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

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.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. Enucleation 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% (52·1-63·0) 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.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Implanted subcutaneous versus intraperitoneal bioscaffold seeded with hepatocyte-like cells: functional evaluation

Abstract Background and objectives The X-linked bleeding disorder, hemophilia A, is caused by defective production of factor VIII (FVIII). Hemophilic patients require regular FVIII infusions. Recombinant factor replacement poses the safest line of therapy. However, its main drawbacks are high expenses and the higher liability for formation of inhibitors. Recent studies confirmed the ability of bone marrow-derived stem cells to secrete FVIII. This study aims to generate bioscaffold from decellularized liver and subsequently seed it with trans-differentiated human stem cells into hepatic-like cells. This scaffold can then be implanted intraperitoneally or subcutaneously to provide FVIII. Methods After generation of the bioscaffold, seeding of discoid scaffolds with trans-differentiated human hepatocyte-like cells was performed. Then, the generated organoid was implanted into peritoneal cavity or subcutaneous tissue of experimental rats. Results Serum human FVIII was significantly increased in rats subjected to subcutaneous implantation compared intraperitoneal implantation. Immunostaining for detecting Cytokeratin 19 and human anti-globulin confirmed the presence of mature human hepatocytes that were significantly increased in subcutaneous implanted scaffold compared to the intraperitoneal one. Conclusion Implantation of decellularized bioscaffold seeded with trans-differentiated stem cells in rats was successful to establish production of FVIII. Subcutaneous implantation showed higher FVIII levels than intraperitoneal implantation. </jats:sec

The Efficacy of Antioxidant Oral Supplements on the Progression of COVID-19 in Non-Critically Ill Patients: A Randomized Controlled Trial

Modulation of cytokine production using immunonutrition is a relatively novel concept to improve outcomes among patients with SARS-CoV-2 infection and is now hypothesized to help manage COVID-19, however, clinical evidence is lacking. This prospective, double-blinded, randomized parallel-controlled interventional clinical trial investigated the effect of antioxidant supplements on inflammatory cytokines and disease progression in non-critically ill patients. A total of 87 hospitalized COVID-19 patients were randomized using computer-generated-randomization into the supplement group (n = 18) and the placebo group (n = 16) for 10 days. Baseline and final nutritional screening via nutrition risk screening (NRS-2002) and subjective global assessment (SGA), as well as the recording of anthropometric, clinical, biochemical, and functional parameters, were done. Serum ferritin level, cytokine storm parameters such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1(MCP-1), C-reactive protein, total leukocyte count, lymphocytic count, and neutrophil-to-lymphocyte ratio were measured. Anthropometric and clinical parameters showed nonsignificant differences between groups. The hematology profile showed improvement in lymphocyte count in the supplement group. However, levels of alkaline phosphatase, IL-6, TNF-α, and MCP-1 were significantly lower in the supplement group. In conclusion, antioxidant oral supplementation significantly reduced the cytokine storm and led to partial improvements in clinical parameters among patients with non-critical COVID-19.</jats:p

The Efficacy of Antioxidant Oral Supplements on the Progression of COVID-19 in Non-Critically Ill Patients: A Randomized Controlled Trial

Modulation of cytokine production using immunonutrition is a relatively novel concept to improve outcomes among patients with SARS-CoV-2 infection and is now hypothesized to help manage COVID-19, however, clinical evidence is lacking. This prospective, double-blinded, randomized parallel-controlled interventional clinical trial investigated the effect of antioxidant supplements on inflammatory cytokines and disease progression in non-critically ill patients. A total of 87 hospitalized COVID-19 patients were randomized using computer-generated-randomization into the supplement group (n = 18) and the placebo group (n = 16) for 10 days. Baseline and final nutritional screening via nutrition risk screening (NRS-2002) and subjective global assessment (SGA), as well as the recording of anthropometric, clinical, biochemical, and functional parameters, were done. Serum ferritin level, cytokine storm parameters such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1(MCP-1), C-reactive protein, total leukocyte count, lymphocytic count, and neutrophil-to-lymphocyte ratio were measured. Anthropometric and clinical parameters showed nonsignificant differences between groups. The hematology profile showed improvement in lymphocyte count in the supplement group. However, levels of alkaline phosphatase, IL-6, TNF-α, and MCP-1 were significantly lower in the supplement group. In conclusion, antioxidant oral supplementation significantly reduced the cytokine storm and led to partial improvements in clinical parameters among patients with non-critical COVID-19

Impact of Using Social Marketing Principles on Promoting Breastfeeding Practices and Physical Growth: an Egyptian Community Based Longitudinal Study

Abstract Background: Improving breastfeeding practices does not always link to interventions relying only on improving nutritional awareness and education but needs cultural and behavioral insights. Aim: Our study provided educational intervention through the use of the social marketing (SM) approach which was respectable to societal norms allowing more conscious choices by mothers to achieve the maximum potential of physical growth of their infants. This study evaluated the effectiveness of the used approach for improving breastfeeding practices and the physical growth of infants aged up to 2 years. Methods: A quasi-experimental intervention design with posttest-only control design was done along 3 years duration with 24 months of intervention and follow up for motivating mothers’ voluntary behavioral change towards breastfeeding promotion using SM principles: product, price, place, and promotion. The interventions targeted 646 pregnant women in their last trimester and mothers of children up to 2 years in addition to 1454 women in their childbearing period. Results: Most of the mothers showed increased awareness about the benefits of breastfeeding and became interested in breastfeeding their children outside the house using the breastfeeding cover (Gawn). Early breastfeeding initiation, exclusive breastfeeding (EBF) under 6 months, frequency of breastfeeding per day, percentage of infants who continued breastfeeding till 2 years, were significantly increased from 30%, 23 %, 56%, and 32% to 62 %, 47.3 %, 69 %, and 43.5 % respectively. With the attention of the nutritional educational sessions three or more times, the majority of indicators had the most significant improvement. The girls who recorded underweight results compared to boys, were significantly improved after the intervention (from 66.7 % to 18.8%). At the same time, girls that were found to be obese before the intervention (15.4 %) became no longer obese. Conclusions: Nutritional interventions that are based on the use SM approach showed improvement for the majority of the key performance indicators. Although they were doubled their value before the intervention yet the majority were still modest (below 50 %). With sustained use of the SM approach, infants will achieve their maximum potential for physical growth through providing economically disadvantaged mothers with breastfeeding support.</jats:p

Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries

Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countrie