Tracheostomies after SARS-CoV-2 intubation, performed by academic otorhinolaryngologists in the Paris area of France: Preliminary results.

OBJECTIVE: To analyse tracheostomies after intubation for SARS-Cov-2 infection performed by otorhinolaryngologists in 7 university hospitals in the Paris area of France during the month March 24 to April 23, 2020. MATERIAL AND METHODS: A multicentre retrospective observational study included 59 consecutive patients. The main goals were to evaluate the number, characteristics and practical conditions of tracheostomies, and the COVID-19 status of the otorhinolaryngologists. Secondary goals were to analyse tracheostomy time, decannulation rate, immediate postoperative complications and laryngotracheal axis status. RESULTS: Tracheostomy indications were for ventilatory weaning and extubation failure in 86% and 14% of cases, respectively. The technique was surgical, percutaneous or hybrid in 91.5%, 3.4% and 5.1% of cases, respectively. None of the operators developed symptoms consistent with COVID-19. Postoperative complications occurred in 15% of cases, with no significant difference between surgical and percutaneous/hybrid techniques (P=0.33), although no complications occurred after percutaneous or hybrid tracheostomies. No procedures or complications resulted in death. The decannulation rate was 74.5% with a mean tracheostomy time of 20±12 days. In 55% of the patients evaluated by flexible endoscopy after decannulation, a laryngeal abnormality was found. On univariate analysis, no clinical features had a significant influence on tracheostomy time, decannulation rate or occurrence of laryngeal lesions. CONCLUSION: The main findings of the present retrospective study were: absence of contamination of the surgeons, heterogeneity of practices between centres, a high rate of complications and laryngeal lesions whatever the technique, and the specificities of the patients.

Comparison of the environmental impacts of online and classical conferences: the case of LCE 2020 and perspectives regarding the planetary boundaries.

International conferences such as CIRP LCE usually imply that their attendees travel around the world to reach the venue. Several online conferences have already been organised, but the year 2020 was particular because of the COVID-19 pandemics which obliged to cancel or modify dramatically all the events planned from the second quarter of that year. The CIRP Life Cycle Engineering conference was no exception and all arrangements made before March were cancelled or modified in order to host the conference online. This article presents the environmental impact assessment of the online conference and its comparison to the estimation of the impacts if the event had taken place in Grenoble (France), as initially planned. This study confirms that an online conference has lower environmental impacts than a classical conference, except for freshwater quality. The main contributors are the country energy mix of the audience for the online conference and the travel by plane for the classical one. This article also shows that online conferences might contribute to stay within the planetary boundaries. These results encourages to improve the study of the environmental impacts of online conferences and to highlight the hotspots to be improved.

PD-L1 expression in the microenvironment and the response to checkpoint inhibitors in head and neck squamous cell carcinoma.

In head and neck squamous cell carcinoma (HNSCC), data from studies using checkpoint-inhibiting antibodies that target programmed death 1 (PD-1) or its ligand the programmed death ligand 1 (PD-L1) demonstrated outstanding clinical activity. Translational investigations also suggested some correlations between therapeutic response and PD-L1 expression in tumor tissue. We comprehensively summarize results that have evaluated PD-L1 expression in HNSCC. We discuss flaws and strength of current PD-1/PD-L1 detection, quantification methods and the evaluation of PD-L1 as a prognostic and theragnostic biomarker. Understanding tumor microenvironment may help understanding resistance to checkpoint inhibitors, designing clinical trials that can exploit drug combinations.

Impact of the first month of Covid-19 lockdown on oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments.

OBJECTIVE: To evaluate the impact of the first month of lockdown related to the Covid-19 epidemic on the oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments. MATERIAL AND METHODS: A multicenter prospective observational assessment was conducted in 6 university hospital otorhinolaryngology departments (Paris Centre, Nord, Est and Sorbonne) during the 1-month periods before (Month A) and after (Month B) lockdown on March 17, 2020. The main goal was to evaluate lockdown impact on oncologic surgical activity in the departments. Secondary goals were to report population characteristics, surgery conditions, postoperative course, progression of Covid status in patients and surgeons, and adverse events. RESULTS: 224 procedures were performed. There was 10.9% reduction in overall activity, without significant difference between departments. Squamous cell carcinoma and larynx, hypopharynx, oropharynx, oral cavity and nasal cavity and sinus locations were predominant, at 79% and 75.8% of cases respectively, with no significant differences between months. T3/4 and N2/3 tumors were more frequent in Month B (P=.002 and .0004). There was no significant difference between months regarding surgical approach, type of reconstruction, postoperative course, tracheotomy and nasogastric feeding-tube time, intensive care stay or hospital stay. None of the Month A patients were Covid-19-positive, versus 3 in Month B, without adverse events. None of the otorhinolaryngologists involved in the procedures developed symptoms suggesting Covid-19 infestation. CONCLUSION: The present study underscored the limited impact of the Covid-19 epidemic and lockdown on surgical diagnosis and cancer surgery in the Ile de France university otorhinolaryngology departments, maintaining chances for optimal survival without spreading the virus.

Sentinel lymph node biopsy in cutaneous head and neck melanoma.

PURPOSE: Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. METHODS: A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. RESULTS: One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). CONCLUSION: As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.

Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT (1A) receptor antagonist and potential novel antidepressant.

