Gold(I)-N-Heterocyclic Carbene Synthons in Organometallic Synthesis

The prominent role of gold-N-heterocyclic carbene (NHC) complexes in numerous research areas such as homogeneous (photo)catalysis, medicinal chemistry and materials science has prompted organometallic chemists to design gold-based synthons that permit access to target complexes through simple synthetic steps under mild conditions. In this review, the main gold-NHC synthons employed in organometallic synthesis are discussed. Mechanistic aspects involved in their synthesis and reactivity as well as applications of gold-NHC synthons as efficient pre-catalysts, antitumor agents and/or photo-emissive materials are presented

Synthesis and anticancer activity of Pt(0)-olefin complexes bearing 1,3,5-triaza-7-phosphaadamantane and N-heterocyclic carbene ligands

A series of Pt(0)-η2-olefin complexes bearing 1,3,5-triaza-7-phosphaadamantane (PTA) or N-heterocyclic carbenes are prepared following different synthetic strategies depending on the nature of coordinated alkene and spectator ligands. These new platinum(0) derivatives have been tested in vitro as anticancer agents toward three different tumor (human ovarian cancer A2780 and A2780cis and K562 myelogenous leukemia) and one non-tumor (Hacat keratinocytes) cell lines, proving to be in several cases highly and selectively cytotoxic against ovarian cancer cells. Furthermore, this antiproliferative effect is associated with the activation of an apoptosis process. In particular, complexes equipped with PTA as spectator ligand give comparable IC50 values on A2780 (cisplatin sensitive) and A2780cis (cisplatin resistant) cell lines, indirectly proving that these new Pt(0) substrates act with a mechanism of action conceivably different from cisplatin. This hypothesis is also confirmed by the fact that our compounds, in contrast to cisplatin, are not able to promote erythroid-differentiation activity on the K562 myelogenous leukemia cell line

Guillain-Barré syndrome in temporal association with influenza A vaccine

OBJECTIVE: To report a case of Guillain-Barré syndrome following influenza A (H1N1) 2009 vaccine. CASE DESCRIPTION: A four-year-old boy presented right thigh pain and ascending muscular weakness 15 days after the second dose of influenza A (H1N1) 2009 vaccine. The neurological examination revealed tetraparesis and areflexia. Electroneuromyography showed lower velocity and conduction blockage with small secondary axonal loss. Treated with intravenous immunoglobulin, the patient reached a plateau in the 4th day, followed by progressive muscular strength improvement. COMMENTS: The employment of large-scale influenza A (H1N1) 2009 vaccination and the preliminary reports from the American Surveillance Program suggest a significant association between Guillain-Barré syndrome and influenza A H1N1 2009 vaccination. All suspected cases of this association should be published for further evaluation. Vaccination remains the most effective method to prevent serious illness and death related to influenza.OBJETIVO: Descrever um caso de síndrome de Guillain-Barré em associação temporal com a vacina influenza A (H1N1) 2009. DESCRIÇAO DO CASO: Menino de quatro anos com queixa inicial de dor em coxa direita e perda de força muscular ascendente 15 dias após a segunda dose da vacina influenza A (H1N1) 2009. Ao exame neurológico apresentava tetraparesia e arreflexia, com predomínio em membros inferiores. A eletroneuromiografia evidenciou redução da velocidade e bloqueio de condução neuronal, com discreta perda axonal secundária. Foi tratado com imunoglobulina por via intravenosa, atingiu platô no quarto dia de evolução da doença e, depois, houve melhora progressiva da força muscular. COMENTÁRIOS: Com o emprego em larga escala da vacina influenza A (H1N1) 2009 em nosso meio e os dados preliminares do sistema de vigilância norte-americano mostrando associação temporal significante com a síndrome de Guillain-Barré, recomenda-se a descrição dos casos suspeitos dessa associação. A vacina continua sendo o método mais efetivo para prevenir doença grave e morte por influenza.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Strong altitudinal partitioning in the distributions of ectomycorrhizal fungi along a short (300 m) elevation gradient

• Changes in species richness and distributions of ectomycorrhizal (ECM) fungal communities along altitudinal gradients have been attributed to changes in both host distributions and abiotic variables. However, few studies have considered altitudinal relationships of ECM fungi associated with a single host to identify the role of abiotic drivers. To address this, ECM fungal communities associated with one host were assessed along five altitudinal transects in Scotland. • Roots of Scots pine (Pinus sylvestris) were collected from sites between 300 and 550–600 m altitude, and ECM fungal communities were identified by 454 pyrosequencing of the fungal internal transcribed spacer (ITS) region. Soil moisture, temperature, pH, carbon : nitrogen (C : N) ratio and organic matter content were measured as potential predictors of fungal species richness and community composition. • Altitude did not affect species richness of ECM fungal communities, but strongly influenced fungal community composition. Shifts in community composition along the altitudinal gradient were most clearly related to changes in soil moisture and temperature. • Our results show that a 300 m altitudinal gradient produced distinct shifts in ECM fungal communities associated with a single host, and that this pattern was strongly related to climatic variables. This finding suggests significant climatic niche partitioning among ECM fungal species

Real-world data on treatment outcomes in EGFR-mutant non-small-cell lung cancer patients receiving osimertinib in second or further lines

Aims: This study describes real-world outcomes of pretreated EGFR T790M-positive (T790M+) advanced non-small-cell lung cancer patients progressing after first- or second-generation tyrosine kinase inhibitors and receiving osimertinib, compared with T790M-negative (T790M-) patients. We have also described progression patterns and treatment sequences. Patients & methods: This is a retrospective multicenter Italian observational study including consecutive Caucasian patients referred between 2014 and 2018. Results: 167 patients were included. Median progression-free survival was 9.8 months (95% CI: 8.3-13.3) for T790M+ and 6.0 months (95% CI: 4.9-7.2) for T790M- patients, respectively. Median overall survival was 20.7 months (95% CI: 18.9-28.4) for T790M+ and 10.6 months (95% CI: 8.6-23.6) for T790M- patients, respectively. The T790M mutation correlated with absence of new sites of disease. After progression, most T790M+ patients continued osimertinib, whereas most T790M- patients received a different treatment line. Conclusion: Better outcomes were shown in patients receiving osimertinib. A more limited progression pattern for T790M+ was suggested

CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse—< 12 months from diagnosis—was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 109/L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible