Evidences for Paleo-Gas Hydrate Occurrence: What We Can Infer for the Miocene of the Northern Apennines (Italy)

The occurrence of seep-carbonates associated with shallow gas hydrates is increasingly documented in modern continental margins but in fossil sediments the recognition of gas hydrates is still challenging for the lack of unequivocal proxies. Here, we combined multiple field and geochemical indicators for paleo-gas hydrate occurrence based on present-day analogues to investigate fossil seeps located in the northern Apennines. We recognized clathrite-like structures such as thin-layered, spongy and vuggy textures and microbreccias. Non-gravitational cementation fabrics and pinch-out terminations in cavities within the seep-carbonate deposits are ascribed to irregularly oriented dissociation of gas hydrates. Additional evidences for paleo-gas hydrates are provided by the large dimensions of seep-carbonate masses and by the association with sedimentary instability in the host sediments. We report heavy oxygen isotopic values in the examined seep-carbonates up to +6h that are indicative of a contribution of isotopically heavier fluids released by gas hydrate decomposition. The calculation of the stability field of methane hydrates for the northern Apennine wedge-foredeep system during the Miocene indicated the potential occurrence of shallow gas hydrates in the upper few tens of meters of sedimentary column

Biochar Enhances Plant Growth, Fruit Yield, and Antioxidant Content of Cherry Tomato (Solanum lycopersicum L.) in a Soilless Substrate

Biochar soil amendment can improve growing medium water and nutrient status and crop productivity. A pot experiment was conducted using Solanum lycopersicum var. cerasiforme plants to investigate the effects of biochar amendment (20% application rate) on a soilless substrate, as well as on plant growth, fruit yield, and quality. During the experiment, substrate characteristics, plant morphological traits, and root and leaf C/N content were analyzed at three sampling points defined as early stage (36 days after germination), vegetative stage (84 days a. g.), and fruit stage (140 days a. g.). Fruit morphological traits, titratable acidity, lycopene, and solid soluble content were measured at the end of the experiment. Biochar ameliorated substrate characteristics (Nav increase of 17% and Ctot increase of 13% at the beginning of the study), resulting in a promotion effect on plant root, shoot, and leaf morphology mainly at the vegetative and fruit stages. Indeed, at these two sampling points, the biochar-treated plants had a greater number of leaves (38 and 68 at the vegetative and fruit stages, respectively) than the untreated plants (32 and 49, respectively). The biochar also increased leaf area with a rise of 26% and 36% compared with the values measured in the untreated plants. Moreover, the amendment increased twofold root length, root surface area, and root, stem, and leaf biomasses in comparison with untreated plants. Regarding plant productivity, although fruit morphology remained unchanged, biochar increased flower and fruit numbers (six times and two times, respectively), acidity (75%), lycopene (28%), and solid soluble content (16%). By unveiling promoting changes in morphological traits, fruit number, and antioxidant content occurring in cherry tomato plants growing in a biochar-treated soilless substrate, it could be possible to highlight the importance of biochar for future applications in the field for enhancing plant production and fruit quality in a sustainable agriculture framework

Strontium ranelate effect on bone mineral density is modified by previous bisphosphonate treatment

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and boneturnover markers after 1 year of treatment. Additionally, theeffect of SrR in bisphosphonate-naïve patients (BP-naïve)compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included482 postmenopausal women treated with SrR (2 g/day) for 1year in ten Argentine centers; 41 patients were excludeddue to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonatetreatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year oftreatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001),while the bone resorption marker s-CTX was decreased (p =0.0579). Also increases in BMD at the lumbar spine (LS,3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant(p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatmentwas higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ±0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatmentincreased BMD and bone formation markers and decreaseda bone resorption marker in the whole group, with betterresponse in BP-naïve patients.Fil: Brun, Lucas Ricardo Martín. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana M.. Hospital Italiano; ArgentinaFil: Vega, Eduardo. Instituto de la Mujer. Buenos Aires; ArgentinaFil: Salerni, Helena. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Maffei, Laura. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Premrou, Valeria. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Costanzo, Paulo R. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Sarli, Marcelo A. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Rey, Paula. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Larroudé, Maria S.. Hospital César Milstein; ArgentinaFil: Moggia, Maria S.. Centro Tiempo; ArgentinaFil: Brance, María Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; ArgentinaFil: Sánchez, Ariel. Centro de Endocrinología; ArgentinaFil: Grupo Argentino de Estudio del Ranelato de Estroncio. No especifica

Plasma p-Cresol Lowering Effect of Sevelamer in Peritoneal Dialysis Patients: Evidence from a Cross-Sectional Observational Study.

p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate, that represents more than 95% of circulating p-cresol, causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies able to reduce plasma p-cresol levels are highly demanded but unfortunately not available yet. Because it has been reported that the phosphate binder sevelamer also sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis patients, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. When we compared total p-cresol plasma concentrations in these different groups of patients, we, we found that plasma p-cresol levels were significantly lower in patients receiving sevelamer than in subjects receiving lanthanum or no drug. Patients assuming sevelamer had also lower high sensitivity C-reactive protein serum concentrations compared to patients not assuming this drug. Multiple linear regression analysis showed that Conversely, no difference either in residual glomerular filtration rate, total weekly dialysis dose or serum phosphate levels were observed among the different groups. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect the cardiovascular risk because of its anti-inflammatory effect

Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

&lt;p&gt;Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.&lt;/p&gt; &lt;p&gt;Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.&lt;/p&gt; &lt;p&gt;Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.&lt;/p&gt

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

Circadian analysis of myocardial infarction incidence in an Argentine and Uruguayan population

BACKGROUND: The occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay. METHODS: A cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals. RESULTS: A minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima. CONCLUSION: The results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population

Densitometric Response in Postmenopausal Osteoporosis Treated with Strontium Ranelate or Denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR.Facultad de Ciencias Médica

Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified asresponders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responnders was higher with Dmab than with SrR.Fil: Sánchez, Ariel. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología SRL; ArgentinaFil: Brun, Lucas Ricardo Martín. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Salerni, Helena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Costanzo Caso, Pablo Alejandro. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Maffei, Ana Laura. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Pemrou, Valeria. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Sarli, Marcelo A.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Rey, Paula. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Larraoudé, María Silvia. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Hospital Milstein; ArgentinaFil: Brance, María Lorena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana María. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Servicio de Endocrinología del Hospital Italiano de Buenos Aires; ArgentinaFil: Gonzalez, Diana. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Bagur, Alicia Cristina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Vega, Eduardo. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Cesan; Argentina. Instituto de la Mujer; ArgentinaFil: Zanchetta, María B.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Farias, Vanina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Manzur, José L.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteoporosis; ArgentinaFil: Moggia, María S.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro Tiempo; ArgentinaFil: Ulla, María R.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteopatías Médicas; ArgentinaFil: Pavlove, María M.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Carlos Durand.; ArgentinaFil: Karlsbrum, Silvia. Hospital Durand; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Grupo Argentino de Estudio de la Osteoporosis. No especifíca

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