Detection of Tumor-Associated Membrane Receptors on Extracellular Vesicles from Non-Small Cell Lung Cancer Patients via Immuno-PCR

Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is challenging, and metastatic lesions may have heterogeneous signaling. One way ahead is to use liquid biopsies such as circulating tumor DNA or small extracellular vesicles (sEVs) secreted by the tumor into blood or other body fluids. Herein, an immuno-PCR-based detection of the tumor-associated membrane receptors EGFR, HER2, and IGF-1R on CD9-positive sEVs from NSCLC cells and pleural effusion fluid (PE) of NSCLC patients is developed utilizing DNA conjugates of antibody mimetics and affibodies, as detection agents. Results on sEVs purified from culture media of NSCLC cells treated with anti-EGFR siRNA, showed that the reduction of EGFR expression can be detected via immuno-PCR. Protein profiling of sEVs from NSCLC patient PE samples revealed the capacity to monitor EGFR, HER2, and IGF-1R with the immuno-PCR method. We detected a significantly higher EGFR level in sEVs derived from a PE sample of a patient with an EGFR-driven NSCLC adenocarcinoma than in sEVs from PE samples of non-EGFR driven adenocarcinoma patients or in samples from patients with benign lung disease. In summary, we have developed a diagnostic method for sEVs in liquid biopsies of cancer patients which may be used for longitudinal treatment monitoring to detect emerging bypassing resistance mechanisms in a noninvasive way.

Spatial distribution of children used Ritalin at the neuropediatrics clinic in Maringá (PR), Brazil

Blackground Brazil is the second largest consumer of methylphenidate in the world. Considering the social determinants on the health of people and communities, the objective of the research is to evaluate the influence of social and economic factors on the prescription of methylphenidate for school-age children. Methods Quantitative exploratory study with primary data collected from the electronic medical records of school-aged children, 6 to 11 years old, in a neuropediatric clinic at a Basic Health Unit of the Unified Health System (SUS) in a city located in the southern region of Brazil, with the date of the last withdrawal of methylphenidate between the period of March 2017 to November 2019. Results 104 patients who used methylphenidate were evaluated, 85 male and 19 female, with an average age of 8.26 years at the outpatient clinic and 9.19 years currently, the youngest being 6 years old and the largest 11 years old, with deviation 1.47 standard. Preliminary results indicate that 50.96% of prescriptions were aimed at children from places of greatest social vulnerability. Conclusions It was found that the majority of school-age children prescribed ritalin at the clinic are from poor neighborhoods. Building this panorama based on socioeconomic determinants suggests the need to understand the influence of how environments with higher levels of violence can influence the health-disease process, both for integrality to diagnosis and for longitudinality to treatment. New studies are suggested that consider children who have not been treated in the public health service. Key messages Impact of the evaluation of socioeconomic determinants on the prescription of methylphenidate for school-age children. Integral and longitudinal treatment with methylphenidate for children from poor areas.

Disease and Treatment Patterns Among Patients With Pouch-related Conditions in a Cohort of Large Tertiary Care Inflammatory Bowel Disease Centers in the United States

Background Gaps exist in our understanding of the clinical course of pouch-related disorders. Methods We evaluated baseline disease activity and longitudinal treatment patterns among patients with inflammatory conditions of the pouch. Results Among 468 patients with an ileal pouch-anal anastomosis (IPAA), 94 (20%) had acute pouchitis, 96 (21%) had chronic pouchitis, and 192 (41%) had Crohn disease of the pouch. Following an IPAA, 38% of patients were treated with a biologic and 11% underwent inflammatory bowel disease- or bowel-related surgery. Conclusions Treatment patterns after IPAA indicate that pouch-related disorders have a significant impact on individual patients and the healthcare system.