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

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Antifeedant and Cytotoxic Activity of Longipinane Derivatives

6 pages, figures, and tables statistics.The polyoxygenated longipinane derivatives 1–8 were tested as antifeedant compounds against the herbivorous insects Spodop- tera littoralis, Rhopalosiphum padi, and Myzus persicae. Compounds 1–3 and 8 exhibited significant antifeedant activity against S. littoralis and M. persicae. The antifeedant activity against S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed to afford 1 and increased strongly after the remaining two hydroxy groups were acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and 4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca sativa.When tested on a panel of tumoral cells, compounds 2 and 6 exhibited moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299, which were not affected by the drug paclitaxel. In addition, vibrational circular dichroism (VCD) was applied to the representative longipinene derivative 2 to verify its absolute configuration, and the sensitivity of the VCD methodology was evaluated by comparing spectra of the three diastereoisomers (4R,5S,7R,9R,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4R,5S,7S,9R,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one, and (4R,5S,7R,9S,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one.Peer reviewe

Anales de Edafología y Agrobiología Tomo 41 Número 9-10

Suelos. Características petroquímicas y micromorfológicas de Haploxeralfs, por P. Arévalo. J. Gallardo y J. Benayas.-- Determinación de manganeso total en suelos, por J. Moreno Caselles, M. Guillén y M. Romero.-- Rendolles de la Sierra de María (Almería), por L J. Alias y J. Martínez.-- Estudio de tres perfiles de suelos de La Alpujarra, por Barahona. E., García Chicano. J. L. Guardiola. J. L. lriarte. A, Pérez-Pujalte, A. y Quirantes, J.-- Detección de concordancias fisonómico-edáficas por J. M. Gómez. R. Rodríguez González. A. García Miranda y C. de Hoyos Alonso.-- Suelos y sedimentos de zonas semiáridas, por A. García Rodríguez, J. Forteza Bonnin y L F. Lorenzo Martín.-- Suelos sobre jumillita de la Sierra de las Cabras (Albacete), por Joaquín Hernández Bastida, María Teresa Fernández Tapia y Francisco Alcaraz Ariza.-- Estudio microscópico de aridisoles de las Islas Canarias, por A. Rodríguez Rodríguez, M. C. Pérez Angles. M. C. Díez de la Lastra Bosch y E. Fernández Caldas.-- El material original: propiedades de los suelos de Galicia, por F. Macias. R. M. Calvo, C. García. E. García-Rodeja y B. Silva.-- Las sierras de Queixa e invernadeiro y sus estribaciones, por Grupo de Edafólogos de Santiago.-- Suelos forestales de la cordillera costero-catalana, por A. Escuredo. V. R. Vallejo y J. Bech.-- Materia orgánica de suelos forestales, por A. Escuredo. V. Vallejo y J. Bech.--Dificultades en el empleo del sistema "USDA-Soil Taxonomy", por Carlos Roquero de Laburu.-- Nematodos fitoparásitos de la superfamilia "criconematoidea", por A. Bello y Ma. Paz Lara.—Silicatos. Retención del diazinon por montmorillonita, sepiolita y caolinita, por G. Dios Cancela, S. González García y M. Martín Aguilar.—Geoquímica. Alteración de minerales de estaño, por Guijarro, J. Casas, J. y Hoyos, M.A.—Nutrición y Fisiología Vegetal.-- Capacidad fotosintética de maíz, por U. Velázquez, M. Lasaña y J. Cardus.-- El alerce en Chile. II. Su nutrición mineral, por M. Lachica, C. González O. y M. Baez. C. Anomalías por deficiencias de Ca o de Mg en raíces de plantas de zea mays L., por José Manuel Pozuelo Guanche.-- Competencia de avena sterilis L .. por R. González Ponce.-- Abcisión de las hojas de phaseolus vulgaris, por Ana María Vieitez y María Luisa Vieitez. El castaño y su resistencia a phytophthora cinnamomi y Ph. cambivora, por Ernesto Vieitez, María Luisa Vieitez y Ana María Vieitez.-- Observaciones sobre el injerto juvenil.del castaño, por María Luisa Vieitez y Ana María Vieitez.-- Crecimiento y nutrición del trébol violeta, por J. Arines y R. Fábregas.-- La proliferación celular en meristemos. por G. Giménez-Manín, J. F. López-Sáez, A. González-Fernández. C. de la Torre y M. H. Navarrete.—Microbiología.-- Formaciones quiméricas anómalas en cultivos bacterianos, por Román de Vicente. Análisis.-- Determinación de fenoles y formas de N en aguas, por Bolarin, M. C. Romero, M. y Caro, M.-- Agua Reutilización de aguas y lodos residuales. I., por Sa/got, M. y Cardus, J. II por Felipo M. T., Garau, M. A., Pascual, M. D. y Cardus, J.-- Ecología. Aspectos ecológicos de sotos y riberas, por Pedro Montserrat Recoder.-- Control Sanitario.Evolución de clorobencilato en brotes de limonero, por J. Ma. Abrisqueta, A. Onuño, J. Gómez y A. Hernansáez.-- Riesgos de los productos químicos potencialmente tóxicos, por Eugenio Laborda. Eduardo de la Peña y Elina Valcarece.-- Geografía. Otra crítica del neomalthusianismo, por María Isabel Bodega Fernández, Sici/ia Gutiérrez Ronco, María Asunción Martín Lou, Antonio Higueras Arnal y José Manuel Casas Torres.-- Notas.-- BibligrafíaPeer reviewe