%) from group 2 presented any complication. Wound infection was higher in group of open repairs (5.94% vs. 2.77%). Non-surgical complications were higher in open approach (19 vs. 0). There is no statistical significance in any of these items. Laparoscopic approach is a safe, feasible and effective therapeutic option for the treatment of incarcerated groin hernia that require emergency surgery, but prospective and randomized comparative studies are needed to establish the best approach

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The Next America

Given the current political debates regarding the extent to which immigration impacts social, political, and economic change in the United States, the present study seeks to empirically test attitudes and emotions toward immigrants. The goal of this project is to test the extent to which anger produces outgroup derogation motives and fear produces ingroup protection motives as a function of perceived cultural change. In addition, we are interesting in understanding the degree to which anger and fear produce collective angst as a function of perceived cultural change caused by an influx of immigrants in the United States. Finally, we will explore the relationship between perceived cultural change and nostalgia

Cultural Inertia: Framework of Change and Intergroup Relations

Cultural change is theorized to generate intergroup hostility. Three experiments apply the Cultural Inertia Model to test the effects of change on intergroup relations. Two predictions of cultural inertia were tested: (a) cultures at rest tend to stay at rest and (b) individual difference variables function as psychological anchors. In static societies, perceived change leads to greater threat (Experiment 1), endorsement of anti-immigration legislation (Experiment 1), and collective angst (Experiments 1 and 2). Perceptions of change in static societies lead to more fear-related emotional reactions (Experiment 3). Framing cultural change as continuous rather than abrupt may be a solution for reducing negative reactions caused by cultural change (Experiments 2 and 3). Individual difference factors function as anchors that cement individuals in a state of uniformity (Experiments 2). The findings demonstrate that social interactions rely on perceptions toward change and individual difference factors that anchor one’s willingness to accept change

Using NS5B Sequencing for Hepatitis C Virus Genotyping Reveals Discordances with Commercial Platforms.

We aimed to evaluate the correct assignment of HCV genotypes by three commercial methods-Trugene HCV genotyping kit (Siemens), VERSANT HCV Genotype 2.0 assay (Siemens), and Real-Time HCV genotype II (Abbott)-compared to NS5B sequencing. We studied 327 clinical samples that carried representative HCV genotypes of the most frequent geno/subtypes in Spain. After commercial genotyping, the sequencing of a 367 bp fragment in the NS5B gene was used to assign genotypes. Major discrepancies were defined, e.g. differences in the assigned genotype by one of the three methods and NS5B sequencing, including misclassification of subtypes 1a and 1b. Minor discrepancies were considered when differences at subtype levels, other than 1a and 1b, were observed. The overall discordance with the reference method was 34% for Trugene and 15% for VERSANT HCV2.0. The Abbott assay correctly identified all 1a and 1b subtypes, but did not subtype all the 2, 3, 4 and 5 (34%) genotypes. Major discordances were found in 16% of cases for Trugene HCV, and the majority were 1b- to 1a-related discordances; major discordances were found for VERSANT HCV 2.0 in 6% of cases, which were all but one 1b to 1a cases. These results indicated that the Trugene assay especially, and to a lesser extent, Versant HCV 2.0, can fail to differentiate HCV subtypes 1a and 1b, and lead to critical errors in clinical practice for correctly using directly acting antiviral agents

Identification of Lynch Syndrome Carriers among Patients with Small Bowel Adenocarcinoma

Background: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families

Minor discordances (differences at the subtype level) from the three assayed commercial tests compared to NS5B DNA sequencing.

<p>Minor discordances (differences at the subtype level) from the three assayed commercial tests compared to NS5B DNA sequencing.</p