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Metastasis is the major cause of death in cancer patients accounting for about 90% of the mortality. The detection and analysis of the hallmark of metastasis, circulating tumor cells (CTCs), have significant impact in cancer biology and clinical practice. However, the scarcity of CTCs in blood, particularly in that of colorectal cancer patients, is a serious bottleneck in the development of CTC-based precision medicine. Herein, the melt electrowriting (MEW) technology was used for reproductive fabrication of a biocompatible antibody-presenting polycaprolactone filter with tailored porous structure. It is demonstrated, for the first time, that such filter can be used not only to catch cancer cells spiked in whole blood but also to culture the cancer cells directly on site. Specifically, HT29 colon cancer cells can be captured with an efficiency of 85%, and when spiked into 4 mL of whole blood, 47% were captured on one Ø12mm filter. Furthermore, repeated capture and culture experiments have shown that as few as 20 HT29 colon cancer cells spiked into 4 mL of whole blood can be captured on the filter and within 2 weeks be expanded on site to become tumor bodies that are visible to the untrained eye. This filter allows for downstream analysis, such as flow cytometry, immunocytochemistry, Western blotting, and rt-qPCR. This technology represents a simple and cost-effective platform that potentially enables fast and efficient culture of rare CTCs from patients’ blood. This provides non-invasive alternatives for solid biopsy tumor materials for treatment screening, with great potential to realize precision medicine for cancer treatment.

Respiratory allergy often begins in childhood and most commonly manifests as allergic rhinitis (upper airways) and/or asthma (lower airways). Children with upper respiratory allergy often suffer from coexisting asthma, and other comorbidities ranging from gastrointestinal disorders to emotional/mental health disorders. Consequently, the disease burden is considerable and profoundly impacts a child's daily life. Early identification and appropriate management are important to reduce disease burden, lower the risk of disease progression and additional comorbidities, and protect the child's future well-being. A window of opportunity for halting disease progression may open in the early stages of allergic disease and underlines the importance of early diagnosis and treatment of children at risk. This review offers advice on identifying children with a high disease burden who would benefit from early intervention. Allergen immunotherapy (AIT) modifies the cause of respiratory allergy and prevents disease progression. In clinical practice, AIT could be considered as an early treatment for eligible children, to achieve long-term symptom control and disease modification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. EH has received grants from the German Ministry of Education and Research (BMBF), Network University Medicine (NUM), Ministry of Health and Social Affairs of Nordrhein-Westfalen (MAGS), and Federal Joint Committee (G-BA), and has received fees for lectures and consulting activities from Abbvie, Aimmune, ALK-Abelló, Allergopharma, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, DBV, GSK, LETI Pharma, Novartis, Nutricia, nutrimmun, Sanofi, and Stallergenes. EH is the Vice President of the German Allergy Society (DGAKI) and the President of the German Asthma Net (GAN e.V.). PC has received fees for consulting activities from ALK-Abelló, Thermo Fisher Scientific, Orion Pharma, and GSK. GR has received fees for lectures and consulting activities from ALK-Abelló, research support from AstraZeneca, and has been supported by Allergen Therapeutics. CV has received grants from the German Research Foundation (DFG), and has received fees for lectures and consulting activities from Abbvie, Aimmune, ALK-Abelló, Allergopharma, AstraZeneca, Allergy Therapeutics, Bencard Allergie, Boehringer Ingelheim, DBV, LETI Pharma, Novartis, Orion Pharma, Sanofi Aventis, and Stallergenes. EC-J is a member of the ALK-Abelló Paediatric Advisory Board and has received fees for lectures and consulting activities from ALK-Abelló, Stallergenes-Greer, GSK, Thermofisher Scientific, and Allergopharma. JJ is a member of the ALK-Abelló Paediatric Advisory Board and has received fees for lectures and consulting activities from ALK-Abelló, Stallergenes-Greer, GSK, Novartis, AstraZeneca, and Zambon. MJ has received consultancy/speaker honoraria from ALK-Abelló, Berlin-Chemie, Stallergenes-Greer, GSK, and Viatris, and is a member of Advisory Boards for ALK-Abelló, Stallergenes-Greer, and Viatris., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To characterize peripheral nerve morphology in cerebrotendinous xanthomatosis (CTX) patients using high-resolution ultrasound (HRUS) in vivo. We hypothesized that nerve enlargements might be present in CTX as a result of accumulation of abnormal lipids with deposition also in peripheral nerves., Methods: Four CTX patients were examined using HRUS to assess morphological abnormalities of peripheral nerves as well as cervical nerve roots 5 and 6., Results: HRUS revealed mild to moderate, hypoechogenic thickening of sensorimotor nerves (ulnar nerve in 1/4, tibial nerve in 3/4, median nerve 4/4 patients) as well as mild enlargement of pure sensory nerves (sural nerve in 2/3, superficial FN in 2/4 patients). The vagal nerve was moderately enlarged in one patient, cervical roots showed moderate enlargements of C5 in two patients, one of which also showing thickening of C6 as well as in another patient. UPSS score was slightly to moderately abnormal in all patients. The Homogeneity score was not increased suggesting regional to inhomogeneous nerve enlargement., Conclusions: HRUS shows multifocal, hypoechogenic nerve thickening of peripheral nerves and nerve roots in CTX., Significance: HRUS might serve as a valuable, additive and non-invasive bedside tool to assess peripheral nerve morphology in future clinical studies on CTX patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Brain-computer interfaces (BCIs) are often based on the control of sensorimotor processes, yet sensorimotor processes are impaired in patients suffering from amyotrophic lateral sclerosis (ALS). We devised a new paradigm that targets higher-level cognitive processes to transmit information from the user to the BCI. We instructed five ALS patients and twelve healthy subjects to either activate self-referential memories or to focus on a process without mnemonic content while recording a high-density electroencephalogram (EEG). Both tasks are designed to modulate activity in the default mode network (DMN) without involving sensorimotor pathways. We find that the two tasks can be distinguished after only one experimental session from the average of the combined bandpower modulations in the theta- (4-7Hz) and alpha-range (8-13Hz), with an average accuracy of 62.5% and 60.8% for healthy subjects and ALS patients, respectively. The spatial weights of the decoding algorithm show a preference for the parietal area, consistent with modulation of neural activity in primary nodes of the DMN., (© 2016 Elsevier B.V. All rights reserved.)

