Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients

© The Author(s) 2019. Published by Springer Nature on behalf of Cancer Research UK.BACKGROUND: An accurate and simple risk prediction model that would facilitate earlier detection of pancreatic adenocarcinoma (PDAC) is not available at present. In this study, we compare different algorithms of risk prediction in order to select the best one for constructing a biomarker-based risk score, PancRISK. METHODS: Three hundred and seventy-nine patients with available measurements of three urine biomarkers, (LYVE1, REG1B and TFF1) using retrospectively collected samples, as well as creatinine and age, were randomly split into training and validation sets, following stratification into cases (PDAC) and controls (healthy patients). Several machine learning algorithms were used, and their performance characteristics were compared. The latter included AUC (area under ROC curve) and sensitivity at clinically relevant specificity. RESULTS: None of the algorithms significantly outperformed all others. A logistic regression model, the easiest to interpret, was incorporated into a PancRISK score and subsequently evaluated on the whole data set. The PancRISK performance could be even further improved when CA19-9, commonly used PDAC biomarker, is added to the model. CONCLUSION: PancRISK score enables easy interpretation of the biomarker panel data and is currently being tested to confirm that it can be used for stratification of patients at risk of developing pancreatic cancer completely non-invasively, using urine samples.Peer reviewe

Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children

Background: Whether long coronavirus disease pertains to children as well is not yet clear. Methods: The authors performed a survey in children suffering from persistent symptoms since initial infection. A total of 510 children infected between January 2020 and January 2021 were included. Results: Symptoms such as fatigue, headache, muscle and joint pain, rashes and heart palpitations and issues such as lack of concentration and short-term memory problems were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. Conclusion: A better comprehension of long coronavirus disease is urgently needed

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers : A Systematic Review and Meta-Analysis

Funding This research was funded by Rosetrees Trust, grant number CF1\100001, and Barts Charity, grant number ECMG1C3R. The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.Peer reviewedPublisher PD

TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p < 0.01) and KREC with CD19 (r = 0.56, p < 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis

Quality of life associated with maternal anxiety disorder in Russian children and adolescents with food allergy

Background: Food allergy negatively impacts the quality of life (QoL) and has been associated with increased maternal anxiety. There is currently a lack of data assessing QoL of food‐allergic children and adolescents in Russia. We aimed to evaluate the performance of the Food Allergy Quality of Life Questionnaire (FAQLQ) measures in a Russian sample of children, adolescents, and mothers and to investigate association between child QoL and maternal general anxiety. Methods: FAQLQ and Food Allergy Independent Measures (FAIM) were translated to Russian to be completed by participants. Mothers also filled the General Anxiety Disorder (GAD‐7) questionnaire. Reliability, construct, and discriminant validity of the FAQLQs and association between FAQLQ scores and general anxiety were assessed. Results: A total of 142 participants completed FAQLQ and FAIM. In total, 126 mothers completed GAD‐7 questionnaire. All FAQLQs showed excellent internal consistency (α > 0.94). The means for the FAQLQ‐PF, FAQLQ‐CF, and FAQLQ‐TF varied according to the number of foods avoided, severity of symptoms, and FAIM and GAD scores (ηp2 0.40 P < .001). One in 5 mothers had GAD‐7 score indicative of moderate‐to‐severe anxiety. Association strength between GAD and FAQLQ increased with age. GAD score was associated with FAQLQ‐PF score, controlling for multiple confounders. Conclusion: The FAQLQ showed good reliability and validity in Russian. This study identified number of foods avoided and reported reaction severity being associated with greater QoL impairment in Russian children and adolescents affected by food allergy. The significant association found between general anxiety in parents and QoL in children and adolescents has practice, screening, and resource implications. Key Message: This study found that 1 in 5 mothers of Russian food‐allergic children in given cohort had generalised anxiety disorder (GAD‐7) questionnaire score indicative of moderate to severe anxiety. This is three times higher than in general population norms. A third of mothers were above the threshold score for panic and social anxiety disorders. Relationship strength between maternal general anxiety and FAQLQ increased with age. Associations between the GAD‐7 score and parental form of FAQLQ score. Our results will add to ongoing work in the development of food allergy normed age scores to allow for precise measurement, interpretation of scores, and comparison across countries and cultures

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate.

The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.post-print6382 K