Sophia Genetics (France)

e13088 Background: CDK4/6i combined with ET is 1L standard of care treatment for HR+/HER2- for mBC patients, however duration of response varies with some patients experiencing disease progression within 12-months. Limited predictive factors related to ET+CDK4/6i treatment response exist. This pilot aims to assess the feasibility of developing a ML derived risk score for CDK4/6i+ET across 5 different data modalities to inform escalation and de-escalation therapeutic strategies. Methods: A pilot study on a retrospective cohort of 131 patients with mBC from the Memorial Sloan Kettering Cancer Center (MSK) treated with CDK4/6i and ET in the 1L setting was carried out to develop a ML based algorithm for predicting rwPFS at an individual patient level. Baseline multimodal data (including clinical, demographic, histopathological, genomic and radiomic) alongside clinical outcomes were collected. For radiomic analysis, up to 5 lesions were segmented in 3D on baseline PET/CT scans per patient using the SOPHiA DDMTM Radiomics platform. Radiomic features, extracted per IBSI standards, were combined with other data modalities. Baseline tumor genomic analysis was performed using the MSK-IMPACT assay, including genes with an alteration frequency > 5% in the cohort. A filter-based variable selection method was applied prior to training multiple ML algorithms, with the optimization criteria being the Brier score for rwPFS prediction. Due to the limited cohort size, a nested cross-validation approach was employed to ensure robust performance estimation. Results: A Random Forest survival model, combined with k-Nearest Neighbor (k-NN) imputation techniques for handling missing data, achieved an AUC of 0.787 (95% CI, 0.716–0.859) at 12 months for predicting rwPFS. Presence of liver metastases, SUVmax, total tumor volume, CEA, CA 15-3, TP53 mutation and PET uptake heterogeneity were among the top weighted features. These clinically plausible features, combined into a multimodal algorithm, allowed to stratify patients into two risk groups based on their predicted rwPFS with a median rwPFS of 45.2 (95% CI, 27.1-n/a) in low-risk vs 11.3m (95% CI, 9.1-16.1m) in high-risk group (hazard ratio: 4.10, 95% CI, 2.64–6.37). Conclusions: This pilot study demonstrates the feasibility of a ML, multimodal approach to predict rwPFS for patients with HR+/HER2- mBC treated with 1L CDK4/6i + ET. This approach could be implemented in the clinical setting to guide treatment choice and to inform clinical trial design by identifying high-risk individuals. Further training and validation of the model is planned in a larger, multicentric cohort.

In 1762, Louis-Antoine Marquis de Caraccioli (1719-1803), a prolific writer of the eighteenth century, dedicated a book to a psychological theme that medicine has forgotten: 'gaité' in French, which we will translate as 'cheerfulness'. At the beginning of the nineteenth century, this work inspired two doctoral theses in medicine, one defended in Montpellier, the other in Paris. In their texts, Louis Monferran (1785-?) and Vincent Rémi Giganon (1794-1857) explored the therapeutic benefits of the medical prescription of cheerfulness. In addition to lifestyle recommendations, they focused on the psychotropic substances available to them: alcohol, coca, hemp and opiates. In an original and novel way, Giganon introduced and recommended 'le gaz oxydule d'azote inspiré', or inhaled nitrous oxide gas.

Differentiating benign from malignant renal tumors is important for patient management, and it may be improved by quantitative CT features analysis including radiomic. This study aimed to compare performances of machine learning models using bio-clinical, conventional radiologic and 3D-radiomic features for the differentiation of benign and malignant solid renal tumors using pre-operative multiphasic contrast-enhanced CT examinations. A unicentric retrospective analysis of prospectively acquired data from a national kidney cancer database was conducted between January 2016 and December 2020. Histologic findings were obtained by robotic-assisted partial nephrectomy. Lesion images were semi-automatically segmented, allowing for a 3D-radiomic features extraction in the nephrographic phase. Conventional radiologic parameters such as shape, content and enhancement were combined in the analysis. Biological and clinical features were obtained from the national database. Eight machine learning (ML) models were trained and validated using a ten-fold cross-validation. Predictive performances were evaluated comparing sensitivity, specificity, accuracy and AUC. A total of 122 patients with 132 renal lesions, including 111 renal cell carcinomas (RCCs) (111/132, 84%) and 21 benign tumors (21/132, 16%), were evaluated (58 +/- 14 years, men 74%). Unilaterality (100/111, 90% vs. 13/21, 62%; p = 0.02), necrosis (81/111, 73% vs. 8/21, 38%; p = 0.02), lower values of tumor/cortex ratio at portal time (0.61 vs. 0.74, p = 0.01) and higher variation of tumor/cortex ratio between arterial and portal times (0.22 vs. 0.05, p = 0.008) were associated with malignancy. A total of 35 radiomics features were selected, and "intensity mean value" was associated with RCCs in multivariate analysis (OR = 0.99). After ten-fold cross-validation, a C5.0Tree model was retained for its predictive performances, yielding a sensitivity of 95%, specificity of 42%, accuracy of 87% and AUC of 0.74. Our machine learning-based model combining clinical, radiologic and radiomics features from multiphasic contrast-enhanced CT scans may help differentiate benign from malignant solid renal tumors.

Yawning is a fascinating physiological behaviour that has been poorly addressed except in old medical books. Whereas the purpose of this behaviour is still not clearly identified, the ancient authors made it a clinical symptom, especially a psychological one. After presenting some current notions about yawning, we review publications on yawning written by physicians, from antiquity to the twentieth century, and, in particular, those dealing with psychological and psychiatric aspects.

Non-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage and genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to introduce a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed with EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primary tumor (one before the TKI introduction and two after). An imaging biomarker based on evolution of texture heterogeneity between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker ([Formula: see text]). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant ([Formula: see text]). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.

Background
 In South Africa, seclusion is one of the practices used in the management of disruptive behaviors in psychiatric settings. Despite its continued use, seclusion is always subject to controversial debates, and patients who undergo it express a range of negative experiences.
 Objective
 To explore the experiences of patients regarding seclusion during their admission in a psychiatric hospital. Methods
 A qualitative descriptive design was used. In-depth interviews were conducted with ten patients attending a community psychiatric clinic in KwaZulu-Natal. Interviews were analyzed using content analysis.
 Results
 Two themes emerged from the findings: controversial views of seclusion and negative experiences of seclusion. Seclusion was considered more as a punishment measure which was often used abusively, than a therapeutic intervention. Participants expressed loneliness, humiliation, and powerlessness following their seclusion experience. Limited patient-staff interaction and communication worsened patients’ negativity towards seclusion. Conclusion
 Findings from this study underscore the need to review practices, policies and procedures regarding the use of seclusion. Seclusion should be only used when the need is absolute and as the last treatment option. Open communication between the care providers and the patients should be emphasized during the time of seclusion.
 Rwanda J Med Health Sci 2020;3(3):342-361

Abstract Background Whilst euthanasia and assisted suicide are forbidden by French Law, patients at the end of life, hospitalized in Palliative Care Units, sometimes express the Wish to Hasten their Death. Few Studies have analyzed the formulation of these patient requests in interviews and the associated death-related representations. The DESA study analyzed the expression of patients’ requests, focusing on the terms and how patients worded their wishes. The aim is to identify from the “raw wording” of the patients’ requests, the means of expressing them in all its singularity and evolution. Methods This is a qualitative study that took place in 11 French Palliative care Units during on year and included adult patients who had made an explicit request (euthanasia or physician assisted suicide) to a health care provider. Semi-structured interviews were conducted within 48 hours of the initial request (D0), then a week later (D7). Results At DO, the initial request is a request for euthanasia and it calls a third person urgently. This request is related to physical and psychological suffering, trauma and representations of death. At D7, we observe a semantic change; the request is less explicit and requires less intervention by a third party. The quest remains that of a death without suffering. Conclusions These patients express themselves easily on their request and listening is necessary to be able to hear the meaning of the words but also their functions. It is their nuance, variety and evolution that help to understand what the requirements mean. Trial registration number : ClinicalTrials.gov Identifier: NCT02845817

(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.