ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.

[Complications of coronary invasive procedures in nonagenarians: A case-control study]. / Complications des procédures invasives coronaires chez les nonagénaires : une étude cas-témoins.

INTRODUCTION: Coronary heart disease is the leading cause of morbidity and mortality in nonagenarians, whose numbers have doubled in twenty years. In the absence of recommendations, the place of coronary invasive strategy in this population remains a therapeutic challenge and its interest as well as its risks are poorly established. The aim of our study was to evaluate the safety of coronary invasive practice in the nonagenarian population for all indications. POPULATION AND METHODS: This was a monocentric case-control study conducted from January 1, 2010 to May 30, 2019. The patients included were all nonagenarians who had undergone coronary angiography at the centre hospitalier de Troyes during this period. For each patient included, two controls matched on sex, date of procedure and procedure were drawn at random. The main judgment criterion was the occurrence of immediate per- or post-procedure complications during the stay in which the procedure was performed. The main secondary outcome measures were average length of stay, occurrence of intercurrent events during the stay (nosocomial infections, confusional syndrome), and loss of autonomy. RESULTS: In all, 59 nonagenarians and 118 controls were included in our study. We identified 30.5% major complications in the nonagenarians versus 10.2% in the controls (P=0.001; OR=0.26 [0.1-0.6]), with a significant difference in the occurrence of cardiogenic shock (P=0.04), heart failure (P=0.02) and ventricular rhythm disorders (P=0.04). Post-procedure acute renal failure was greater in the nonagenarians (P=0.02; OR=0.20 [0.05-1.57]). The mean length of stay was on average twice as long in the nonagenarians. CONCLUSION: Nonagenarian patients are subject to more complications when undergoing coronary invasive procedures compared to patients under 75.

[Impact of a Home Return Assistance Service (PRADO-IC) on the re-hospitalisation rate for heart failure patients]. / Étude de l'impact d'un service d'aide au retour à domicile (PRADO-IC) sur le taux de réhospitalisation des patients insuffisants cardiaques.

BACKGROUND: Heart failure is a public health problem. Since 2013, the National Insurance has been offering the PRADO-IC service for the return home of patients hospitalised for cardiac decompensation. The aim of this study was to assess the impact of PRADO on the rate of re-hospitalisation of patients with heart failure at the centre hospitalier de Troyes (CHT). MATERIAL AND METHODS: This was a 26-month monocentric retrospective study. Patients who were hospitalised for congestive heart failure in the cardiology department of the Troyes Hospital Centre from January 1, 2017 to August 31, 2018, and discharged home with the PRADO-IC service were included in the study. The primary outcome was the assessment of the number of readmissions for heart failure, 6 months before and 6 months after inclusion in the program. Secondary outcomes were the evaluation of the number of all-cause readmissions, the average length of stay and the time to readmission. RESULTS: The average number of hospitalisations for cardiac decompensation before inclusion in the PRADO decreased from 0.34 to 0.25 (P=0.53) at 6 months. The average number of all-cause hospitalisations before inclusion increased from 0.57 to 0.58 (P=0.50) at 6 months. There was no significant difference in average length of stay and time to re-admission. CONCLUSION: We did not highlight the impact of PRADO on the rate of re-hospitalisation of heart failure patients.

Antiviral RNA interference in mammalian cells.

In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.