The Global Retinoblastoma Outcome Study : a prospective, cluster-based analysis of 4064 patients from 149 countries

Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Illness and injury of travellers abroad : Finnish nationwide data from 2010 to 2012, with incidences in various regions of the world

The number of international tourist arrivals reached 1,000 million in 2012. Assessment of travellers' health problems has relied on proportionate morbidity data. Given the lack of data on number of visitors to each region, incidences have been impossible to calculate. This study, largest yet reporting travellers' health problems, is the first to present incidence of illness and injury. Data on Finnish travellers with health problems abroad during 2010 to 2012 were retrieved from the database of an assistance organisation, SOS International, covering 95% of those requiring aid abroad. The numbers were compared with those of Finnish travellers in the database of the Official Statistics of Finland. The SOS International database included 50,710 cases: infections constituted the most common health problem (60%), followed by injuries (14%), diseases of skin (5%), musculoskeletal system and connective tissue (5%), digestive tract (3%), and vascular system (2%). Gastroenteritis (23%) and respiratory infections (21%) proved the most frequent diagnoses. Overall incidence of illness or injury was high in Africa (97.9/100,000 travel days; 95% Bayesian credible interval (BCI): 53.1-145.5), southern Europe plus the eastern Mediterranean (92.3; 95% BCI: 75.4-110.1) and Asia (65.0; 95% BCI: 41.5-87.9). The data show significant differences between geographical regions, indicating the main risks and thus providing destination-specific tools for travellers' healthcare.Peer reviewe

Religion as a Cross-cultural Determinant of Depression in Elderly Europeans: Results from the EURODEP Collaboration

Background. The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans. Methods. Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17739). Results. In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries. Conclusions. Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life

Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma

Hypoxia and pH influence gene expression in tumours, and it is becoming increasingly clear that the pattern of genes expressed by a tumour determines its growth and survival characteristics. Hypoxia-inducible factor-1 (HIF-1) is a key mediator of the cellular response to hypoxia and high HIF-1 expression has been identified as a poor prognostic factor in tumours. Recently, we identified the tumour-associated carbonic anhydrases (CA), CA9 and CA12 as hypoxia-inducible in tumour cell lines. Furthermore, we identified CA IX to be a poor prognostic factor in breast cancer. The aim of this study was to assess the prognostic significance of CA XII. CA XII expression was studied by immunohistochemistry in a series of 103 cases of invasive breast cancer and any association with recognised prognostic factors or relation with the outcome was examined. CA XII expression was present in 77 out of 103 (75%) cases and was associated with lower grade (P=0.001), positive estrogen receptor status (P<0.001), and negative epidermal growth factor receptor status (P<0.001). Furthermore, although CA XII expression was associated with an absence of necrosis (P<0.001), expression of CA XII in some high-grade tumours was induced in regions directly adjacent to morphological necrosis. Additionally, using univariate analysis, CA XII positive tumours were associated with a lower relapse rate (P=0.04) and a better overall survival (P=0.01). In conclusion, CA XII expression is influenced both by factors related to differentiation and hypoxia in breast cancer in vivo and CA XII expression is associated with a better prognosis in an unselected series of invasive breast carcinoma patients

CAXII Is a Sero-Diagnostic Marker for Lung Cancer

To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer

Expression of a novel carbonic anhydrase, CA XIII, in normal and neoplastic colorectal mucosa

