Antibiotic Cycling Affects Resistance Evolution Independently of Collateral Sensitivity.

Antibiotic cycling has been proposed as a promising approach to slow down resistance evolution against currently employed antibiotics. It remains unclear, however, to which extent the decreased resistance evolution is the result of collateral sensitivity, an evolutionary trade-off where resistance to one antibiotic enhances the sensitivity to the second, or due to additional effects of the evolved genetic background, in which mutations accumulated during treatment with a first antibiotic alter the emergence and spread of resistance against a second antibiotic via other mechanisms. Also, the influence of antibiotic exposure patterns on the outcome of drug cycling is unknown. Here, we systematically assessed the effects of the evolved genetic background by focusing on the first switch between two antibiotics against Salmonella Typhimurium, with cefotaxime fixed as the first and a broad variety of other drugs as the second antibiotic. By normalizing the antibiotic concentrations to eliminate the effects of collateral sensitivity, we demonstrated a clear contribution of the evolved genetic background beyond collateral sensitivity, which either enhanced or reduced the adaptive potential depending on the specific drug combination. We further demonstrated that the gradient strength with which cefotaxime was applied affected both cefotaxime resistance evolution and adaptation to second antibiotics, an effect that was associated with higher levels of clonal interference and reduced cost of resistance in populations evolved under weaker cefotaxime gradients. Overall, our work highlights that drug cycling can affect resistance evolution independently of collateral sensitivity, in a manner that is contingent on the antibiotic exposure pattern.

Ultrasound measurement of optic nerve sheath diameter in a healthy adult Colombian population.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) provides a rapid, safe, and easy method for detecting increased intracranial pressure (ICP). However, the normal mean and upper limit values may vary according to sex, age, ethnicity, and ultrasound technique. AIM: We aimed to obtain the mean ONSD in a healthy Colombian adult population and to correlate it with demographic and anthropometric measures. METHODS: In a prospective study using a 10-13 MHz linear ultrasound probe, eye transverse diameter (ETD) and ONSD in the transverse (ONSD-TP) and sagittal planes (ONSD-SP) were measured in healthy adult volunteers in Bogota, Colombia. RESULTS: A total of 100 healthy subjects were included, with a mean age of 26,7 ± 8,3 years and 62 women. The mean ETD, ONSD-TP and ONSD-SP was 23.11 mm (95% confidence interval (CI): 22.90 mm-23.32 mm), 3.96 mm (95% CI: 3.85 mm-4.07 mm) and 4.0 mm (95% CI: 3.90 mm-4.11 mm), respectively. The ONSD in both planes ranged from 2.35 mm to 5.20 mm. There was a significant correlation between ONSD-SP and ONSD-TP (p < 0.0001) but no correlation between the ocular measures and demographic or anthropometric variables (p > 0.05). The intraclass correlation between the eyes was statistically significant. CONCLUSION: Our study shows that ultrasound-measured ONSD in healthy adults in Colombia is similar to that found worldwide. An ONSD of 5.5 mm may be considered the upper limit for healthy adults in Colombia. ONSD can be measured in either plane; there is a good correlation between the two eyes; and ONSD is not modified by demographic or anthropometric characteristics.

Social isolation after acquired brain injury: Exploring the relationship between network size, functional support, loneliness and mental health.

Social isolation can be a consequence of acquired brain injury (ABI). Few studies have examined the relationship between social isolation and mental health after ABI. In this cross-sectional and case-control study, we compared 51 ABI survivors and 51 matched healthy controls on measures of social isolation (network size, social support and loneliness) mental health and mental health problems. We explored the relationship between structural, functional and subjective components of social isolation and examined whether they were associated with mental health outcomes. No group differences were found on size of the network and perceived social support. The ABI group exhibited marginally higher levels of loneliness. The ABI group presented higher levels of depression, lower levels of quality of life and emotional wellbeing. In both groups, perception of social support was inversely related to subjective experience of loneliness. The relationship between network size and loneliness was only significant in the ABI group. Only loneliness significantly predicted quality of life, emotional wellbeing, depression and anxiety in people with brain injury. The relationship between social isolation variables in ABI is discussed, as well as the theoretical and clinical implications of focusing on loneliness to improve mental health after brain injury.

