[Overlooked somatic effects of serotoninergic antidepressants]. / Effets somatiques méconnus des antidépresseurs sérotoninergiques.

The mechanism of action of selective serotonin reuptake inhibitors (SSRI) is still not properly established. It is essential to consider their positive and negative side effects before prescribing. In this article, we describe several of these side effects in the context of common pathologies and clinical situations. We discuss their cardioprotective effect and their role in the functional recovery of patients following stroke. We recall the increase in the risk of bleeding when prescribing SSRI concomitantly with antiaggregating and anticoagulant treatments. Prescribing SSRI also increases the risk of fracture and the frequency of hyponatremia. In the context of COPD, the effects of SSRI are more difficult to establish.

Le mécanisme d'action des antidépresseurs inhibiteurs sélectifs de la recapture de la sérotonine (ISRS) n'est toujours pas formellement établi. Il est essentiel de prendre en compte leurs effets secondaires positifs et négatifs pour leur prescription. Dans cet article, nous décrivons plusieurs de ces effets dans le contexte de pathologies et situations cliniques courantes. Nous abordons leur effet cardioprotecteur ainsi que leur rôle dans la récupération fonctionnelle des patients à la suite des accidents vasculaires cérébraux. Nous rappelons la majoration du risque hémorragique lors de la prescription d'ISRS en concomitance de traitements antiagrégants et anticoagulants. La prescription d'ISRS augmente également le risque fracturaire et la fréquence d'une hyponatrémie. Dans le contexte de la bronchopneumopathie chronique obstructive, les effets d'un ISRS sont plus difficiles à établir.

Brain Metastases from Genito-Urinary Cancers in the Canton of Geneva (Switzerland): Study of Incidence, Management and Outcomes.

BACKGROUND: Incidence of brain metastases is precisely unknown and there is no clear consensus on their management. We aimed to determine the incidence of brain metastases among patients with genito-urinary primaries, present patients' characteristics and identify prognostic factors. METHOD: We identified 51 patients treated in Geneva University Hospitals between January 1992 and December 2019. We retrospectively correlated their overall survival with 23 variables. We repeated a multivariate analysis with significant variables. RESULTS: Overall incidence of Brain Metastases (BMs) among Genito-Urinary (GU) patients is estimated to be 1.76% (range per primary GU tumour type: 0.00-6.65%). BMs originate from germ cell tumours in two cases (3.92%), from urothelial cell carcinoma in 15 cases (29.41%), from prostate cancer in 13 cases (25.49%), and from renal cell carcinoma in 21 cases (41.18%); there are no BMs from penile cancer in our cohort. The median age at BM diagnosis is 67 years old (range: 25-92). Most patients (54%) have a stage IV disease at initial diagnosis and 11 patients (22%) have BM at initial diagnosis. Only six patients (12%) are asymptomatic at BM diagnosis. The median Overall Survival (OS) from BM diagnosis is 3 months (range: 0-127). Five patients (10%) are long survivors (OS > 24 months). OS is significantly influenced by patient performance status and administration of systemic treatment. In the absence of meningeal carcinomatosis, OS is influenced by systemic treatment and stereotactic radiosurgery. We also apply the Graded Prognostic Assessment (GPA) score to our cohort and note significant differences between groups. CONCLUSION: Brain metastases from solid tumours is not a uniform disease, with a prognosis varying a lot among patients. The optimal management for patients with genito-urinary malignancies with brain metastases remain unclear and further research is needed.

Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs. METHODS: Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114). RESULTS: The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS (p < 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort. CONCLUSIONS: The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit.