Genetic inactivation of acetylcholinesterase causes functional and structural impairment of mouse soleus muscles

International audienceAcetylcholinesterase (AChE) plays an essential role in neuromuscular transmission. Not surprisingly, neuromuscular transmission during repetitive nerve stimulation is severely depressed in the AChE knockout mouse (KO). However, whether this deficit in AChE leads to skeletal muscle changes is not known. We have studied the in vitro contractile properties of the postural and locomotor soleus muscles of adult KO and normal (wildtype, WT) mice, and this was completed by histological and biochemical analyses. Our results show that muscle weight, crosssectional area of muscle fibres and absolute maximal isometric force are all reduced in KO mice compared with WT mice. Of interest, the relative amount of slow myosin heavy chain (MHC-1) in muscle homogenates and the percentage of muscle fibres expressing MHC-1 are decreased in the KO mice. Surprisingly, AChE ablation does not modify twitch kinetics, absolute maximal power, fatigue resistance or citrate synthase activity, despite the reduced number of slow muscle fibres. Thus, a deficit in AChE leads to alterations in the structure and function of muscles but these changes are not simply related to the reduced body weight of KO mice. Our results also suggest that this murine model of congenital myasthenic syndrome with endplate AChE deficiency combines alterations in both neurotransmission and intrinsic muscle properties

High Frequency Characterization and Compact Electrical Modelling of Graphene Field Effect Transistors

International audienceThis paper deals with both DC and high frequency characterization of graphene devices, associated to compact electrical modelling. Pulsed I-V and microwave characterization of several Graphene Field-Effect Transistor (GFET) generations fabricated on SiC substrates were investigated in order to derive a first approach for non-linear device modelling. As illustrated here with a Graphene Nano Ribbon FET (GNR FET), a compact electrical model was presented accounting the DC and HF characteristics in broad range of operating conditions. The differences between DC and pulsed I-V characterizations of the GNR FET are investigated and compared to simulations. The small signal behavior and some figure of merits (FOM) like current gain cut-off frequency ft maximum oscillation frequency fmax. The nonlinear modelling of GNR FET is becoming of prime importance along with technological efforts to demonstrate the actual potential of this promising technology. This approach was also applied to conventional GFET, with a large flake of graphene used as a device channel

Experiences of Inter-Hospital Transfers (IHT) by Patients and Relatives during the COVID-19 Pandemic in France: A Qualitative Study

International audienceBackground: The first wave of the COVID-19 epidemic led to a rapid and unexpected saturation of the French ICU, forcing the health care system to adapt. Among other emergency measures, inter-hospital transfers were carried out. Objective: To assess the psychological experience of patients and their relatives regarding inter-hospital transfers. Methods: Semi-structured interviews were conducted with transferred patients and their relatives. A phenomenological study design was used to examine subjective experiences and their meanings for the participants. Results: The analysis found nine axes pertaining to the experiences of IHT (inter-hospital transfers), grouped in three super-ordinate themes: Information about inter-hospital transfers, differences in patients’ and relatives’ experiences, and host hospital experience. It appears that patients felt little impacted by the transfers, unlike relatives who experienced intense anxiety when the transfer was announced. Good communications between patients and their relatives resulted in a good level of satisfaction regarding their host hospitals. COVID-19 and its somatic consequences seem to have had more psychological impact on the participants than the transfers by themselves. Conclusion: Our results suggest that there are limited current psychological consequences of the IHT implemented during the first wave of COVID-19, although the involvement of patients and their relatives in the organization of the IHT at the time of transfer could further limit them

Characteristics of never smoker lung cancer including environmental and occupational risk factors.

International audienceINTRODUCTION: Clinical characteristics and risk factors of nonsmoker patients with lung cancer are still debated. AIM AND METHODS: The aim of this work is to describe the characteristics of never smoker patients with lung cancer, focusing on occupational and environmental exposures, Data collected were: age, gender, histological types, methods of diagnosis, TNM staging, smoking, and occupational data. Statistical analysis included descriptive analyses, Pearson's chi-square or nonparametric tests, and logistic regressions. RESULTS: All lung cancers diagnosed between January 1, 1997 and December 31, 2006, representing 1493 cases were included. Lung adenocarcinoma (ADC) [Odds Ratio (OR)=2.5 (1.5-4.3), p<0.0001] as well as clinical stage I cases at diagnosis [OR=2.4 (1.3-4.3)] were most frequent in nonsmokers relative to ever smokers. Comparison of clinical features among male and female nonsmoker patients did not reveal significant differences. Conversely, strong differences appeared when comparing environmental tobacco smoke (ETS) and occupational exposures in nonsmoker women vs men: ETS exposure (78.6% nonsmoker women vs 21.4% nonsmoker men, p<0.0001), occupational exposure (9.4% vs 48.6%, p<0.0005). Noteworthy, a sizeable number of nonsmoker male (40.0%), and nonsmoker female (31.2%) patients had no known exposure to major lung carcinogens. CONCLUSIONS: Main risk factors (ETS and occupational exposure) may only explain some cases

Relationships between lung adenocarcinoma and gender, age, smoking and occupational risk factors: A case-case study.

