Highlights d Unsupervised clustering revealed subtype with EMT and phosphoprotein signatures d Potential therapeutic vulnerabilities included survivin, NSD3, LSD1, and EZH2 d Rb phosphorylation nominated as a biomarker for trials with CDK4/6 inhibitors d Detailed immune landscape analysis highlighted targetable points of immuneregulation

Presence of axial involvement was associated with a higher likelihood of moderate/severe psoriasis, with higher disease activity and greater effect on quality of life. These findings highlight the importance of monitoring patients with PsA for signs of axial symptoms or spinal involvement.

Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated.

Background and Purpose-Argatroban is a direct thrombin inhibitor that safely augments recanalization achieved by tissue-type plasminogen activator (tPA) in animal stroke models. The Argatroban tPA Stroke Study was an open-label, pilot safety study of tPA plus Argatroban in patients with ischemic stroke due to proximal intracranial occlusion. Methods-During standard-dose intravenous tPA, a 100-g/kg bolus of Argatroban and infusion for 48 hours was adjusted to a target partial thromboplastin time of 1.75ϫ baseline. The primary outcome was incidence of significant intracerebral hemorrhage defined as either symptomatic intracerebral hemorrhage or Parenchymal Hematoma Type 2. Recanalization was measured at 2 and 24 hours by transcranial Doppler or CT angiography. Results-Sixty-five patients were enrolled (45% men, mean age 63Ϯ14 years, median National Institutes of Health Stroke Scaleϭ13). The median (interquartile range) time tPA to Argatroban bolus was 51 (38 -60) minutes. Target anticoagulation was reached at a median (interquartile range) of 3 (2-7) hours. Significant intracerebral hemorrhage occurred in 4 patients (6.2%; 95% CI, 1.7-15.0). Of these, 3 were symptomatic (4.6%; 95% CI, 0.9 -12.9). Seven patients (10%) died in the first 7 days. Within the 2-hour monitoring period, transcranial Doppler recanalization (nϭ47) occurred in 29 (61%) patients: complete in 19 (40%) and partial in another 10 (21%). Conclusions-The combination of Argatroban and intravenous tPA is potentially safe in patients with moderate neurological deficits due to proximal intracranial arterial occlusions and may produce more complete recanalization than tPA alone. T he thrombin inhibitor Argatroban (GlaxoSmithKline, Philadelphia, PA) selectively inhibits free and clotassociated thrombin. 1,2 Safety has been demonstrated with and without thrombolytics or with aspirin in patients with acute myocardial infarction. [3][4][5] In a randomized trial of Argatroban versus heparin in combination with intravenous thrombolysis for acute myocardial infarction, complete coronary reperfusion was significantly more frequent with Argatroban compared with heparin. 3 In animal stroke models, Argatroban safely augments the benefit of recombinant tissue-type plasminogen activator (tPA) by improving microcirculatory flow, increasing speed and completeness of recanalization, and preventing reocclusion. 6 -10 Argatroban monotherapy (in a double-blind, randomized Phase II trial) in 60 patients with stroke within 48 hours of onset improved The benefit of tPA in acute stroke is linked to the speed and degree of clot lysis and artery recanalization. 16 -18 However, only 20% to 30% of patients will have complete recanalization on transcranial Doppler imaging (TCD) within 2 hours of intravenous tPA therapy, 60% will have only partial recanalization, and 34% of those with any recanalization will experience reocclusion. 19,20 Because of its short half-life, allowing careful titration of the anticoagulant effect, we hypothesized that Argatroban might be safely added to...

Background and Purpose-The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods-ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke