Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Вплив Ag на поверхневий стан TiO2, оптичну активність та його цитотоксичність

Наночастинки (НЧ) Ag/TiO2 було отримано простим методом хімічного осадження з використанням нітрату срібла та суспензії TiO(OH)2. Частинки срібла осаджували як на поверхні, так і в самих частинках TiO2 в залежності від концентрації Ag. Композити Ag/TiO2 були охарактеризованi рентгенівською дифракцією, просвітлючою електронною мікроскопією, скануючою електронною мікроскопією, раманівською та фотолюмінесцентною спектроскопією. Клітинна життєздатність оцінювалась за допомогою аналізу МТТ (3-(4,5-диметилтіазол-2-іл)-2,5-дифенілтетразолію бромід) після впливу НЧ. Показано оптичну активність Ag/TiO2 зі зсувом моди Еg від 143 до 150 см – 1 та FWHM від 12 до 19 см – 1 внаслідок зменшення кристалітів TiO2. Оптична активність зростає зі збільшенням концентрації Ag до 8 мас. %. У зоні контакту Ag-TiO2 утворюється бар'єр Шотткі, що покращує розподіл заряду і таким чином уповільнює рекомбінацію фотогенерованих електронів та фотогенерованих дірок. Отримані результати свідчать про меншу токсичність НЧ у суспензії гліцерин + вода, незалежно від введення молекул срібла в кількості 4 або 8 мас. %, їх значення CC50 становили 50 та 3,9-58,5 мкг/мл для клітин MDBK (нирки бика) та MDCK (нирки собаки) відповідно. Натомість НЧ TiO2, розчинені в C2H5OH+ 1,3-пропандіолі при введенні молекул срібла, були значно більш токсичними для клітин MDBK у порівнянні з чистим TiO2, їх значення CC50 становили 6,5 та 4 мкг/мл. Одержані НЧ Ag/TiO2 внаслідок їх оптичної активності будуть досліджені як протигрибковий матеріал для інгібування бактерій та вірусів у воді.Ag/TiO2 nanoparticles (NPs) were prepared by a simple chemical deposition method using silver nitrate and suspension of TiO(OH)2. Silver NPs were deposited on the surface and inside of TiO2 NPs depended on the Ag concentration. The Ag/TiO2 composites were characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and Raman spectroscopy. The cell viability was assessed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after NPs exposure, since only viable cells have functional mitochondrial dehydrogenase enzymes that can reduce MTT to formazan. The shift of the Eg mode from 143 to 150 cm – 1 and FWHM from 12 to 19 cm – 1 was stated due to a decrease in TiO2 crystallites. Optical activity increased after loading with Ag because metal particles offered electron traps to reduce recombination of holes and electrons, especially Ag loading of 8 wt. %. A Schottky barrier is formed in the Ag-TiO2 contact region, which improves charge separation and thus slows down the recombination of photogenerated electrons and photogenerated holes. The obtained results indicate a lower toxicity of NPs in a glycerin + water suspension, regardless of the introduction of silver molecules in an amount of 4 or 8 wt. %, their CC50 values were 50 and 3.9-58.5 µg/ml for MDBK and MDCK cells, respectively. The obtained Ag/TiO2 NPs due to their optical activity will be examined as an antifungal material for the inhibition of bacteria and viruses in water

Global Retinoblastoma Presentation and Analysis by National Income Level

This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis. Key PointsQuestionIs the income level of a country of residence associated with the clinical stage of presentation of patients with retinoblastoma? FindingsIn this cross-sectional analysis that included 4351 patients with newly diagnosed retinoblastoma, approximately half of all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from low-income countries had extraocular tumor at time of diagnosis compared with 1.5\% of patients from high-income countries. MeaningThe clinical stage of presentation of retinoblastoma, which has a major influence on survival, significantly differs among patients from low-income and high-income countries, which may warrant intervention on national and international levels. ImportanceEarly diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. ObjectivesTo report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and ParticipantsA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and MeasuresAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. ResultsThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs