Updates on accelerated and blast phase myeloproliferative neoplasms: Are we making progress?

Management approaches for accelerated and blast phase myeloproliferative neoplasms remain challenging for clinicians and patients alike. Despite many therapeutic advances, outcomes for those patients who are not allogeneic haematopoietic cell transplant eligible remain, in general, very poor. Estimated survival rates for such blast phase patients is frequently reported as less than 6 months. No specific immunological, genomic or clinicopathological signature currently exists that accurately predicts the risk and timing of transformation, which frequently induces a high degree of anxiety among patients and clinicians alike. Within this review article, we provide an up-to-date summary of current understanding of the underlying pathogenesis of accelerated and blast phase disease and discuss current therapeutic approaches and realistic outcomes. Finally, we discuss how the horizon may look with the introduction of more novel agents into the clinical arena.

Cerebral MRI findings predict the risk of cognitive impairment in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombomicroangiopathy caused by deficiency of ADAMTS13. Acute neurological involvement is well described, but its long-term impact requires evaluation. One-hundred thirty-one patients, following an acute TTP event, with severe headache or neurological symptoms had a cerebral MRI. Fifty-six percent had abnormal imaging, more commonly in patients with neurological symptoms than headaches only (80% vs. 18%, P < 0·0001). In remission, 27% (n = 35) reported persistent cognitive symptoms: specifically, impaired memory (66%), difficulty concentrating (26%), and word-finding difficulties not secondary to an acute stroke (26%). Sixty-five percent also reported depression and 55% reported anxiety, regardless of presenting neurology. The frontal lobe was disproportionally affected in patients with marked intellectual impairment, seen in 67% of patients compared to 19% of patients without intellectual impairment (P = 0·002). The primary MRI finding in these patients was hyperintense white matter lesions. An abnormal MRI was associated with a lower median verbal IQ (85 vs. 99, P = 0·02) and performance IQ (83 vs. 100, P = 0·02). In conclusion, neurological symptoms are frequently associated with an abnormal cerebral MRI scan, and white matter frontal lobe lesions are particularly significant, leading to marked intellectual impairment. Anxiety and depression were evident in over half of patients, regardless of neurological involvement at presentation.

Improving ultrasound video classification: an evaluation of novel deep learning methods in echocardiography.

Echocardiography is the commonest medical ultrasound examination, but automated interpretation is challenging and hinges on correct recognition of the 'view' (imaging plane and orientation). Current state-of-the-art methods for identifying the view computationally involve 2-dimensional convolutional neural networks (CNNs), but these merely classify individual frames of a video in isolation, and ignore information describing the movement of structures throughout the cardiac cycle. Here we explore the efficacy of novel CNN architectures, including time-distributed networks and two-stream networks, which are inspired by advances in human action recognition. We demonstrate that these new architectures more than halve the error rate of traditional CNNs from 8.1% to 3.9%. These advances in accuracy may be due to these networks' ability to track the movement of specific structures such as heart valves throughout the cardiac cycle. Finally, we show the accuracies of these new state-of-the-art networks are approaching expert agreement (3.6% discordance), with a similar pattern of discordance between views.

Effects of Percutaneous Coronary Intervention on Death and Myocardial Infarction Stratified by Stable and Unstable Coronary Artery Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In patients presenting with ST-segment-elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post-myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment-elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non-ST-segment-elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials. METHODS AND RESULTS: We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45-1.03); P=0.07; multivessel disease following ST-segment-elevation myocardial infarction (RR, 0.84 [95% CI, 0.69-1.04]; P=0.11); non-ST-segment-elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72-0.97]; P=0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75-0.93]; P=0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53-0.90]; P=0.007) and MI (RR, 0.74 [95% CI, 0.62-0.90]; P=0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87-1.11]), cardiac death (RR, 0.89 [95% CI, 0.71-1.12]; P=0.33), or MI (RR, 0.96 [95% CI, 0.86-1.08]; P=0.54). CONCLUSIONS: PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.