[Incidence, characteristics and survival of patients with pneumocystis pneumonia in solid oncology]. / Incidence, caractéristiques et survie des patients présentant une pneumocystose en oncologie solide.

INTRODUCTION: Pulmonary pneumocystis causes interstitial lung disease, particularly in patients with solid cancers. The aim of this study is to clarify its incidence, which remains poorly understood, and to identify patients at risk and prognostic factors. METHODS: Data on patients with solid tumors and pulmonary pneumocystis were retrospectively collected from January 1, 2014 to December 31, 2019 in two hospitals in Rennes. Incidence was estimated via the Poisson model. Survival data were estimated using Kaplan-Meier method and Log-rank test. A multivariate Cox model was performed to identify risk factors for death. RESULTS: The incidences of pulmonary pneumocystis in metastatic cancer patients receiving parenteral systemic therapy are 198 and 349 cases per 100,000 patients per year in these two centers, respectively. Most patients were being treated with corticosteroids and chemotherapy at the time of pulmonary pneumocystis. The mortality rate for patients with pulmonary pneumocystis is 38%. Median overall survival was 2,7 months. Risk factors for death are corticotherapy greater than 20mg, prednisone equivalent, daily and chemotherapy. DISCUSSION: Pulmonary pneumocystis pneumonia is rare but not exceptional and has a poor prognosis in solid oncology. It frequently occurs in patients treated with long-term corticosteroids. Oncologists need to be better informed to discuss prophylaxis whenever corticosteroids are prescribed for several weeks.

Chemotherapy with or without selective internal radiation therapy for intrahepatic cholangiocarcinoma: Data from clinical trials.

BACKGOUND AND AIMS: In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT. APPROACH AND RESULTS: We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses. CONCLUSIONS: This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.

Evolution of parenteral nutrition practices in a comprehensive cancer center: Comparative audits.

INTRODUCTION: Malnutrition affects 20% to 70% of oncology patients depending on the patient's age, type and stage of cancer. Two audits were carried out in 2016 and 2019 to evaluate the practice of Parenteral Nutrition (PN). METHODS: Records of adult medical inpatients who received PN between January 1, 2018 and April 30, 2019 were retrospectively analysed. Twenty criteria were defined. We conducted a statistical analysis to compare the two audit data. RESULTS: Between January 1, 2018 and April 30, 2019, 86 hospitalizations with a PN prescription were analysed. Of the 69 patients, 66% were female, the mean and median age was 60 years. These were most often medical oncology patients in palliative care. Gynecological and digestive tumors were the two main tumor localization. Bowel obstruction and palliative care management were the two main reasons for hospitalization. Nutritional assessment, amount of energy prescribed, monitoring, and duration of PN remain with poor results. CONCLUSION: Our study seems to show improvements in the relevance of PN indications, the prescription, and monitoring in patients due to the computerization of prescription and training of professionals. PN remains often prescribed in exclusive palliative situations. We need to continue our improvements, particularly for the initial clinical and biological assessment, and the monitoring. It requires a referral team to improve management of patients treated with PN.

Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors.

Adverse effects have limited the clinical use of telithromycin. Preferential inhibition of the nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (α3ß2 and NMJ), the ciliary ganglion of the eye (α3ß4 and α7), and the vagus nerve innervating the liver (α7) could account for the exacerbation of myasthenia gravis, the visual disturbance, and the liver failure seen with telithromycin use. The studies presented here enable the prediction of expected side effects of macrolides in development, such as solithromycin (CEM-101).

The adult rat hippocampal slice revisited with multi-electrode arrays.

The multi-electrode arrays (MEA) technology for the recording of brain slices is available for more than 10 years. However, despite its relative simplicity, this recording technique is not widely used in academic or pharmaceutical research laboratories. We illustrate here that MEA provide multiple possibilities to investigate some network physiological properties as well as to evaluate the pharmacological effects of compounds. We first document that MEA allow to trigger and to record conventional FP which are inhibited by the block of action potential propagation (with 500 nM TTX). FP recorded with MEA are sensitive to ionic substitutions, to ionotropic glutamate receptor antagonists (CNQX or NBQX) and to energetic failure. Second, we illustrate that different "classical" protocols (paired-pulse, LTP, chemical LTD), revealing synaptic plasticity mechanisms, could be performed. Third, we document that MEA allow spatial and temporal discriminations for the effects of known pharmacological compounds such as competitive antagonist (gabazine, bicuculline) and allosteric modulators (steroids) of GABA(A) receptors. In conclusion, we illustrate that MEA recordings of adult rat hippocampal slices constitute a powerful and sensitive system to evaluate the effect of molecules on basic synaptic propagation/transmission and on synaptic plasticity processes.