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

Trends in incidence of malignant melanoma in the elderly (aged 65+ years) in England, 1971–2010

Background: Malignant melanoma is the 5th most common cancer in the UK. Over the past four decades, incidence rates of malignant melanoma have increased more than for any other common cancer. The highest incidence rates are observed in the elderly aged 65+ years [accounting for about half (49%) of all cases]. Aim: To determine trends in incidence of malignant melanoma in the elderly in England during the period 1971–2010. Methods: Population-based national cancer registration data were analysed to determine the incidence of malignant melanoma (ICD-9: 172; ICD-10: C43) by age (65–69, 70–74, 75–79, 80–84, and 85+), gender, morphological sub-type and anatomical site of tumour. Results: During the 40-year period, a total of 69,496 cases of malignant melanoma among the elderly aged 65+ years were registered in England (44.7% males, 55.3% females). The total number of cases increased from 2,023 in 1971-75 (405 cases/year) to 21,132 in 2006-10 (4,226 cases/year). The incidence rate (per 100,000) increased from 5.1 in 1971-75 to 61.4 in 2006-10 in males (12-fold increase); and from 7.0 to 42.6 in females (6-fold increase). The majority of cases (95.3%) were diagnosed by histology. The most common morphological sub-type was superficial spreading melanoma (24.5%); and in 2006-10, the most common anatomical site was ‘trunk’ (35.2%) in males and ‘lower limb’ (38.8%) in females. During the study period, the largest increase in incidence rate, according to anatomical site, was observed for ‘trunk’ (534-fold) in males and ‘lower limb’ (17-fold) in females. Conclusions: During the past four decades, there has been a remarkable increase in the incidence of malignant melanoma among the elderly in England. The largest increase was observed in the malignant melanoma involving the ‘trunk’ in males. Considering that an estimated 86% of malignant melanoma cases in the UK are linked to the ultraviolet radiation from the sun, effective lifestyle and behaviour change education could have an enormous impact on primary prevention and reducing the incidence of the disease. The findings are also relevant for the organisation and commissioning of oncology services and resource allocation

Current management of moderate to severe traumatic pneumothoraces: A survey of emergency clinicians

Background: Traumatic pneumothoraces are present in one-fifth of multiple trauma victims. Traditional teaching mandates the insertion of a chest drain in the majority of cases. However, recent observational evidence suggests a trend towards conservative management. The aim of this survey was to understand current emergency medicine (EM) practice in placing chest drains for the management of moderate to severe traumatic pneumothoraces. Methodology: The survey was developed through expert consensus and sent electronically to senior EM doctors in 21 sites internationally. It described six clinical/imaging vignettes asking how likely are you to insert an intercostal chest drain to manage the pneumothorax in ED?'. A five-point response was available from very unlikely to very likely. All pneumothoraces were >1 cm on imaging, but mechanism, physiology and need for ventilation varied. Results: Of a potential 606 respondents, 222 responses were received (37% response rate). Respondents were from five different countries, with the majority qualified for more than 10 years (median; 18 years). Within each scenario, there was a large variation in responses with the exception of tension pneumothorax. For vignettes without tension pneumothorax, there was a range from 52% (non-compromised 1 cm pneumothorax in a ventilated patient) to 89% (open pneumothorax with minimal clinical compromise) in respondents reporting that they would be likely or very likely to insert a chest drain. Conclusion: There is considerable variation in clinical practice involving both conservative and invasive strategies in the treatment of moderate to severe traumatic pneumothoraces. This suggests clinical equipoise for interventional trials to determine the optimal management strategy for this patient group

Gut microbiota and aging-A focus on centenarians

Gut microbiota (GM) is a dynamic organ throughout the lifespan. Aging is a complex process that comprises a plethora of mechanisms such as senescence, immunosenescence and inflammaging, representing important pathways of age-related diseases. GM structure could both influence and be influenced by aging occurring changes within the host. A unique category of long living individuals exists, namely centenarians that have the outstanding capacity to adapt to various challenges. Longevity seems to be associated with certain GM which, among other factors, might render individuals more resistant to age-related diseases and subsequently to long living. Diet, prebiotics, probiotics and synbiotics may contribute to longevity through GM modulating. Currently, the exact mechanisms of the association between GM and the host in relation with extended lifespan remain unknown and should be further investigated