LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology

Objectives: The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non-small cell lung cancer (NSCLC) patients treated with first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods: Stage IV NSCLC patients with locally confirmed EGFR-TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first- or second-generation EGFR-TKI as first-line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression-free survival (PFS) event or until study completion (72-week follow-up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results: A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty-six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow-up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001). Conclusion: Detection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd

Ibero-American Consensus on Low- and No-Calorie Sweeteners : Safety, Nutritional Aspects and Benefits in Food and Beverages

International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2\u207b4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable

Association between source control and mortality in 258 patients with intra-abdominal candidiasis: a retrospective multi-centric analysis comparing intensive care versus surgical wards in Spain

Early empiric therapy and adequate resuscitation have been identified as main predictors of outcome in patients with candidemia or bacteremia. Moreover, source control is a major determinant in infectious sites when feasible, as a main technique to reduce microbiological burden. A retrospective, multicenter, cohort study was performed at surgical wards and intensive care units (ICU) of three University Hospitals in Spain between 2010 and 2014, with the aim of improving understanding of the interaction between source control, early antifungal therapy, and use of vasoactives in patients with intra-abdominal candidiasis (IAC). Source control was defined as all physical actions taken to control a focus of infection and reduce the favorable conditions that promote microorganism growth or that maintain the impairment of host defenses. Two hundred and fifty-eight patients with IAC were identified. Sixty-one patients were at ICU for diagnosis. Mortality was higher in the ICU group compared to what was documented for the non-ICU group (35 % vs 19.5 %, p = 0011). Adequate source control within 48 h of diagnosis was achieved in 60 % of the cohort. In multivariate analysis, inadequate source control was identified as the only common risk factor for 30-day mortality in both groups (ICU group OR: 13.78 (95% CI: 2.60\u201372.9, p = 0.002) and non-ICU group OR: 6.53 (95% CI: 2.56\u201316.61, p = <0.001). The population receiving both adequate source control and adequate antifungal treatment was the one associated with a higher survival rate, in both the ICU and surgical groups. Source control remains a key element in IAC, inside and outside the intensive care unit. Early antifungal treatment among ICU patients was associated with lower mortality

Symptom severity and quality of life in the management of vulvovaginal atrophy in postmenopausal women

Objectives: To evaluate the association between treatments for vulvovaginal atrophy (VVA) and symptom frequency and severity, quality of life (QoL) and sexual functioning in postmenopausal women. Study design: Cross-sectional survey conducted in postmenopausal women aged 45\u201375 years. Data on demographic and clinical variables, as well as vaginal, vulvar and urinary symptoms were collected. The EuroQoL questionnaire (EQ5D3L), the Day-to-Day Impact of Vaginal Aging (DIVA), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale - revised (FSDS-R) were filled out. Main outcome measures: Association between treatments for VVA and symptom frequency. Results: Women on VVA treatment presented with more severe symptoms. The sexual function score was higher in the treated women (FSFI: 15.6 vs 16.7; p=0.010), as was the score for sexual distress (FSDS-R: 9.2 vs 12.3, p &lt; 0.0005). The systemic hormone group presented with fewer VVA symptoms, lower vaginal impact (DIVA), and better sexual function (FSFI and FSDS-R) and vaginal health. The rates of sexual distress and vulvar atrophy were higher in the non-hormonal treatment group. No significant differences were found according to treatment duration. Conclusions: Postmenopausal women with VVA receiving treatment complained of more severe symptoms than those untreated. Women on systemic treatment had fewer and milder VVA symptoms and presented with better vaginal and vulvar health than women on other treatments. Many women request effective local treatment too late, when VVA symptoms are already severe. Our data suggest that VVA treatments should ideally be initiated when symptoms commence and cause distress, rather tha

The burden of vulvovaginal atrophy on women's daily living: Implications on quality of life from a face-to-face real-life survey

Objective:This subanalysis of the European Vulvovaginal Epidemiology Survey study aimed to assess the correlation of vulvovaginal atrophy (VVA) symptoms and severity, when confirmed by objective gynecologic examination, with the quality of life of postmenopausal women.Methods:Women aged 45 to 75 years with confirmation of last menstrual period more than 12 months before, who attended menopause or gynecology centers, were included. Those women had at least one VVA symptom filled in a group of questionnaires, including EuroQol-EQ-5D-3L and Day-to-Day Impact of Vaginal Aging (DIVA). To confirm the VVA diagnosis, an objective gynecologic examination was also performed.Results:Of a total of 2,160 evaluable women, 66.3%, 30.5%, and 11.2% suffered from severe vaginal, vulvar, and urinary symptoms, respectively. VVA was confirmed in more than 90% of the participants. Mean (\ub1SD) EQ-5D-3L score was 0.892\u200a\ub1\u200a0.144 and mean (\ub1SD) score on the associated visual analog scale was 71.7\u200a\ub1\u200a16.0. Mean (\ub1SD) DIVA score was 0.922\u200a\ub1\u200a0.653. For both EQ-5D-3L and DIVA, the overall scores and most of the dimensions/components were statistically significantly worse for women with severe VVA symptoms (vulvar and urinary) compared with women not affected by severe symptoms. Quality of life questionnaires showed worse scores in women where the diagnosis of VVA was confirmed by gynecologic examination.Conclusions:Severe VVA symptoms showed a direct association with worse quality of life in postmenopausal women. This important effect on the quality of life of many women should be recognized as equivalent to those from other conditions and pathologies of which there is greater awareness