Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Disposable Platform Provides Visual and Color-Based Point-of-Care Anemia Self-Testing

Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels. METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying degrees and etiologies and compared hematology analyzer Hgb levels with POC Hgb levels, which were estimated via visual interpretation using a color scale and an optional smartphone app for automated analysis. RESULTS. POC Hgb levels correlated with hematology analyzer Hgb levels (r = 0.864 and r = 0.856 for visual interpretation and smartphone app, respectively), and both POC test methods yielded comparable sensitivity and specificity for detecting any anemia (n = 178) (/dl) (sensitivity: 90.2% and 91.1%, specificity: 83.7% and 79.2%, respectively) and severe anemia (n = 10) (/dl) (sensitivity: 90.0% and 100%, specificity: 94.6% and 93.9%, respectively). CONCLUSIONS. These results demonstrate the feasibility of this POC color-based diagnostic test for self-screening/self-monitoring of anemia. TRIAL REGISTRATION. Not applicable. FUNDING. This work was funded by the FDA-funded Atlantic Pediatric Device Consortium, the Georgia Research Alliance, Children\u27s Healthcare of Atlanta, the Georgia Center of Innovation for Manufacturing, and the InVenture Prize and Ideas to Serve competitions at the Georgia Institute of Technology

Direct oral anticoagulants in patients with venous thromboembolism and thrombophilia: a systematic review and meta-analysis

Essentials We investigated direct oral anticoagulant (DOAC) use in venous thromboembolism and thrombophilia. A comprehensive search identified 10 studies, 8 of which were included in a meta-analysis. DOACs were overall safe and effective in patients with venous thromboembolism and thrombophilia. Efficacy/safety of DOACs was maintained in low-risk antiphospholipid syndrome patient subgroup. Summary: Background Direct oral anticoagulants (DOACs) are increasingly used in acute and long-term treatment of venous thromboembolism (VTE). However, their role in management of thrombophilia-associated VTE is controversial. Methods Through a comprehensive search on MEDLINE, Cochrane Library, and Clinicaltrials.gov, we identified 10 eligible studies, 8 of which reporting data on 1994 thrombophilia patients were included in a random-effects meta-analysis. Eligible studies were phase 2 to 3 randomized controlled trials comparing DOACs to vitamin K antagonists (VKAs) in patients with VTE, including those with thrombophilia. Results Of eight studies included in meta-analysis, four evaluated rivaroxaban, three dabigatran, and one edoxaban. No results could be obtained on apixaban use. The rates of VTE recurrence (RR, 0.70; 95% CI, 0.34–1.44; I 2  = 0%) and major/clinically relevant non-major bleeding events (RR, 0.92; 95% CI, 0.62–1.36; I 2  = 23%) were similar between thrombophilia patients treated with DOACs compared to VKAs. Results were comparable to findings in patients without known thrombophilia: RR, 1.02; 95% CI, 0.80–1.30; I 2  = 46% for VTE recurrence and RR, 0.72; 95% CI, 0.57–0.90; I 2  = 84% for major/clinically relevant non-major bleeding events. Conclusions Rates of VTE recurrence and bleeding events were both low and comparable in patients with various thrombophilias receiving either treatment, suggesting that DOACs are an appropriate treatment option in this population. Due to limited data, it is unclear whether these findings apply to specific subgroups such as high-risk antiphospholipid syndrome, uncommon thrombophilias, or the use of apixaban