OUTCOMES OF OVERT AND NON-OVERT DISSEMINATED INTRAVASCULAR COAGULATION USING THE ISTH DIC SCORING SYSTEM IN CHILDREN: A SINGLE-CENTER STUDY

Background: Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. This study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system. Methods: This retrospective study reviewed data on children aged 1 month to 15 years diagnosed with DIC between 2003 and 2014. Results: Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs 15.6%; P < 0.001). DIC scores were significantly associated with mortality (R2 = 0.89). Each clinical parameter (platelet count, prothrombin time, and fibrin degradation products) was associated with mortality (P = 0.01). On multivariable analysis, the factors associated with death were platelet counts ≤ 50 000 cells/mm3 (OR, 2.42; 95% CI, 1.08–5.42; P = 0.031); overt DIC score (OR, 7.62; 95% CI, 2.94–19.75; P < 0.001); renal dysfunction (OR, 2.92; 95% CI, 1.34–6.37; P = 0.007); shock (OR, 39.62; 95% CI, 4.99–314.84; P = 0.001); and acute respiratory distress syndrome (OR, 25.90; 95% CI, 3.12–214.80; P = 0.003). Conclusions: The 28-day case-fatality rate was significantly higher for patients with overt than non-overt DIC and concordant with ISTH scores. ISTH DIC scores can be used as a clinical predictor for DIC in children

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

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

Mediastinal Germinoma Associated with Hemophagocytic Lymphohistiocytosis: A Case Report

Background: Malignancy-associated hemophagocytic syndrome (MAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), can be found with several types of malignancy. It can be manifested either before or after the diagnosis of the underlying malignancy. However, mediastinal germinoma associated HLH has never been reported in previous literatures. Case report: A 13-year-old boy presented with prolonged fever for 10 days with marked hepatosplenomegaly and progressive bicytopenia. Additional investigations demonstrated hyperferritinemia and increased hemophagocytic activity in the bone marrow without evidence of malignancy, compatible with the diagnosis of HLH. He responded well to the HLH-treatment with intravenous immunoglobulins and dexamethasone, but the HLH recrudesced 5 days later. Further investigation revealed anterior mediastinal mass. He quickly deteriorated afterwards and developed pulmonary hemorrhage leading to respiratory failure and died on the following day. Result of the post-mortem tumor biopsy was consistent with mediastinal germinoma. Conclusion: MAHS should be considered in HLH patients who do not respond well or develop recurrence after the appropriate HLH-immunochemotherapy. HLH associated with mediastinal germinoma is rare and fatal. Making diagnosis of the underlying mediastinal germinoma is complicated and challenging. Early diagnosis and prompt treatment of HLH along with the appropriate treatment of germinoma might be the important key for the treatment success

Treatment Outcomes of Kasabach-Merritt Syndrome: A Single Hospital Experience

Objective: Although the outcomes of treatment of Kasabach-Merritt syndrome (KMS) have improved over time, some patients succumb to uncontrollable hemorrhage. Additionally, there is no consensus guideline for the management of KMS. Clinical research on KMS might benefit physicians who treat such patients. Methods: A retrospective chart review of patients diagnosed as KMS by Siriraj Hospital from 2006 to 2016 was conducted. Results: Ten patients were diagnosed with KMS. Four patients underwent surgical intervention and obtained pathological results; 3 of them had kaposiform hemangioendothelioma (KHE), while the fourth had infantile hemangioma (IH). The combination of propranolol and prednisolone, with or without vincristine, was the most common first-line regimen, with a complete response of 37.5%. A combination of vincristine, aspirin, and ticlopidine (VAT) was prescribed as the second-line therapy for 5 patients, but there were no responses in this cohort. Another 2 patients attained hematological remission with embolization and prednisolone monotherapy. A further 2 patients with KHE who were refractory to other treatments responded well to sirolimus, while the tenth patient died of abdominal hemorrhage. Conclusion: The combination of propranolol and prednisolone seems to be effective for KMS. Sirolimus may be considered for salvage therapy for those whose disease is recalcitrant to standard treatment, especially in cases of KMS secondary to KHE. However, research on a larger cohort should be conducted to substantiate the efficacy of such treatments

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.Y