IAMBEE: a web-service for the identification of adaptive pathways from parallel evolved clonal populations.

IAMBEE is a web server designed for the Identification of Adaptive Mutations in Bacterial Evolution Experiments (IAMBEE). Input data consist of genotype information obtained from independently evolved clonal populations or strains that show the same adapted behavior (phenotype). To distinguish adaptive from passenger mutations, IAMBEE searches for neighborhoods in an organism-specific interaction network that are recurrently mutated in the adapted populations. This search for recurrently mutated network neighborhoods, as proxies for pathways is driven by additional information on the functional impact of the observed genetic changes and their dynamics during adaptive evolution. In addition, the search explicitly accounts for the differences in mutation rate between the independently evolved populations. Using this approach, IAMBEE allows exploiting parallel evolution to identify adaptive pathways. The web-server is freely available at http://bioinformatics.intec.ugent.be/iambee/ with no login requirement.

[Coaching for the treatment of obesity and overweight: a systematic review]. / Coaching para el tratamiento de la obesidad y sobrepeso: una revisión sistemática.

Coaching is increasingly used to treat obesity or overweight. We conducted a systematic review to explore the intervention's characteristics, effectivity, and quality of the published studies. The search was carried out on Pubmed, Scielo and Scopus databases. We considered studies published in peer-reviewed journals between 2014 and 2019 in English and Spanish. Following PRISMA guidelines, we selected and analyzed 22 articles, 46% of which were randomized controlled trials. Most of the studies had moderate quality, according to the risk of bias assessment carried out by three independent researchers based on the Study Quality Assessment Tool. Seventy seven percent of interventions targeted adults, and their duration ranged between two and 19 months. They were delivered in both private and public contexts, with face-to-face or remote interventions and combined techniques, mainly from the United States (82%). The interventions showed a 51% effectiveness in reducing weight, increasing physical activity, and changing eating habits. We conclude that coaching might be an effective therapeutic strategy for obesity and overweight.

Frequency analysis of the g.7081T>G/A and g.10872T>G polymorphisms in the FCGR3A gene (CD16A) using nested PCR and their functional specific effects.

Polymorphic variants p.66L>R/H (g.7081T>G/A; rs10127939) and p.176F>V (g.10872T>G; rs396991) in FCGR3A (CD16A) have been associated with defects in cytotoxic function of natural killer (NK) cells in humans. Genotyping of these variants in genomic DNA has been ambiguous because of high degree of homology between FCGR3A and FCGR3B. We designed a strategy to genotype these polymorphisms and to evaluate their effects on NK cells' cytotoxic activity. One hundred and fifteen individuals from different geographical regions of Colombia were included. Specific primers were designed to amplify FCGR3A exons 4 and 5 encompassing g.7081T>G/A and g.10872T>G by long-range and nested polymerase chain reaction and sequencing. The binding of different monoclonal antibodies to CD16A and NK antibody-dependent cellular cytotoxicity (ADCC) were evaluated. We demonstrate that amplifying and sequencing FCGR3A allows genotyping of g.7081T>G/A and g.10872T>G without interference from FCGR3B. Allele frequencies in our population were as follows: 7081T = 0.895, 7081G = 0.065, 7081 A = 0.039, 10872T = 0.673, and 10872G = 0.326. We also observed linkage disequilibrium between variants 7081T and 10872G. Interestingly, 176FF variant affected the reactivity of MEM154 monoclonal antibody against CD16A, but it did not affect ADCC. Our studies aimed to determine whether clinical association exists between these polymorphisms and NK cell function defects in patients with compatible phenotypes.

Tuberculosis and lung cancer.

OBJECTIVE: To describe the epidemiological studies about the relationship between lung cancer (LC) and pulmonary tuberculosis (Tb) and its possible molecular mechanisms. MATERIALS AND METHODS: We reviewed research databases in search of publications that included keywords LC and Tb. RESULTS: It has been proposed that chronic inflammation in the lungs due to Tb could cause clastogenic activity in the DNA of bronchial epithelium. Another possibility is lateral gene transfer; since Mycobacterium tuberculosis (MTb) is an intracellular organism, bacterial DNA could integrate to bronchial epithelial cells inducing neoplastic transformation. CONCLUSIONS: There are epidemiological reports, particularly from Asian countries, which confirm a relationship between LC and Tb. MTb could play an active role in cellular transformation and it is important to elucidate the mecha- nism involved.

OBJETIVO: Describir los estudios que documentan la relación entre el cáncer de pulmón (CP) y la tuberculosis pulmonar (Tb) y sus posibles mecanismos moleculares. MATERIAL Y MÉTODOS: Se revisaron bases de datos de publicaciones, usando como palabras clave CP y Tb. RESULTADOS: Se ha propuesto que la inflamación crónica en el pulmón provocada por la Tb podría producir actividad clastogénica. Otra posibilidad es la transferencia lateral de genes; Mycobacterium tuberculosis (MTb) es un organismo intracelular facultativo cuyo DNA podría integrarse al material genético del epitelio bronquial induciendo transformación neoplásica. CONCLUSIONES: Existen evidencias epidemiológicas, particularmente en países asiáticos, que documentan la relación entre CP y Tb. MTb podría desempeñar un papel activo en la transformación neoplásica cuyo mecanismo debe de ser elucidado.

Use of oral fluralaner for the treatment of Psoroptes cuniculi in 15 naturally infested rabbits.

BACKGROUND: Psoroptes cuniculi, a nonburrowing ear mite, is a common ectoparasite of rabbits. Constant irritation of the auditory canal by the presence of this mite can lead to otitis externa or otoacariasis. OBJECTIVE: The goal of this study was to evaluate the effect of fluralaner on rabbits naturally infested with P. cuniculi and exhibiting clinical signs. ANIMALS: Fifteen female New Zealand domestic rabbits with otitis due to naturally occurring infestation with P. cuniculi. METHODS: The external ears and ear canals of each individual were examined; samples of otic exudate were extracted with cotton swabs and examined microscopically for identification of the ectoparasite. Each animal was treated with a single 25 mg/kg oral dose of fluralaner. The amount of otic exudate/cerumen was assessed and samples were obtained from the ears to evaluate for presence or absence of mites at 4, 8, 12, 16, 20, 40 and 90 days after receiving treatment. RESULTS: Post-treatment, the amount of otic exudate decreased rapidly in all animals; by Day 12 and until the end of the study all rabbits were judged to have low amount of exudate with normally visible canals. The percentage of ears positive for P. cuniculi decreased to 13.3% of ears sampled by Day 4, and by Day 12 all rabbits were negative for the parasite. CONCLUSION: Administration of a single oral dose of fluralaner was effective for the treatment of naturally occurring P. cuniculi infestation in rabbits during a 90 day period.

Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

BACKGROUND: African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. OBJECTIVE: To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. ANIMALS: A 10-month-old African pygmy hedgehog weighing 184 g. METHODS: Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. RESULTS: On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. CONCLUSION AND CLINICAL IMPORTANCE: A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy.

Gene-expression profiles in lung adenocarcinomas related to chronic wood smoke or tobacco exposure.

BACKGROUND: Tobacco-smoke is the major etiological factor related to lung cancer. However, other important factor is chronic wood smoke exposure (WSE). Approximately 30 % of lung cancer patients in Mexico have a history of WSE, and present different clinical, pathological and molecular characteristics compared to tobacco related lung cancer, including differences in mutational profiles. There are several molecular alterations identified in WSE associated lung cancer, however most studies have focused on the analysis of changes in several pathogenesis related proteins. METHODS: Our group evaluated gene expression profiles of primary lung adenocarcinoma, from patients with history of WSE or tobacco exposure. Differential expression between these two groups were studied through gene expression microarrays. RESULTS: Results of the gene expression profiling revealed 57 statistically significant genes (p < 0.01). The associated biological functional pathways included: lipid metabolism, biochemistry of small molecules, molecular transport, cell morphology, function and maintenance. A highlight of our analysis is that three of the main functional networks represent 37 differentially expressed genes out of the 57 found. These hubs are related with ubiquitin C, GABA(A) receptor-associated like protein; and the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: Our results reflect the intrinsic biology that sustains the development of adenocarcinoma related to WSE and show that there is a different gene expression profile of WSE associated lung adenocarcinoma compared to tobacco exposure, suggesting that they arise through different carcinogenic mechanisms, which may explain the clinical and mutation profile divergences between both lung adenocarcinomas.

Efficacy of fluralaner in 17 dogs with sarcoptic mange.

BACKGROUND: There are few licensed options for the treatment of canine sarcoptic mange. OBJECTIVE: To evaluate the efficacy of fluralaner in dogs with sarcoptic mange infestation. ANIMALS: Seventeen dogs with a diagnosis of Sarcoptes scabiei based on positive skin scrapings. METHODS: A single dose of oral fluralaner was administered according to the manufacturer's instructions. Assessments of pruritus and lesions were performed every 7 days for 1 month. RESULTS: By Day 14 post-treatment, skin scrapings from all dogs were negative for mites. At the beginning of the study there was a negative correlation between body weight of the subject and pruritus [Pearson correlation coefficient (PCC) = -0.396, P = 0.007] and a positive correlation between pruritus and lesion severity (PCC 0.755, P = 0.0001). Significant decreases in lesion size and pruritus were observed within the first 14-21 days, respectively, and improvement in these parameters continued until the end of the study at Day 28. CONCLUSION: Fluralaner was effective in eliminating scabies mites within 14 days and significantly resolved the clinical signs associated with sarcoptic mange within 21 days after a single dose.

A novel pathogenic variant in PRF1 associated with hemophagocytic lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL2) results from mutations in PRF1. We described two unrelated individuals who presented with FHL, in whom severely impaired NK cytotoxicity and decrease perforin expression was observed. DNA sequencing of PRF1 demonstrated that both were not only heterozygous for the p.54R > C/91A > V haplotype but also presented with the novel variant p.47G > V at the perforin protein. Perforin mRNA was found to be increased in a individual with that genotype. A carrier of the novel variant also demonstrated altered perforin mRNA and protein expression. Phylogenetic analysis and multiple alignments with perforin orthologous demonstrated a high level of conservation at Gly47. PolyPhen-2 and PROVEAN predicted p.47G > V to be "probably damaging" and "deleterious", respectively. A thermodynamic analysis showed that this variant was highly stabilizing, decreasing the protein internal energy. The ab initio perforin molecular modeling indicated that Gly47 is buried inside the hydrophobic core of the MACPF domain, which is crucial for the lytic pore formation and protein oligomerization. After the in silico induction of the p.47G > V mutation, Val47 increased the interactions with the surrounding amino acids due to its size and physical properties, avoiding a proper conformational change of the domain. To our knowledge, this is the first description supporting that p.47G > V is a pathogenic variant that in conjunction with p.54R > C/91A > V might result in the clinical phenotype of FHL2.

Mapping mental health care services for children and youth population in Colombia's Pacific: potential for boundary spanning between community and formal services.

BACKGROUND: Conflict and violence can impact on the mental health of children and young people, who are in a crucial stage of their personal growth. Not much is known about the provision of mental health care to young people in conflict-affected areas. Community-based care can be essential, as state-led services are often scarce in conflict contexts, like Colombia's Pacific region where this research was conducted. According to the WHO, such care is ideally provided in the form of a network of interconnected services, offered by different actors beyond the formal health sector. This article describes the relationship between the formal and community mental health systems in Colombia's Pacific region, and identifies ways of improving their interaction. METHODS: Qualitative data were collected through 98 semi-structured interviews with community organisations, schools, international organisations and state institutions. These interviews aimed to identify the strategies used to promote young people's mental health and the interactions between the different providers. Boundary spanning theory was used to analyse how different actors and forms of mental health care provision could coordinate better. RESULTS: Community organisations and schools use a wide array of strategies to attend to the mental health of children and young people, often of a collective and psychosocial nature. State institutions offer more clinically focused strategies, which are however limited in terms of accessibility and continuity. International organisations aim to strengthen state capacity, but often struggle due to high staff turnover. Although mental health care pathways exist, their effectiveness is limited due to ineffective coordination between actors. CONCLUSIONS: To make sure that the variety of strategies to improve young people's mental health effectively reach their beneficiaries, better coordination is needed between the different actors. Mental health care pathways should therefore integrate community organisations, while community connectors can help to manage the coordination between different actors and forms of clinical and psychosocial support.

Functional Dizziness as a Spatial Cognitive Dysfunction.

(1) Background: Persistent postural-perceptual dizziness (PPPD) is a common chronic dizziness disorder with an unclear pathophysiology. It is hypothesized that PPPD may involve disrupted spatial cognition processes as a core feature. (2) Methods: A cohort of 19 PPPD patients underwent psycho-cognitive testing, including assessments for anxiety, depression, memory, attention, planning, and executive functions, with an emphasis on spatial navigation via a virtual Morris water maze. These patients were compared with 12 healthy controls and 20 individuals with other vestibular disorders but without PPPD. Vestibular function was evaluated using video head impulse testing and vestibular evoked myogenic potentials, while brain magnetic resonance imaging was used to exclude confounding pathology. (3) Results: PPPD patients demonstrated unique impairments in allocentric spatial navigation (as evidenced by the virtual Morris water maze) and in other high-demand visuospatial cognitive tasks that involve executive functions and planning, such as the Towers of London and Trail Making B tests. A factor analysis highlighted spatial navigation and advanced visuospatial functions as being central to PPPD, with a strong correlation to symptom severity. (4) Conclusions: PPPD may broadly impair higher cognitive functions, especially in spatial cognition. We discuss a disruption in the creation of enriched cognitive spatial maps as a possible pathophysiology for PPPD.

Analyses of the PRF1 gene in individuals with hemophagocytic lymphohystiocytosis reveal the common haplotype R54C/A91V in Colombian unrelated families associated with late onset disease.

Familial hemophagocytic lymphohistiocytosis (FHL), is a rare autosomal recessive disorder characterized by an impairment of cytotoxic cells and uncontrolled activation of macrophages. This study presents the first description of four patients with FHL type 2 in Latin America. Patient 1 fulfilled the disease diagnostic criteria since 2 months of age, whereas patients 2, 3 and 4 exhibited the typical manifestations of the disease only later in their childhood. The PRF1 genetic analysis in these patients revealed two previously reported mutations: L17fsx50 and R54C. Interestingly, seven out of the 8 alleles evaluated here in patients carried the haplotype R54C/A91V, suggesting that this is a highly frequent FHL type 2 allele in Colombia. This haplotype confers residual cytotoxic function leading to late onset disease. Therefore, this report highlights the remarkable complexity of FHL diagnostic, emphasizing the importance of the genetic characterization of the disease.

Social Support and Depressive Symptoms in the Context of COVID-19 Lockdown: The Moderating Role of Attachment Styles.

Objectives: COVID-19 sanitary measures (social distancing, school closures) have deeply impacted social life, support networks, and their protective role in mental health. The present study aims to understand how attachment styles influence the way individuals experience social support. Particularly, investigating its moderating role in the relationship between social support and depression. Methods: An online survey was designed to clarify the role of adult attachment styles (ECR-S) in the perceived social support (MOSS) and self-reported depressive symptoms (BDI-SF) in the COVID-19 context. Results: Positive social interactions was the most important dimension of social support for lower depression symptoms. Individuals attachment strategies have a moderating role in the relation between of social support and depression. Crucially, insecure attachment style wanes the positive impact of social support in depression. Conclusion: Aligned with the existing literature, attachment security is an essential factor in our current understanding of relationships and mental health. Exploring specific and indivual attachment strategies might be a powerful tool to protect population's mental healt.

Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients.

Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.

