SummaryTreatment with heparin or streptokinase was allocated randomly to 30 patients with life-threatening pulmonary embol'sm verified by angiography. Treatment was given for 72 hours and pulmonary angiography was repeated. There was significantly greater (P <0001) evidence of thrombolysis in those patients treated with streptokinase compared with those treated with heparin. The reduction of systolic and mean pulmonary arterial pressures was also significantly greater (P < 0 05 and P < 0-02 respectively) in the streptokinase group.Seven patients failed to complete 72 hours of the trial treatment: five successfully underwent pulmonary embolectomy. Six of these "failures" had initial pulmonary angiographic scores of 24 or more and systemic systolic blood pressure recordings of 100 mm Hg or less. Patients with these features should probably be considered for pulmonary embolectomy as the initial treatment.

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Key Points ASXL1/EZH2, transfusion dependence, and a high prognostic risk score predict shorter TTF in MF patients on JAK1/2 inhibitors. These clinical and genetic factors were also associated with decreased overall survival.

Context.-Detection of variants in hematologic malignancies is increasingly important because of a growing number of variants impacting diagnosis, prognosis, and treatment response, and as potential therapeutic targets. The use of next-generation sequencing technologies to detect variants in hematologic malignancies in a clinical diagnostic laboratory setting allows for efficient identification of routinely tested markers in multiple genes simultaneously, as well as the identification of novel and rare variants in other clinically relevant genes.Objective.-To apply a systematic approach to evaluate and validate a commercially available next-generation sequencing panel (TruSight Myeloid Sequencing Panel, Illumina, San Diego, California) targeting 54 genes. In this manuscript, we focused on the parameters that were used to evaluate assay performance characteristics.Data Sources.-Analytical validation was performed using samples containing known variants that had been identified previously. Cases were selected from different disease types, with variants in a range of genes. Panel performance characteristics were assessed and genomic regions requiring additional analysis or wet-bench approaches identified.Conclusions.-We validated the performance characteristics of a myeloid next-generation sequencing panel for detection of variants. The TruSight Myeloid Sequencing Panel covers more than 95% of target regions with depth greater than 5003. However, because of unique variant types such as large insertions or deletions or genomic regions of high GC content, variants in CEBPA, FLT3, and CALR required supplementation with non-next-generation sequencing assays or with informatics approaches to address deficiencies in performance. The use of multiple bioinformatics approaches (2 variant callers and informatics scripts) allows for maximizing calling of true positives, while identifying limitations in using either method alone.

A common approach in clinical diagnostic laboratories to variant assessment from tumor molecular profiling is sequencing of genomic DNA extracted from both tumor (somatic) and normal (germline) tissue, with subsequent variant comparison to identify true somatic variants with potential impact on patient treatment or prognosis. However, challenges exist in paired tumor-normal testing, including increased cost of dual sample testing and identification of germline cancer predisposing variants. Alternatively, somatic variants can be identified by in silico tumor-only variant filtration precluding the need for matched normal testing. The barrier to tumor-only variant filtration is defining a reliable approach, with high sensitivity and specificity to identify somatic variants. In this study, we used retrospective data sets from paired tumor-normal samples tested on small (48 gene) and large (555 gene) targeted next-generation sequencing panels, to model algorithms for tumor-only variants classification. The optimal algorithm required an ordinal filtering approach using information from variant population databases (1000 Genomes Phase 3, ESP6500, ExAC), clinical mutation databases (ClinVar), and information on recurring clinically relevant somatic variants. Overall the tumor-only variant filtration strategy described in this study can define clinically relevant somatic variants from tumor-only analysis with sensitivity of 97% to 99% and specificity of 87% to 94%, and with significant potential utility for clinical laboratories implementing tumor-only molecular profiling. (J Mol Diagn 2019, 21: 261e273; https://doi.

Critical incidents occur frequently in EDs. There are significant differences, as well as common themes, in the causes of these critical incidents between different EDs.