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It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT.

It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT. [ABSTRACT FROM AUTHOR]

Abstract Background To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of Staphylococcus aureus with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted S. aureus proteome. Results In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over-expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper-mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides. Conclusion Our proteome and transcriptome analyses have been performed during stationary-phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected in vitro. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations during a complex antibiotic resistance mechanism but also unravels potential drug targets or markers that are constitutively expressed by resistant strains regardless of their genetic background, amenable to be used as diagnostic targets.

An abstract is offered of a research paper on beta lactamase producing gramnegative organisms in patients in Switzerland by J. Pasricha and colleagues, presented at the International Conference on Prevention & Infection Control (ICPIC 2011) held in Geneva, Switzerland on June 29-July 2, 2011.

Gastric cancer often presents at an advanced stage in Western populations due to a lack of screening programs, leading to poor prognoses. Historically, palliative chemotherapy resulted in a median survival of 9.9 months. However, the introduction of the FLOT regimen and immunotherapy has significantly altered treatment outcomes. Oligometastatic gastric cancer, defined as metastasis limited to a single organ or a few sites, has emerged as a distinct subgroup with improved survival when treated with a combination of systemic and local therapies. We present the case of a 54-year-old male patient diagnosed with microsatellite-stable (MSS) oligometastatic gastric adenocarcinoma, including liver and peritoneal metastases, who achieved a complete pathological response following neoadjuvant chemoimmunotherapy with FOLFOX and nivolumab. Despite unfavorable prognostic factors, such as liver involvement and positive peritoneal cytology, the patient responded well to the treatment, allowing curative surgery. Postoperative histology confirmed complete regression of both the primary tumor and metastases, with no recurrence observed at the 1-year follow-up. This case shows the potential of combined chemoimmunotherapy to convert previously inoperable MSS gastric cancer to surgical candidates. Further research is needed to better define patient selection criteria and assess long-term outcomes for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mechahougui, Chevallay, Cauchy, Chaveau, Puppa, Koessler and Monig.)

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer., Methods: A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including "Peritoneal carcinomatosis", "Peritoneal metastasis", "PIPAC", "Pressurized intraperitoneal aerosol chemotherapy" and "Colorectal cancer". Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded., Results: A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales., Conclusions: PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials.

Enabling the examination of cell-cell relationships in tissue, spatially resolved omics technologies have revolutionised our perspectives on cancer biology. Clinically, the development of immune checkpoint inhibitors (ICI) has advanced cancer therapeutics. However, a major challenge of effective implementation is the identification of predictive biomarkers of response. In this review we examine the potential added predictive value of spatial biomarkers of response to ICI beyond current clinical benchmarks., (© 2024. The Author(s).)

Objective: To determine whether a brief educational intervention for Junior Medical Officers (JMOs), using teaching methods aimed at achieving higher outcomes on Bloom's Taxonomy, significantly improved participant confidence and knowledge in decision making about restrictive care., Method: JMOs received a teaching session on restrictive medical and mental health care. Groups were randomly assigned to either sessions including a component of modern pedagogical interventions (Think-Pair-Share and SNAPPS), or sessions including a control period focusing on reviewing a condensed summary of relevant information. Pre- and post-intervention measures were recorded for subjective self-ratings of confidence and scores on standardized clinically relevant extended matching questions (EMQs)., Results: There was no difference in subjective confidence improvement between groups; however, the group receiving the modern pedagogical intervention demonstrated significantly greater objective performance on knowledge-based EMQs., Conclusions: A brief modern pedagogical intervention using interactive teaching methods shows promise for improving knowledge of restrictive care and the Mental Health and Guardianship Acts. In the control group, similarly increased confidence in knowledge did not equate to increased competence on a knowledge assessment. Refurbishing educational interventions presents opportunities for improving clinical outcomes and engaging junior doctors in psychiatry., Competing Interests: DisclosureThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The management of localized rectal cancer has evolved significantly over the last two years. On one hand, intensification of treatments (radio-chemotherapy, chemotherapy, then surgery) for the most advanced tumors has shown an improvement in clinical results compared to less intense regiments. On the other hand, the possibility, as for prostate cancers, of opting for active surveillance without surgery in patients presenting a complete clinical response after a treatment phase, is now accepted. More recently, the Swiss recommendations for the surveillance of rectal cancer have been modified and now differ from those of colon cancers, by incorporating pelvic MRI and rectoscopy in addition, as well as special guidelines for tumors under active surveillance., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background and study aims Optical diagnosis poses challenges to implementation of "resect and discard" strategies. This study aimed to assess the feasibility and performance of a new commercially available system for colorectal polyps. Patients and methods Nine expert endoscopists in three centers performed colonoscopies using artificial intelligence-equipped colonoscopes (CAD EYE, Fujifilm). Histology and predictions were compared, with hyperplastic polyps and sessile serrated lesions grouped for analysis. Results Overall, 253 polyps in 119 patients were documented (n=152 adenomas, n=78 hyperplastic polyps, n=23 sessile serrated lesions). CAD EYE detected polyps before endoscopists in 81 of 253 cases (32%). The mean polyp size was 5.5 mm (SD 0.6 mm). Polyp morphology was Paris Ip (4 %), Is (28 %), IIa (60 %), and IIb (8 %). CAD EYE achieved a sensitivity of 80%, specificity of 83%, positive predictive value (PPV) of 96%, and negative predictive value (NPV) of 72%. Expert endoscopists had a sensitivity of 88%, specificity of 83%, PPV of 96%, and NPV of 72%. Diagnostic accuracy was similar between CAD EYE (81%) and endoscopists (86%). However, sensitivity was greater with endoscopists as compared with CAD EYE ( P <0.05). CAD EYE classified sessile serrated lesions as hyperplasia in 22 of 23 cases, and endoscopists correctly classified 16 of 23 cases. Conclusions The CAD EYE system shows promise for detecting and characterizing colorectal polyps. Larger studies are needed, however, to confirm these findings., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)