Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

[Introduction to debriefing for internists: how to transform real or simulated clinical situations into learning moments]. / Initiation au débriefing pour les internistes : état des connaissances et mise en pratique pour transformer des situations cliniques réelles ou simulées en moments d'apprentissage.

Debriefing is a phase of synthesis and reflection that immediately follows a real-life or simulated situation. It is an essential educational step that forces the learners to reflect upon the thought processes that underlie their actions. Debriefing encourages a personal and collective reflection in order to remodel erroneous mental schemas and rectify actions done in context. Debriefing cannot be improvised; it requires a sound structure and regular practice in order to be truly effective. The debriefer must be considerate, choose appropriate learning objectives and dedicate ample time to the learners. Debriefing is focused on learning acquired in context-in other words, on the actions that were performed within a real-life or simulated clinical practice situation-and immediately follows the situation. After an initial phase of emotional release, the debriefer will help learners analyse their actions to identify their underlying rationale (contextualization), extract the overarching principles related to the lived situation in order to modify the rationale if needed (decontextualization) and assist the transfer of learning to real life (in the case of simulation) and to similar situations (recontextualization). A final summary of learning achieved during the training session concludes the debriefing. Debriefing is useful in any learning situation, including in internal medicine. Even if simulation is still underused in internal medicine, post-event debriefing can be implanted in our clinical services. Indeed, training our students and shaping them into healthcare professionals rest in no small part on hospital rotations where the intern is confronted with real-patient situations that are suitable to learning. Some in-hospital clinical encounters can be actively transformed into learning opportunities thanks to post-event debriefing, but can also passively morph into bad daily practice if no supporting action is implemented. Debriefing can thus provide an opportunity to develop non-technical skills in critical situations, or doctor-patient communication skills, within a team or between colleagues. These competencies are the hallmark of well-trained interns and are indispensable for the proper functioning of a care team. We will not develop the emotional and psychological management of debriefing in this article. We hope we will helpfully introduce as many of our colleagues as possible to the art of debriefing in most circumstances.

[Simulation in healthcare in North America: update and evolution after two decades]. / La simulation en santé en Amérique du Nord: état actuel et évolution après deux décennies.

OBJECTIVE: Update on simulation-based education and its evolution in North America. DATA SOURCES: Main articles including those published within the last five years and indexed in Medline, and unpublished data from the Royal College of Physicians and Surgeons of Canada have been analyzed. DATA SYNTHESIS: After a review of historical development of simulation in North America, this article draw the place of simulation in healthcare, for medical education, research and assessment. Funding and accreditation of simulation centres are also discussed. CONCLUSION: Simulation is fully integrated in healthcare in North America and represents one of the main elements for healthcare professional education. Simulation is also a symbol of excellence for health and teaching institutions. The evolution of simulation in North America is likely to inform the future of simulation in France.

[Validation of a clinical prediction rule for the diagnosis of deep vein thrombosis of the lower limbs in primary care]. / Validation d'un score de prédiction clinique de la thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

PURPOSE: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination. PATIENTS AND METHODS: Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2). RESULTS: Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study. CONCLUSIONS: This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.

[Quantitative assessment of medical students' clinical practical learning in department of obstetrics and gynecology of Brest Hospital University]. / Évaluation quantitative de l'enseignement pratique des étudiants hospitaliers en gynécologie-obstétrique au CHU de Brest.

OBJECTIVE: The main objective of this study was to describe how medical students got progressively trained to perform the most frequent medical procedures in obstetrics and gynecology. The secondary objective was to rationalize and plan the training. METHODS: The medical students in our University Hospital were contacted either directly or by e-mail. They were given an anonymous simple choice questionnaire relating to eight most important acts in the specialty. RESULTS: Three hundred and eighty-two medical students have been consulted. We got 173 answers which means a participation rate of 45.3%. The survey showed up that the considered procedures were progressively put into practice with the exception of two: the insertion of an intrauterine contraceptive device (coil) and of an implant. CONCLUSION: The study showed off some insufficiency in the training in two of the considered procedures. An amendment was proposed with simulated performances of the acts and the setting up of a training course booklet.

[Fatal outcome of an hydrogen sulfide poisoning]. / Intoxication accidentelle mortelle par hydrogène sulfuré.

We report a case of fatal outcome poisoning by massive exposure to hydrogen sulfide of a sewer worker. This rare event was associated with a moderate intoxication of two members of the rescue team. The death was due to asystole and massive lung oedema. Autopsy analysis showed diffuse necrotic lesions in lungs. Hydrogen sulfide is a direct and systemic poison, produced by organic matter decomposition. The direct toxicity mechanism is still unclear. The systemic toxicity is due to an acute toxicity by oxygen depletion at cellular level. It is highly diffusable and potentially very dangerous. At low concentration, rotten egg smell must trigger hydrogen sulfide suspicion since at higher concentration it is undetectable, making intoxication possible. In case of acute intoxication, there is an almost instantaneous cardiovascular failure and a rapid death. Hydrogen sulfide exposure requires prevention measures and more specifically the use of respiratory equipment for members of the rescue team.