Background: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years., Methods: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years., Findings: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years., Interpretation: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma., Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used., Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains., Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The prevalence of asthma and allergic diseases has increased world-wide during the last quarter of the 20th century, particularly among children and adolescents. No change common to all sites where asthma has increased throughout the world has been identified, suggesting that this 'epidemic' phenomenon is likely due to multiple factors. The following have been most discussed: exposure to indoor and outdoor allergens, modification of the patterns of respiratory infections, decreasing trends of physical activity, evolution in the make-up of environmental irritants, including tobacco smoke and urban air toxicants. In this review, we point out the role of exposure to air pollutants, in addition to and in combination with other asthma enhancers or precipitators. Whereas concentrations of the 'classical' air quality indicators (SO2, CO) have more or less steadily decreased, asthma prevalence augmented in developed countries during the same period. However, the nature of the air pollution mix has deeply evolved, and should also be considered. Ambient air concentrations of industrial and house heating combustion sources of pollutants in the city have substantially decreased, but by contrast the concentrations of various ultrafine particles have increased. Now, there is in vitro and in vivo evidence that exposure to urban air particles, and particularly to diesel exhausts, elicits chronic oxidative stress and repeated inflammatory responses, so that they may enhance allergic inflammation and airway hyper-responsiveness. Several epidemiological studies suggested an association between traffic density close to places of children's residence and prevalence of respiratory symptoms, and more specifically of asthma or allergic rhinitis symptoms in them. Chronic exposure during infancy to traffic-related pollutants may accelerate or even provoke, among genetically sensitive subjects, disruption of the normal regulatory and repair processes eventually contributing to the increase of asthma incidence.

Background: Improving anemia in patients with chronic renal failure (CRF) and congestive heart failure (CHF) also improves left ventricular hypertrophy (LVH). No previous meta-analyses have been conducted to further examine this association, including the association between LVH and mortality in these patients., Methods and Results: Literature searches on MEDLINE, EMBASE, and OVID were performed using Cochrane Library protocols. Two hundred sixteen abstracts were reviewed preliminarily for inclusion in the meta-analysis of epoetin alfa, anemia and 5 pre-selected parameters of LVH. One hundred seventy-nine abstracts were reviewed for LVH and mortality. The predominant hematologic and left ventricular function changes observed during epoetin alfa treatment in patients with CHF and CRF are (1) increases in hemoglobin (Hb) and hematocrit (Hct); (2) decreases in left ventricular mass (LVM) and LVM index; (3) increase in ejection fraction (EF); and (4) decreases in left ventricular end-diastolic and end-systolic volume. Three independent factors-target Hb, duration of disease, and duration of follow-up-each had a statistically significant association with Hb, Hct, and EF, respectively. A separate meta-analysis using 3 risk models showed LVH is strongly and positively associated with both cardiovascular and all-cause mortality, with two- to three-fold increases in risk., Conclusions: LVH is common in patients with CRF and CHF. Current findings indicate epoetin alfa therapy results in anemia amelioration, as evidenced by higher Hb and Hct levels, and reduction of key LVH parameters. LVM regression is associated with lower incidence of cardiovascular-related morbidity and mortality, therefore epoetin alfa therapy may provide a survival benefit.

Recurrent respiratory tract infections are a common reason for visits to primary care practitioners or hospital physicians. They are placed at the junction of several medical specialities: paediatrics, ENT, pneumology, allergology, immunology, infectiology. The great diversity of the laboratory tests requested and on the other hand the proposed treatments, are the consequences of the diversity of the patients encountered and the paucity of the evidence based-medicine studies in this setting. The dilemma is how to identify the child for which recurrent respiratory tract infections are the witness of underlying condition, without performing repeated medical examinations, laboratory tests and treatments for normal children for which immunologic development occurs normally. The essential tools are the history analysis, physical examination and few laboratory tests. The other questions are how to include, for these patients, influenza and pneumococcal vaccines in the immunization program and how to assess the benefit/risk ratio and the cost of surgical treatments. This paper presents the thought of an expert group trying to define the situations where biological tests or treatments are useful.