BACKGROUND: Carbonic anhydrase (CA) isozymes may have an important role in cancer development. Some isozymes control pH homeostasis in tumors that appears to modulate the behaviour of cancer cells. CA XIII is the newest member of the CA gene family. It is a cytosolic isozyme which is expressed in a number of normal tissues. The present study was designed to investigate CA XIII expression in prospectively collected colorectal tumor samples. METHODS: Both neoplastic and normal tissue specimens were obtained from the same patients. The analyses were performed using CA XIII-specific antibodies and an immunohistochemical staining method. For comparison, the tissue sections were immunostained for other cytosolic isozymes, CA I and II. RESULTS: The results indicated that the expression of CA XIII is down-regulated in tumor cells compared to the normal tissue. The lowest signal was detected in carcinoma samples. This pattern of expression was quite parallel for CA I and II. CONCLUSION: The down-regulation of cytosolic CA I, II and XIII in colorectal cancer may result from reduced levels of a common transcription factor or loss of closely linked CA1, CA2 and CA13 alleles on chromosome 8. Their possible role as tumor suppressors should be further evaluated

Alcohol use and health outcomes in the oldest old

BACKGROUND: As the United States population ages, an unprecedented proportion of the population will be aged 70 and older. Knowledge of alcohol use and its consequences in this age group is not well known. In light of the disparate findings pointing to negative outcomes with excessive drinking yet also benefits of moderate drinking, the true risk of alcohol use in late life needs more investigation. METHODS: This study examined the correlates and 2-year health outcomes related to alcohol use in 7,434 elders aged 70 years or older. Data was collected as part of the Assets and Health Dynamics of the Oldest Old (AHEAD), a nationwide health and economic study of elders. Data from Wave 1 and Wave 2 of AHEAD are presented. Frequency and quantity of drinking was assessed by self-report as was health status, lifetime alcohol or psychiatric problems, presence of chronic illness, functional impairment, and depressive symptoms. Cognitive status was assessed using a brief measure. RESULTS: Approximately 44% of the sample reported any alcohol use in the past three months, with the majority of drinking less than daily. Daily drinking was associated with being Caucasian, married, in relatively good health, and having good affective and cognitive status. Drinking was not associated with negative health outcomes two years later and was protective against stroke and functional impairment. Decline in drinking between Wave 1 and Wave 2 was strongly associated with poor health. CONCLUSION: This study offers no evidence of negative health outcomes for drinking moderately and confirms the U-shaped curve often found in studies of alcohol and health. Nonetheless, cessation of drinking was associated with poor health suggesting the health benefits of moderate drinking may result from selection of a healthy group of people capable of sustained moderate drinking. Public health recommendations for moderate drinking must take this phenomenon into account

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

Health status and lifestyle factors as predictors of depression in middle-aged and elderly Japanese adults: a seven-year follow-up of the Komo-Ise cohort study

<p>Abstract</p> <p>Background</p> <p>Depression is a common mental disorder. Several studies suggest that lifestyle and health status are associated with depression. However, only a few large-scale longitudinal studies have been conducted on this topic.</p> <p>Methods</p> <p>The subjects were middle-aged and elderly Japanese adults between the ages of 40 and 69 years. A total of 9,650 respondents completed questionnaires for the baseline survey and participated in the second wave of the survey, which was conducted 7 years later. We excluded those who complained of depressive symptoms in the baseline survey and analyzed data for the remaining 9,201 individuals. In the second-wave survey, the DSM-12D was used to determine depression. We examined the risks associated with health status and lifestyle factors in the baseline survey using a logistic regression model.</p> <p>Results</p> <p>An age-adjusted analysis showed an increased risk of depression in those who had poor perceived health and chronic diseases in both sexes. In men, those who were physically inactive also had an increased risk of depression. In women, the analysis also showed an increased risk of depression those with a BMI of 25 or more, in those sleeping 9 hours a day or more and who were current smokers. A multivariate analysis showed that increased risks of depression still existed in men who had chronic diseases and who were physically inactive, and in women who had poor perceived health and who had a BMI of 25 or more.</p> <p>Conclusions</p> <p>These results suggest that lifestyle and health status are risk factors for depression. Having a chronic disease and physical inactivity were distinctive risk factors for depression in men. On the other hand, poor perceived health and a BMI of 25 or more were distinctive risk factors for depression in women. Preventive measures for depression must therefore take gender into account.</p