International audienceBACKGROUND: The hypothesis that some risk factors for lung cancer may have more specific associations with particular histologic types remains controversial. The aim of this study was to investigate possible associations between adenocarcinoma and gender, age, smoking characteristics and selected occupational carcinogens in relation to other histologic types. METHODS: This study included all histologically confirmed lung cancer cases diagnosed consecutively in two French University hospitals from 1997 to 2006. All medical data were obtained by face-to-face patient interviews. Occupational carcinogen exposures of each patient were assessed by an industrial hygienist. Relationships between risk factors and adenocarcinoma were analyzed by case-case comparisons using unconditional logistic regressions (ULRs). RESULTS: A total of 1493 subjects were enrolled in this study, comprising 1303 men (87.3%), 67 nonsmokers (4.5%) and 489 adenocarcinomas (32.7%). Using ULR, no associations were observed between adenocarcinoma and age, gender or smoking characteristics except for a negative relationship with smoking duration (p<0.0001). Significant associations were observed between ADC and exposure to welding fumes and silica in the whole population and with polycyclic aromatic hydrocarbons in ever smokers. CONCLUSION: This study demonstrated that some risk factors, such as duration of smoking and certain occupational exposures but not gender or age, have a more important influence on the incidence of lung ADC than on other histologic types. As the distribution of histologic types may reflect underlying biological mechanisms, these findings also suggest that lung carcinogenesis pathways should be studied in relation to smoking duration and other lung cancer risk factors

French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas

International audienceAnaplastic lymphoma kinase (ALK) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib. Although fluorescence in situ hybridisation (FISH) is the reference diagnostic technique, immunohistochemistry (IHC) could be useful for pre-screening.Diagnostic yields of ALK IHC, FISH and quantitative reverse transcriptase PCR performed in 14 French pathology/molecular genetics platforms were compared. 547 lung adenocarcinoma specimens were analysed using 5A4 and D5F3 antibodies, two break-apart FISH probes and TaqMan kits. Clinicopathological data were recorded.140 tumours were ALK rearranged (FISH with >= 15% of rearranged cells) and 400 were ALK FISH negative (= 15%, including six cases with FISH between 15% and 20%; eight were IHC positive with FISH between 10% and 14%. Sensitivity and specificity for 5A4 and D5F3 were 87% and 92%, and 89% and 76%, respectively. False-negative IHC, observed in 2.4% of cases, dropped to 1.3% for FISH >20%. Variants were undetected in 36% of ALK tumours.Discordances predominated with FISH ranging from 10% to 20% of rearranged cells and were centre dependent. IHC remains a reliable pre-screening method for ALK rearrangement detection

Tests immunohistochimiques PD-L1 dans les cancers du poumon non à petites cellules : recommandations par le groupe PATTERN de pathologistes thoraciques

International audienceLung cancer is the leading cause of cancer death in France with low response rates to conventional chemotherapy. Nevertheless, new therapies have emerged recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab (OPDIVO®, Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA®, Merck & Co), or PD-L1 ICI, such as atezolizumab (TECENTRIQ®, Genentech), durvalumab (IMFINZI®, Astra-Zeneca), and avelumab (BAVENCIO®, EMD Serono). The prescription of pembrolizumab for advanced stage non-small cell lung carcinoma (NSCLC) patients requires the demonstration of PD-L1 expression by tumor cells by immunohistochemistry (IHC) (minimum of 50% of positive tumor cells is required for first-line setting, and of 1% for second-line and beyond) and PD-L1 assay is now considered as a companion diagnostic tool for this drug. Numerous standardized PD-L1 assays performed on dedicated platforms have been validated in clinical trials, each antibody being associated to one specific PD1 or PD-L1 inhibitor. However, not all pathologists have access to the dedicated platforms and the high cost of these assays is still a limitation to their implementation; in addition, the small size of the NSCLC tumor samples does not allow to perform at the same time multiple assays for multiple drugs. The use of laboratory-developed tests seems feasible but their validation must guarantee the same sensitivities and specificities as standardized tests. In this context, the French group of thoracic pathologists PATTERN has teamed up with thoracic oncologists to provide recommendations on the indication, the critical technical steps and the interpretation of the PD-L1 IHC test to help pathologists to implement quickly and in the best conditions this new theranostic test

BMJ

To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. Multicentre, randomised, double blind, placebo controlled trial. 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. 926 adults scheduled for elective colorectal surgery. Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%). Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. ClinicalTrials.gov NCT02618720

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial

International audienceObjective To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery.Design: Multicentre, randomised, double blind, placebo controlled trial.Setting: 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019.Participants: 926 adults scheduled for elective colorectal surgery.Intervention: Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision.Main outcome measures: The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery.Results Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference −8.6%, 95% confidence interval −13.5% to −3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference −3.2%, 95% confidence interval −6.4% to −0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference −3.4%, −6.7% to −0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference −4.5%, −8.6% to −0.5%).Conclusion: Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. Trial registration ClinicalTrials.gov NCT02618720