Sexual dimorphism in classical conditioning? Sex differences in neophobia, latent inhibition, generalization, and extinction for rats (Rattus norvegicus) in a conditioned taste aversion preparation irrespective of housing conditions.

This study aimed to assess possible sex differences and a potential impact of social housing conditions for some Pavlovian conditioning effects in a conditioned taste aversion preparation with rats. The results of Experiment 1 suggest sex differences in neophobia, latent inhibition, and generalization. Specifically, for females, neophobia, and generalization appeared to be stronger while latent inhibition seemed to be attenuated. Experiment 2 confirmed these sex differences in neophobia and generalization, while also revealing slower extinction in males. Experiment 3 provided evidence for the same sex differences in neophobia and generalization, even when a perceptual learning effect was in operation following pre-exposures to the test stimulus. No effects of social housing conditions were found in either Experiment 1 or Experiment 2. In general, these findings appear to support the hypothesis of sexual dimorphism in Pavlovian conditioning, encouraging a systematic approach to the topic by means of further research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Social Support and Cognition: A Systematic Review.

Although the influence of social support in health is a widely acknowledged factor, there is a significant gap in the understanding of its role on cognition. The purpose of this systematic review was, therefore, to determine the state-of-the-art on the literature testing the association between social support and cognition. Using six databases (WoS, PubMed, ProQuest, PsycINFO, Scopus and EBSCOhost), we identified 22 articles published between 1999 and 2019 involving an empirical quantitative focus which meet the inclusion criteria. Data extraction was performed following PRISMA recommendations. To summarize the extracted data, we used a narrative synthesis approach. Despite limitations, there is overall preliminary evidence of a relevant positive association between social support and cognition. Our results demonstrate there is enough information for an outbreak of experimental research in the area and an expansion of this body of knowledge. We argue that the present evidence lays the foundations for a more comprehensive theoretical model, one that corresponds with the complexity of the topic and possibly considers models derived from social interaction and active inference theories.

Impact of detecting plasma EGFR mutations with ultrasensitive liquid biopsy in outcomes of NSCLC patients treated with first- or second-generation EGFR-TKIs.

BACKGROUND: Few trials have evaluated the utility of liquid biopsies to detect epidermal growth factor receptor mutations (EGFRm) at the time of response evaluation and its association with the clinical characteristics and outcomes of non-small-cell lung cancer (NSCLC) patients. OBJECTIVE: This study aimed to evaluate, in a real-world clinical setting, the prevalence of plasma EGFRm and its association with the clinical characteristics, response and survival outcomes of NSCLC patients under treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This observational study enrolled advanced or metastatic NSCLC patients, with confirmed tumor EGFRm, receiving treatment with first- or second-generation EGFR-TKIs. Blood samples for the detection of plasma EGFRm were collected at the time of response evaluation and processed using the Target Selector™ assay. The main outcomes were the detection rate of plasma EGFRm, median Progression-Free Survival (PFS) and Overall Survival (OS) according to plasma EGFR mutational status. RESULTS: Of 84 patients, 50 (59.5%) had an EGFRm detected in plasma. After a median follow-up of 21.1 months, 63 patients (75%) had disease progression. The detection rate of plasma EGFRm was significantly higher in patients with disease progression than in patients with partial response or stable disease (68.3% versus 33.3%; P< 0.01). PFS and OS were significantly longer in patients without plasma EGFRm than among patients with plasma EGFRm (14.3 months [95% CI, 9.25-19.39] vs 11.0 months [95% CI, 8.61-13.46]; P= 0.034) and (67.8 months [95% CI, 39.80-95.94] vs 32.0 months [95% CI, 17.12-46.93]; P= 0.006), respectively. A positive finding in LB was associated with the presence of ⩾ 3 more metastatic sites (P= 0.028), elevated serum carcinoembryonic (CEA) at disease progression (P= 0.015), and an increase in CEA with respect to baseline levels (P= 0.038). CONCLUSIONS: In NSCLC patients receiving EGFR-TKIs, the detection of plasma EGFRm at the time of tumor response evaluation is associated with poor clinical outcomes.