BACKGROUND AND PURPOSE: As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT(1A) receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT(1A) receptor antagonist activities, was evaluated in preclinical models. EXPERIMENTAL APPROACH: Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models. KEY RESULTS: WAY-211612 inhibited 5-HT reuptake (K(i) = 1.5 nmol.L(-1); K(B) = 17.7 nmol.L(-1)) and exhibited full 5-HT(1A) receptor antagonist activity (K(i) = 1.2 nmol.L(-1); K(B) = 6.3 nmol.L(-1); I(max) 100% in adenyl cyclase assays; K(B) = 19.8 nmol.L(-1); I(max) 100% in GTPgammaS). WAY-211612 (3 and 30 mg.kg(-1), po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT(1A) receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3-30 mg.kg(-1), po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg.kg(-1), s.c.) and a 5-HT(1A) antagonist (WAY-100635; 0.3 mg.kg(-1), s.c). WAY-211612 (3.3-30 mg.kg(-1), s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3-30 mg.kg(-1), i.p. and 10-56 mg.kg(-1), po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg.kg(-1), i.p.) in the rat scheduled-induced polydipsia model. CONCLUSIONS AND IMPLICATIONS: These findings suggest that WAY-211612 may represent a novel antidepressant.

A new colorimetric assay for studying and rapid screening of membrane penetration enhancers.

PURPOSE: This work aims to demonstrate a novel chemical assay for rapid screening and analysis of the mode of action of membrane interaction by penetration enhancers. METHODS: The new bio-mimetic membrane assembly, consisting of supramolecular aggregates of lipids and conjugated polydiacetylene, undergoes visible and quantifiable blue-red color transitions upon interaction with penetration enhancers. RESULTS: The new colorimetric model has been employed to examine various classes of penetration enhancers, including 1-dodecylhexahydro-2H-azepin-2-one (Azone), oleic acid, propylene-glycol, menthol, ethoxyglycol-diethyleneglycol-monoethyl-ether (Transcutol), polysorbate-polyethylenesorbitan-monolaurate (Tween-20), and the drug 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one (Diazepam). The assay enables to evaluate the validity of various observations and hypotheses proposed in previous studies regarding permeation enhancement activities. Our results suggest, for example. that propylene glycol (PG) by itself does not interfere with membranes, but rather exhibits synergistic effect in combination with other penetration enhancers. Similarly, our data demonstrate that Transcutol does not independently interact with membranes. The colorimetric system also indicates that interaction of penetration enhancers with membranes depend upon the lipid phase, as well as the self-assembly properties of the enhancer molecules. CONCLUSIONS: The new biomimetic model membrane system can be applied for rapid screening of the activities of penetration enhancers, and provides insight into the mechanisms of permeability of membrane-active compounds.

Studies towards the next generation of antidepressants. Part 1: Indolylcyclohexylamines as potent serotonin reuptake inhibitors.

A series of indolylcyclohexylamines possessing potent and selective serotonin reuptake inhibition is reported. The most interesting compounds proved to have subnanomolar 5-HT transporter activity, and exhibited moderate 5-HT(1A) affinity.

Potent, selective tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus.

A series of potent, selective 5HT2B receptor antagonists has been identified based upon yohimbine, with SAR studies resulting in a 1000-fold increase in 5HT2B receptor affinity relative to the starting structure (-log KBS > 10.0 have been obtained). These high-affinity tetrahydro-beta-carboline antagonists are able to discriminate among the 5HT2 family of serotonin receptors, with members of the series showing selectivities of more than 100-fold versus both the 5HT2A and 5HT2C receptors based upon radioligand binding and functional assays. As the first compounds reported with such selectivity and enhanced receptor affinity, these tetrahydro-beta-carboline antagonists are useful tools for elucidating the role of serotonin acting at the 5HT2B receptor in normal and disease physiology.

Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.

Epirubicin in previously untreated patients with small cell lung cancer: a phase II study by the EORTC Lung Cancer Cooperative Group.

Epirubicin 110 mg/m2 was administered intravenously every 3 weeks to 41 elderly and/or unfit, previously untreated patients with small cell lung cancer (SCLC). There were three complete responses, 16 partial responses and 14 treatment failures, with a response rate of 57% in 33 evaluable patients. The main toxicity was haematological, characterised by leukopenia and, less frequently, thrombocytopenia and anaemia. There were three toxic deaths due to infection occurring during leukopenia. Non-haematological side effects were alopecia, nausea, stomatitis and diarrhoea. WHO grade 2 cardiac toxicity was seen in 3 patients after a cumulative dose of more than 740 mg/m2. In conclusion epirubicin is an active agent in untreated SCLC.

[Climatologic parameters and myocardial infarction]. / Paramètres climatologiques et infarctus myocardique.

535 patients admitted to hospital with myocardium infarct which was confirmed in a determined period and within a 80 kilometers radius from a city of the East of France were compared to the meteorological parameters of the day when the infarct occurred and of the day preceding its occurrence. On one hand, climatic parameters were selected: atmospheric pressure, temperature of the air under shelter, relative humidity, wind speed and wind direction, hydrometeors and electrometeors; on the other hand, parameters of solar and planetary activity: daily flare index, AA index, Ap index or daily planetary index, phases of the moon. The analytic study concerning all acute vascular accidents (infarcts and cerebral accidents all together) enabled to us to notice a higher frequency of vascular accidents in various meteorological circumstances: atmospheric pressure lower than 990 mb, temperature lower than 12 degrees, wind of sector North to South-South West, hoar-frost with fog, rain, snow, first quarter of the moon, daily flare index lower than 530, magnetic activity lower than 6. A factorial analysis of correspondence enabled to us to understand the problem better and to determine "an infarct area" in which main meteorological factors appeared: low or decreasing atmospheric pressure, relative or increasing humidity, clear or increasing solar activity, steady magnetic activity; other factors could play an apparently less important role: low temperature, snow, decrease of wind speed, full moon, wind of sector East to North-East, South-South West. Consequently it appeared in that study that the occurrence of myocardium infarct corresponded to a climatic tendency corresponding to cold, bad or deteriorating weather.