Specific immunotherapy involves the administration of allergen extracts to achieve clinical tolerance of the allergens which cause symptoms in patients with allergic conditions. Immunotherapy has been shown to be effective in patients with mild forms of allergic diseases, specially in upper airway diseases. Recent studies suggest that specific immunotherapy may also modify the course of allergic disease, by reducing the risk of developing new allergic sensitizations, and also inhibiting the development of clinical asthma in children treated for allergic rhinitis. The traditional subcutaneous route is burdened with the risk of severe adverse events, therefore, local routes have been investigated and developed. The sublingual route is supported by numerous controlled trials showing its efficacy in rhinitis. The safety profile, assessed in clinical trials studies, is satisfactory. Several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence. New approaches using mimic bacterial DNA vaccines alone or associated to modified allergen, which enhances immunogenicity in terms of eliciting a Th1-type response vaccines, are also undergoing serious consideration.

Several studies among adult populations showed that an array of outdoor and indoor sources of particles emissions contributed to personal exposures to atmospheric particles, with tobacco smoke playing a prominent role (J. Expo. Anal. Environ. Epidemiol. 6 (1996) 57, Environ. Int. 24 (1998) 405, Arch. Environ. Health 54 (1999) 95). The Vesta study was carried out to assess the role of exposure to traffic emissions in the development of childhood asthma. In this paper, we present data on 68 children aged 8-14 years, living in the metropolitan areas of Paris (n = 30), Grenoble (n = 15) and Toulouse (n = 23), France, who continuously carried, over 48 h, a rucksack that contained an active PM2.5 sampler. Data about home indoor sources were collected by questionnaires. In parallel, daily concentrations of PM10 in ambient air were monitored by local air quality networks. The contribution of indoor and outdoor factors to personal exposures was assessed using multiple linear regression models. Average personal exposure across all children was 23.7 microg/m3 (S.D. = 19.0 microg/m3), with local means ranging from 18.2 to 29.4 microg/m3. The final model explains 36% of the total between-subjects variance, with environmental tobacco smoke contributing for more than a third to this variability; presence of pets at home, proximity of the home to urban traffic emissions, and concomitant PM10 ambient air concentrations were the other main determinants of personal exposure.

The prevalence of respiratory allergies has increased over the last 20 years, highlighting the need for a simple and noninvasive tool to investigate, in a clinical and epidemiological context, airway-inflammation mechanisms encountered in allergic and inflammatory processes. The nose, as the first region of the respiratory tract to come in contact with airborne pollutants, is easily explored with the use of nasal lavage (NL). We evaluated an NL method for adults and children, along with its reproducibility and capacity to separate different subgroups. NL reproducibility, assessed in 10 healthy, nonsmoking adults on three different occasions, was determined with the use of the intraclass coefficient of correlation for such inflammatory markers as total cell count, albumin, urea, neutrophil elastase, alpha(1)-antitrypsin, interleukin-6, and interleukin-8. Using this NL method, we analyzed nasal markers of 50 healthy adults (smokers and nonsmokers) and 12 healthy children. Our NL method demonstrated high reproducibility with regard to total cell count, albumin, urea, and alpha(1)-antitrypsin (intraclass correlation coefficient > 0.75). Compared with NL results in nonsmokers, NL in heavy smokers revealed significant increased concentrations of total cell counts and interleukin-8 and significant decreased concentrations of interleukin-6. These findings suggest that NL can be used as a tool in the assessment of inflammation because it has the correct reproducibility and can discriminate between heavy smokers and nonsmokers. Moreover, the use of this standardized method in children is feasible.

Increase of the prevalence of allergy these last 20 years is in part secondary to the modification of the allergenic charge of our environment. The specific immunotherapy (SIT) is the only etiologic treatment of the allergic disease and numbers of authors believe that, for the future, this treatment could change the natural history of the respiratory allergy, provided that it is realised early in the first years of life. Several experimental studies show that the process of the SIT could be the restoration of the Th1 cell/Th2 cell balance which is reversed in allergies. However, indications of SIT have to be carefully selected. The ideal indication is the single sensitized asthma, and treatment has to be started in the first years of life, at the onset of the asthmatic disease, before a definitive remodelling of the respiratory airways induced by inflammation. Subcutaneous SIT is for the moment the only effective route confirmed by several controlled trials, in particular for grass pollens, possibly for house dust, pet danders and mite allergens. Risk of syndromic effects, present all the time of the SIT protocol, can be prevented by rigorous use of the SIT according to the European consensus. The advent of recombinant allergens, in particular by complementary DNA (cDNA) modified by site-directed mutagenesis, could tip the immune response to a Th-1 like response instead of a Th-2 like response (IgE mediated) and result in a better tolerated and more efficacy immunomodulation.