Summary report of the Standards, Options and Recommendations for the management of patients with non-small-cell lung carcinoma (2000)

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Infection prevention for immunocompromised patients: a cross-translational multicentric survey of current organization in France

International audienceObjectivesTo evaluate current organization of infection prevention for immunocompromised patients (ICP) at a countrywide level.MethodsNationwide cross-sectional multicenter study based on an online survey disseminated in 2022 to physicians invested with preventive healthcare missions.ResultsA total of 341 physicians (96% graduates, 32% infectious disease specialists), participated in the survey, with a median age of 40 [35–51] years. On-site access to infection prevention consultations for ICP was reported by 30%, dedicated pre-travel consultations for ICPs by 29%, consultations for infection prevention in solid organ transplant candidates by 16% and return-to-work consultations for ICPs by 6%. Most participants (73%) were aware of nationwide vaccination guidelines for ICP, while 50% felt comfortable using them. Tools for infection prevention advice and ICP vaccination had been developed by 10%, while 89% would have appreciated access to tools developed by others.ConclusionsInfection prevention for ICPs remains neglected. Guidelines covering all fields of prevention for ICPs would be more than welcome

Experimental study of the stability and phase relations of clays at high temperature in a thermal gradient

International audienc

Microbiology and antibiotics after second-stage revision of periprosthetic joint infections: A two-year follow-up cohort

International audienceBackground: Optimal duration of antimicrobial regimen after reimplantation of two-stage procedures for periprosthetic joint infection (PJI) is poorly standardized. The aim of this study was to assess the characteristics of reimplantation microbiology with 6 weeks (2nd stage positive culture) or 10 days (2nd stage negative culture) of antibiotics in patients with complex chronic PJI and factors associated with microbiology at reimplantation. Patients and methods: We performed a retrospective single-center study including all consecutive complex PJI recipients managed by two-stage surgery in a referral centre, from 2015 to 2018. Outcome was assessed at a minimum 2-year follow-up. Logistic regression analysis was performed to assess predictors of reimplantation microbiology. Results: Fifty patients (median age 69 [62–77] years) were included. PJI predominantly involved the hip (48%). The most common microorganisms were Staphylococcus aureus (36%), and coagulase-negative staphylococci (24%). At the second stage, reimplantation microbiology was positive for 10 patients (20%). Documentation was obtained within 48 hours. With median follow-up of 41 [30–50] months after reimplantation, treatment failure occurred in 4 patients (8%). Using log-rank to compare Kaplan–Meier survival curves, no difference in the probability of treatment failure was found according to reimplantation microbiology (P = 0.34). After adjustment, relapse was not associated with positive reimplantation microbiology (P = 0.53). Conclusions: In this work, positive microbiology at reimplantation did not predict treatment failure. Rapid growth at post-reimplantation suggests that antibiotic use should not exceed 10 days when cultures are negative. Additional studies are needed to determine the optimal duration of antibiotic therapy in case of negative microbiology. © 2022 Elsevier Masson SA

Oxoazabenzo[de]anthracenes conjugated to Amino Acids: Synthesis and evaluation as DNA-binding antitumor agents.

We report the synthesis of an original series of oxoazabenzo[de]anthracenes conjugated to an amino acid: Ala, Phe, Pro, Lys, or Gly (4a-e, respectively). The compounds, derived from 1,8-dihydroxyanthracene-9,10-dione, were studied for DNA binding and cytotoxicity. Melting temperature, fluorescence quenching, and surface plasmon resonance methods all indicated that the lysine derivative 4d binds to DNA much more strongly that the Pro, Ala, and Gly conjugates whereas the Phe analogue showed the lowest DNA binding capacity. These compounds form intercalation complexes with DNA, as judged from electric linear dichroism and topoisomerase I-based DNA unwinding experiments. Preferential binding of 4d to defined sequences such as 5'-CTAAAGG and 5'-ATGC was evidenced by DNase I footprinting. This Lys conjugate was found to be over 20 times more cytotoxic to CEM human leukemia cells than the other conjugates, with an IC50 in the submicromolar range. A high antiproliferative activity, likely attributable to the enhanced DNA binding capacity, is maintained despite the incapacity of the compound to stabilize topoisomerase-DNA covalent complexes. The cell cycle effects of 4d consisted in an S phase accumulation of cells coupled with a pro-apoptotic action (appearance of hypodiploid sub-G1 cells) which were confirmed by measuring the inhibition of BrdU incorporation into DNA and labeling of phosphatidylserine residues with annexin V-FITC by means of flow cytometry. Altogether, the work provides interesting structure-activity relationships in the oxoazabenzo[de]anthracene-amino acid conjugate series and identifies the lysine derivative 4d as a promising candidate for further in vivo evaluation and drug design

DNA intercalation, topoisomerase II inhibition and cytotoxic activity of the plant alkaloid cryptolepine

Cryptolepine and neocryptolepine are two indoloquinoline alkaloids isolated from the roots of the African plant Cryptolepis sanguinolenta. Both drugs have revealed antibacterial and antiparasitic activities and are strongly cytotoxic to tumour cells. We have recently shown that cryptolepine can intercalate into DNA and stimulates DNA cleavage by human topoisomerase II. In this study, we have investigated the mechanism of action and cytotoxicity of neocryptolepine, which differs from the parent isomer only by the orientation of the indole unit with respect to the quinoline moiety. The biochemical and physicochemical results presented here indicate that neocryptolepine also intercalates into DNA, preferentially at GC-rich sequences, but exhibits a reduced affinity for DNA compared with cryptolepine. The two alkaloids interfere with the catalytic activity of human topoisomerase II but the poisoning activity is slightly more pronounced with cryptolepine than with its isomer. The data provide a molecular basis to account for the reduced cytotoxicity of neocryptolepine compared with the parent drug