Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500–24000] versus VV 28,800 IU [IQR 17,300–40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

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ObjectiveHyperaggressive resection refers to a philosophy that maximal resection should be pursued in gliomas, wherever possible. In this study, we provide a detailed report of the outcomes with hyperaggressive surgery for multilobar insular-involving gliomas (MIGs). MethodsWe report outcomes in patients with MIGs undergoing surgery aiming at gross total resection in all cases. Risk factors for neurologic deficits and survival were modeled using logistic and Cox regression.ResultsThere were 72 consecutive patients, of whom 53 (74%) had undergone previous surgery. A greater than 90% resection was obtained in 67 patients (93%). Nineteen of 23 patients (83%) with Grade 2 tumors survived to the end of the follow-up period. Patients with Grade 3 tumors experienced 75% two-year survival rates and 48% four-year survival rates. Patients with Grade 4 tumors experienced 55% one-year survival rates and 33% two-year survival rates; eight of 33 patients (24%) lived longer than three years and three of 33 patients were alive at five years. Fifty-eight of 68 patients (85%) surviving to the three-month follow-up had a Karnofsky performance status (KPS) of 70 or greater, and 31 of 72 patients (43%) experienced improvement in KPS postoperatively. Permanent weakness occurred in 12 patients (17%), and permanent speech problems in three patients (13% of left-sided tumors).ConclusionHyperaggressive surgical resection of MIGs yields rates of neurologic deficits within acceptable ranges and are lower than expected. In many cases, patients exceed the long-term survival expectations of conventional treatment.

NPM1-mutated AML represents a WHO leukemia entity with unique pathological and clinical features. Little is known about the characteristics of "therapy-related" NPM1-mutated AML. We compared the genetics, transcriptional profile and clinical outcome of therapy-related NPM1-mutated AML (t-NPM1 AML), de-novo NPM1-mutated AML (dn-NPM1 AML) and therapy-related AML with wild-type NPM1 (t-AML). A normal karyotype was more frequent in t-NPM1 AML (n=78/96 cases, 88%) and dn-NPM1 (n=1986/2394,88%) than in t-AML (n=103/390,28%; p &lt;0.001). DNMT3A and TET2 were mutated in 43% and 40% of t-NPM1 AML (n=107), similar to dn-NPM1 (n=88, 48% and 30%; p-values &gt;0.1), but more frequently than t-AML (n=162; 14% and 10%; p-values &lt;0.001). TP53 and PPM1D, typically mutated in t-AML, were consistently wild-type in t-NPM1 AML (97% and 96%). t-NPM1 and dn-NPM1 AML were transcriptionally similar, displaying upregulation of HOX genes and down-regulation of CD133 and CD34. With a median follow-up of 62 months, 3-year overall survival (OS) for t-NPM1 AML (n=96), dn-NPM1 AML (n=2394) and t-AML (n=390) was 54%, 60% and 31%. In multivariable analysis OS was similar for the two NPM1-mutated groups (HR 0.9, 95%CI 0.65-1.25, p=0.45) but better in t-NPM1 AML than t-AML (HR 1.86, 95%CI 1.30-2.68, p&lt;0.001). Relapse-free survival did not differ between t-NPM1 and dn-NPM1 AML (HR 1.02, 95%CI 0.72-1.467, p=0.90) but was significantly higher in t-NPM1 AML than t-AML (HR 1.77, 95%CI 1.19-2.64, p=0.0045).t-NPM1 and dn-NPM1 AML have similar clinical, genomic and transcriptomic features, suggesting that they should be classified as a single disease entity