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SEOM-TTCC clinical guideline in nasopharynx cancer (2021).
No full textNasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy (RT) is the cornerstone of locoregional treatment of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.S
High IGKC-Expressing Intratumoral Plasma Cells Predict Response to Immune Checkpoint Blockade.
No full textResistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy, which otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB, and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral Plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq-defined fraction. Finally, we generated a 15-gene prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and Plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes.The work is funded by the Instituto de Salud Carlos III through the projects PI18/01592 (to M.C.) and FI19-00112 (to A.L.-I.) (Co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”), Sistema Andaluz de Salud, through the projects SA 0263/2017, Nicolás Monardes (to I.B.) and PI-0121-2020, RH-0090-2020, Consejería de Salud (to I.B., J.O.), Spanish Group of Melanoma (Award for Best Research Project 2020) (to I.B.), Fundación Bancaria Unicaja through the project C19048 (to I.B., M.C.), Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology (to I.B., E.A.), Consejería de Salud PI-01212020 (to I.B., E.P.-R.), Melanoma Spanish Group, Consejería de Transformación Económica, Industria, Conocimiento y Ciencia CV20-62050 (to I.B.), and the China Scholarship Council (CSC) 201600160066 Grant (to Q.X.) and the Karolinska Institutet Fonder Grants (to Q.X.).S
Current Positioning against Severe Infections Due to Klebsiella pneumoniae in Hospitalized Adults.
No full textInfections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.S
Adipokines Profile and Inflammation Biomarkers in Prepubertal Population with Obesity and Healthy Metabolic State.
No full textBackground and aims: Obesity and high body max index (BMI) have been linked to elevated levels of inflammation serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and resistin. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of the fat cell and also systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers in a metabolically healthy prepubertal population with obesity (MHOPp) from Malaga (Andalusia, Spain). (2) Methods: 144 MHOPp subjects (aged 5-9 years) were included in this study as they met ≤1 of the following criteria: waist circumference and blood pressure ≥ 90 percentile, triglycerides > 90 mg/dL, high-density lipoprotein cholesterol (HDL-c) 90 mg/dL, high-density lipoprotein cholesterol (HDL-c)< 40 mg/dL, or impaired fasting glucose (≥100 md/dL). Selected subjects followed a personalized intensive lifestyle modification. Anthropometric measurements, inflammation biomarkers, and adipokine profile were analyzed after 12 and 24 months of intervention. Results: 144 MHOPp participants (75 boys—52% and 69 girls—48%; p = 0.62), with an age of 7.8 ± 1.4 years and a BMI of 24.6 ± 3.3 kg/m2, were included in the study. After 24 months of intervention with MedDiet and daily physical activity, a significant decrease in body weight (−0.5 ± 0.2 SD units; p < 0.0001) and BMI (−0.7 ± 0.2 SD units; p < 0.0001) was observed in the total population compared to baseline. Serum inflammatory biomarkers (IL-6, TNF-alpha, and CRP) were significantly reduced after 24 months of intervention. The adipokine profile (adiponectin and resistin) did not improve with the intervention, as adiponectin levels significantly decreased and resistin levels increased in the entire population. Inflammatory biomarkers and the adipokine profile had a significant correlation with anthropometric parameters, body composition, and physical activity. Conclusions: After 24 months of lifestyle modification, our MHOPp participants reduced their BMI Z-score, leading to an improvement in inflammatory biomarkers but causing deterioration in the adipokine profile, which does not improve with the MedDiet and physical activity intervention. Adequate family education about healthier habits is necessary to prevent and reduce excessive obesity increase in childhood.This work was supported by grants from the Instituto de Salud Carlos III, co-financed by the Fondo Europeo de Desarrollo Regional-FEDER (“Centros de Investigación En Red” (CIBER, CB06/03/0018)). M. Rosa Bernal-Lopez was supported by the “Miguel Servet Type II” program (CPII/00014) and the “Nicolas Monardes” program (C1-0005-2020), Lidia Cobos Palacios was supported by the “Rio Hortega” program (CM20/00125) from the ISCIII-Madrid (Spain), co-financed by the Fondo Europeo de Desarrollo Regional-FEDER. Monica Muñoz Ubeda was supported by the Consejería de Salud, Junta de Andalucía (RH-0100-2020).S
A step forward in antibiotic use and resistance monitoring: a quarterly surveillance system pilot in 11 European Union/European Economic Area countries, September 2017 to May 2020.
No full textBackgroundSurveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) in Europe is currently annual.AimTo study the feasibility and scalability of a quarterly AMR/AMU surveillance system in the European Union/European Economic Area (EU/EEA).MethodsWe conducted a longitudinal study within the scope of the EU-JAMRAI project. Seventeen partners from 11 EU/EEA countries prospectively collected 41 AMU and AMR indicators quarterly from September 2017 to May 2020 for the hospital sector (HS) and primary care (PC). Descriptive statistics and coefficients of variation (CV) analysis were performed.ResultsData from 8 million hospital stays and 45 million inhabitants per quarter were collected at national (n = 4), regional (n = 6) and local (n = 7) levels. Of all partners, five were able to provide data within 3 months after each preceding quarter, and eight within 3-6 months. A high variability in AMU was found between partners. Colistin was the antibiotic that showed the highest CV in HS (1.40; p S
Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD.
No full textNAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials. After a systematic review of NAFLD clinical trials to May 2021, applying strict selection criteria, the following primary outcomes were observed: (a) NASH resolution, with no worsening of fibrosis when available; (b) fibrosis improvement ≥ 1 stage, with no worsening of NAS when available; (c) worsening of NAS; (d) worsening of liver fibrosis ≥ 1 stage, including the progression to cirrhosis on histopathology. Other histological, clinical, and biochemical outcomes were considered secondary endpoints. Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Twenty-seven randomized clinical trials were included. The pooled efficacy for NASH resolution receiving experimental therapy was 19% (95%CI 15-23; I2 96.2%) compared with placebo 10% (95%CI 7-12; I2 85.8%) (OR 1.66 (95%CI 1.24-2.21); I2 57.8%), while it was 26% (95%CI 22-29); I2 90%)) versus 18% (95%CI 15-21; I2 59%)) for fibrosis improvement (OR 1.34 (95%CI 1.13-1.58); I2 25.4%). For these outcomes, the therapy showed higher efficacy in trials longer than 48 weeks, with This meta-analysis provides information about the efficacy of the therapy versus placebo by comparing different and combined trial outcomes such as NASH resolution, fibrosis improvement, and NAS and fibrosis worsening. Changes in the experimental design and selection criteria of the clinical trials might be suitable to increase the efficacy.S
Which one? A comparative study of traditional and sports uniforms on academic achievement, cognitive performance, playtime, bullying, and discrimination in adolescents: The Cogni-Action Project.
No full textThe aim of this study was to compare academic achievement, cognitive performance, playtime, bullying, and discrimination in adolescents according to traditional uniforms (TUs) and sports uniforms (SUs) worn at school, while simultaneously exploring the influence of the school vulnerability index. A total of 988 Chilean adolescents (52.6% boys) aged 10-14 years participated in this cross-sectional study. Academic achievement was evaluated by the average grade in maths, language, and science grades, while cognitive performance was assessed through eight cognitive tasks. TUs affecting physical activity, playtime, bullying, and discrimination were queried. Mixed model analyses were performed. No differences were observed in academic achievement (TU: 5.4 ± 0.1 vs. SU: 5.5 ± 0.2, p = 0.785) or in cognitive performance (TU: 99.6 ± 0.8 vs. SU: 98.9 ± 1.8, p= 0.754) according to the school uniformtype. Moreover, 64.1 % of participants declared that wearing TU affects their physical activity (traditional uniforms: + 8 min and sports uniforms: + 20 min), and those who believed so spent more time playing than those who answered negatively (14.5 min, p = 0.012). Finally, adolescents wearing SU displayed a lower feeling of bullying and discrimination; this finding depended mainly on the school's vulnerability. It is concluded that wearing TU does not show an educational advantage at an academic and cognitive level that justifies its obligation. In addition, it could be suggested that schools consider adolescents' opinions in adopting a more comfortable uniform, such as the SU. This feasible and low-cost measure would help to increase adolescents' physical activity during the school day, and, contrary to belief, it would not be related to increased feelings of bullying and discrimination
Fast-track protocols in laparoscopic liver surgery: Applicability and correlation with difficulty scoring systems.
No full textFew series have reported the utility of fast-track protocols (FTP) in minimally invasive liver surgery. To report the applicability of FTP in minimally invasive liver surgery and to correlate with difficulty scores. The series of patients undergoing minimally invasive liver surgery from 2014 was analyzed. Iwate, Southampton and Gayet's scores were compared as predictors of FTP adherence. Accomplishment of FTP was considered within 24-h, 48-h and 72-h. Multivariate models were performed to define discharge From 160 cases, 78 were candidates for FTP, of which 22 (28.2%), 19 (24.4%) and 14 (17.9%) were discharged in The development of aggressive FTP is feasible and < 24-h stay can be achieved even in moderate and advanced complexity cases. Difficulty scores, including body mass index value, may be useful to predict which cases may adhere to these protocols.S
Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study.
No full textChildren aged younger than 3 years were excluded from the ELIANA phase 2 trial of tisagenlecleucel in children with acute lymphoblastic leukaemia. The feasibility, safety, and activity of tisagenlecleucel have not been defined in this group, the majority of whom have high-risk (KMT2A-rearranged) infant acute lymphoblastic leukaemia and historically poor outcomes despite intensification of chemotherapy, and for whom novel therapies are urgently needed. We aimed to provide real-world outcome analysis of the feasibility, activity, and safety of tisagenlecleucel in younger children and infants with acute lymphoblastic leukaemia. We did an international, multicentre, retrospective cohort study at 15 hospitals across ten countries in Europe. Eligible patients were children aged younger than 3 years at screening between Sept 1, 2018, and Sept 1, 2021, who were screened for tisagenlecleucel therapy for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia according to licensed indications. Patients received a single intravenous infusion of tisagenlecleucel. We tracked chimeric antigen receptor T-cell therapy outcomes using a standardised data reporting form. Overall survival, event-free survival, stringent event-free survival, B-cell aplasia, and toxicity were assessed in all patients who received a tisagenlecleucel infusion. 38 eligible patients were screened, of whom 35 (92%) received a tisagenlecleucel infusion. 29 (76%) of 38 patients had KMT2A-rearranged acute lymphoblastic leukaemia, and 25 (66%) had relapsed after previous allogeneic haematopoietic stem-cell transplantation (HSCT). Patients had previously received a median of 2 lines (IQR 2-3) of (non-HSCT) therapy. Seven (18%) of 38 patients had received inotuzumab and 14 (37%) had received blinatumomab. After a median of 14 months (IQR 9-21) of follow-up, overall survival at 12 months after tisagenlecleucel infusion was 84% (64-93; five patients had died), event-free survival was 69% (47-83; nine events), and stringent event-free survival was 41% (23-58; 18 events). The probability of ongoing B-cell aplasia was 70% (95% CI 46-84; seven events) at 12 months. Adverse events included cytokine release syndrome, which occurred at any grade in 21 (60%) of 35 patients and at grade 3 or worse in five (14%), and neurotoxicity at any grade in nine (26%), none of which were severe. Measurable residual disease-negative complete response with or without haematological recovery occurred in 24 (86%) of 28 patients who had measurable disease. These data suggest that tisagenlecleucel has antitumour activity and has an acceptable safety profile for young children and infants with B-cell precursor acute lymphoblastic leukaemia.S