Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Le cochon, un mythe sur le gril

Le cochon, un mythe sur le gri

CD5 expression in Merkel cell carcinoma and extracutaneous neuroendocrine carcinomas

International audienc

EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors?

The ADAURA trial has been significant for the perception of EGFR tyrosine kinase inhibitors (TKIs) as a tool for early stage non-small-cell lung cancer (NSCLC). It produced such great insight that the main TKI, Osimertinib, was rapidly integrated into international guidelines for adjuvant use. However, EGFR-mutant NSCLC is a complex entity and has various targeting drugs, and the benefits for patients might not be as clear as they seem. We reviewed trials and meta-analyses considering TKI adjuvant and neoadjuvant use. We also explored the influence of mutation variability and financial evaluations. We found that TKIs often show disease-free survival (DFS) benefits, yet studies have struggled to improve the overall survival (OS); however, the results from the literature might be confusing because of variability in the stages and mutations. The safety profiles and adverse events are acceptable, but costs remain high and accessibility might not be optimal. TKIs are promising drugs that could allow for tailored treatment designs

Women's perceptions and experience of adjuvant tamoxifen therapy account for their adherence: breast cancer patients' point of view

International audienceObjective: The aim of this study on primary breast cancer patients undergoing adjuvant tamoxifen treatment was to determine how their perceptions of the treatment and their experience of side-effects contributed to their adherence to the treatment. Methods: A consecutive series of primary breast cancer patients eligible for tamoxifen therapy were studied qualitatively by conducting semi-structured in-depth interviews at two French cancer centres. Results: The women aged 35-65 (N 5 34) were struggling with several issues involving their understanding and experience of the treatment, which have not been documented so far. These issues included confusion about the 'hormonal' nature and activity of tamoxifen and the etiology of the changes in their menopausal status, as well as the symbolic associations formed by patients about the paradox of taking a treatment that has aging effects but saves lives. Conclusions: This study shows the great physical burden often associated with tamoxifen treatment and brings to light women's own complex representations of the treatment and their interpretation of the side-effects. Better communication between health-care providers and patients should ultimately help to prevent refusal or discontinuation of tamoxifen treatment

IDH mutation status in a series of 88 head and neck chondrosarcomas: different profile between tumors of the skull base and tumors involving the facial skeleton and the laryngotracheal tract

International audienc

Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis

International audienceAll tumors have in common to reactivate a telomere maintenance mechanism to allow for unlimited proliferation. On the other hand, genetic instability found in some tumors can result from the loss of telomeres. Here, we measured telomere length in colorectal cancers (CRCs) using TRF (Telomere Restriction Fragment) analysis. Telomeric DNA content was also quantified as the ratio of total telomeric (TTAGGG) sequences over that of the invariable Alu sequences. In most of the 125 CRCs analyzed, there was a significant diminution in telomere length compared with that in control healthy tissue. Only 34 tumors exhibited no telomere erosion and, in some cases, a slight telomere lengthening. Telomere length did not correlate with age, gender, tumor stage, tumor localization or stage of tumor differentiation. In addition, while telomere length did not correlate with the presence of a mutation in BRAF (V-raf murine sarcoma viral oncogene homolog B), PIK3CA (phosphatidylinositol 3-kinase catalytic subunit), or MSI status, it was significantly associated with the occurrence of a mutation in KRAS. Interestingly, we found that the shorter the telomeres in healthy tissue of a patient, the larger an increase in telomere length in the tumor. Our study points to the existence of two types of CRCs based on telomere length and reveals that telomere length in healthy tissue might influence telomere maintenance mechanisms in the tumor

Chasteberry (Vitex agnus castus) as an alternative to synthetic progestogens? Composition of the fruits and effects on male and female pigs.

Synthetic progestogens are widely used in pig farms, but they may contaminate the environment. We evaluated if chasteberry (Vitex agnus castus), a shrub from Mediterranean areas, could be a natural substitute to synthetic hormones for gilts and could reduce boars' sexual behaviour. Our objective was to analyse 1) the composition of chasteberry fruits, 2) their effect on boars' sexual behaviour and plasma testosterone concentration, 3) their effect on gilts cyclicity synchronisation and plasma progestogens concentration. We showed that fruits contain flavonoids (34µg/g kaempferol, 88µg/g apigenin) using HPLC, phytosterols (5µg/g cholesterol, 31µg/g campesterol, 500µg/g beta-sitosterol, 79µg/g stigmasterol) and steroids (6ng/g pregnenolone, 3ng/g progesterone, 3ng/g 5alpha-dihydroprogesterone, 208ng/g 3alpha-dihydroprogesterone) using GC-MS/MS. Two replicates were conducted with 2 groups of 24 boars fed with 10 g vs 0 g per day of chasteberry fruit powder for 1 to 2 months, starting at 115 to 124 days of age. Plasma testosterone concentrations were lower (P < 0.05; permutation test) in chasteberry (2.27 +/-0.3 ng/ml) compared to control group (3.55 +/-0.59 ng/ml). The number of mounting behaviours in the first replicate was lower in chasteberry group (permutation test). Gilts were fed with 300 g twice a day of chasteberry fruit powder (n = 12) or 0 g (n = 6) or synthetic progestogens (n = 6) for 7 days. Plasma concentrations of progesterone were not different between groups. Analysis of inter-oestrus interval is in progress. In conclusion, we showed that 1) chasteberry fruits contain compounds with progestogen effect, 2) its consumption decreased boar libido in one replicate and plasma testosterone, 3) effects on gilts are under study

Lived experience and perceived advantages of therapeutic De-escalation: A qualitative study of older patients with breast cancer

One option for therapeutic de-escalation in older women with early breast cancer (EBC) is partial breast irradiation (PBI) instead of whole-breast irradiation (WBI) when the latter has no clear advantages. We aimed to explore the decision-making processes and the lived experiences of WBI and PBI from the perspectives of older women with EBC. Materials and methods: Thematic content analysis was performed on qualitative data collected using narrative interviews. Results: Twenty-two women aged 65 and over participated (ten patients who underwent WBI and twelve who underwent PBI). We identified three themes from their narratives: 1) Acceptance of a paternalistic relationship with physicians, 2) Strong need for an informed choice, and 3) PBI can help people conceal cancer-related physical marks. Narratives underlined participants' preferences for each of the two treatments and their perceptions about therapeutic de-escalation. Misconceptions about therapeutic de-escalation were observed. Discussion: When providing information about EBC treatment options, patients' perceived burden of side effects should be considered. Moreover, eliciting the value older patients place on available breast cancer treatments, as well as their related goals and preferences, could foster their participation in the therapeutic de-escalation decision-making process