Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry.

BACKGROUND: Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. METHODS: Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. RESULTS: Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. CONCLUSIONS: Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Highlights of Children with Cancer UK's Workshop on Drug Delivery in Paediatric Brain Tumours.

The first Workshop on Drug Delivery in Paediatric Brain Tumours was hosted in London by the charity Children with Cancer UK. The goals of the workshop were to break down the barriers to treating central nervous system (CNS) tumours in children, leading to new collaborations and further innovations in this under-represented and emotive field. These barriers include the physical delivery challenges presented by the blood-brain barrier, the underpinning reasons for the intractability of CNS cancers, and the practical difficulties of delivering cancer treatment to the brains of children. Novel techniques for overcoming these problems were discussed, new models brought forth, and experiences compared.

A study to assess management of patients on warfarin by general dental practitioners (GDPs) in the West Midlands.

UNLABELLED: Current management protocols for anticoagulated patients undergoing dental procedures are influenced by evidence-based guidelines. These guidelines state that the risk of significant bleeding is low in patients who have a stable INR within a therapeutic range, (2-4). The risks of interruption of anticoagulant therapy is greater than the risk of bleeding. This paper discusses the current practice of general dental practitioners (GDPs) in the West Midlands when treating patients taking warfarin and compares these findings with standard guidelines. A questionnaire was sent to 638 GDPs in West Midlands in 2010, 492 (77%) were returned. This study was carried out three years after a similar study carried out in South West Wales and after the guidance updated by the BNF and NMWIC. Thirty-three (7%) of the respondents did not treat patients on warfarin. The majority of respondents (86%) considered that a dental extraction in a patient on warfarin is a procedure associated with a high risk of bleeding. Surgical implant placement (75%), subgingival debridement (49%) and inferior dental block (40%) administration were also considered by GDPs to be associated with a high risk of bleeding.The majority (88%) of the respondents check the INR of anticoagulated patients before carrying out treatment. Of these, 244 (52%) would do so within 24 hours and 78 (17%) of them within 72 hours. Only 117 (25%) considered 4.0 as the safe upper limit for the INR for performing high-risk procedures. CLINICAL RELEVANCE: The findings of this study demonstrate that there is general awareness about how to manage patients on warfarin but uncertainties still exist among general dental practitioners. Further education and training would improve the care of patients on warfarin in a primary care setting.

Venous thromboembolic disease in trauma and surveillance ultrasonography.

BACKGROUND: The literature reports a wide variation in the incidence of venous thromboembolic (VTE) disease in trauma patients. The performance of routine surveillance venous duplex ultrasound of bilateral lower extremities is controversial. Furthermore, recent examinations of the national trauma databank registry have suggested that routine duplex surveillance is associated with higher deep venous thrombosis (DVT) detection rates. MATERIALS AND METHODS: We examined the incidence and risk factors for VTE disease in 2827 trauma patients admitted over a 2-y period to a state-verified level I trauma center. Detailed chart review was carried out for patients with VTE disease. We then evaluated the effects of a routine bilateral lower extremity duplex surveillance guideline on VTE detection in the subset of injury patients admitted to the trauma service. RESULTS: We found an approximately 2% incidence of venous thromboembolic disease in a mostly blunt trauma population. Amongst patients with VTE disease, the most common risk factors were obesity and significant head injury. We then evaluated the 998 patients with injury who were admitted to the trauma service 1 y before and after surveillance guideline implementation. Despite a nearly 5-fold increase in the number of duplex scans, with a substantial increase in cost, we found no significant difference in the incidence of DVT. CONCLUSIONS: Our preliminary data argue against the use of routine duplex surveillance of lower extremities for DVT in trauma patients. A larger, prospective analysis is necessary to confirm these findings.

Mixing during intravertebral arterial infusions in an in vitro model.

Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments.