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

Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid

Background Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease. Yet, such knowledge is important for a quantitative understanding of tissue synthesis and degradation. Methods We have measured the accumulation of d-Asp and pentosidine in IVD elastin. Samples representing a broad range of ages (28–82 years) and degeneration grades (1–5) were analyzed. Results d/l-Asp for elastin increased linearly with age from 3.2% (early 30s) to 14.8% (early 80s) for normal tissue (grades 1–2) and from 1.7% (late 20s) to 6.0% (until the mid 50s) for degenerate tissue (grades 3–5) with accumulation rates of 16.2 ± 3.1 × 10− 4 and 11.7 ± 3.8 × 10− 4 year− 1, respectively; no significant difference was found between these values (p < 0.05). Above the mid 50s, a decrease in d-Asp accumulation was recorded in the degenerate tissue. d-Asp accumulation correlated well with pentosidine content for elastin from healthy and degenerate tissues combined. We conclude that IVD elastin is metabolically‐stable and long‐lived in both healthy and degenerate human IVDs, with signs of new synthesis in the latter. The correlation of d‐Asp with pentosidine content suggests that both these agents may be used as markers in the overall aging process of IVD. General significance Accumulation of modified IVD elastin argues for its longevity and may have a negative impact on its role in disc function. Weak signs of newly synthesized molecules may act to counteract this effect in degenerate tissue