Bleeding Severity in Percutaneous Coronary Intervention (PCI) and Its Impact on Short-Term Clinical Outcomes

Bleeding severity in patients undergoing percutaneous coronary intervention (PCI), defined by the Bleeding Academic Research Consortium (BARC), portends adverse prognosis. We analysed data from 37,866 Australian patients undergoing PCI enrolled in the Victorian Cardiac Outcomes Registry (VCOR), and investigated the association between increasing BARC severity and in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) (a composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, or stroke). Independent predictors associated with major bleeding (BARC groups 3&5), and MACCE were also assessed. There was a stepwise increase in in-hospital and 30-day MACCE with greater severity of bleeding. Independent predictors of bleeding included female sex (Odds Ratio (OR) 1.34), age (OR 1.02), fibrinolytic therapy (OR 1.77), femoral access (OR 1.51), and ticagrelor (OR 1.42), all significant at the p < 0.001 level. Following adjustment of clinically important variables, BARC 3&5 bleeds (OR 4.37) were still predictive of cumulative in-hospital and 30-day MACCE. In conclusion, major bleeding is an uncommon but potentially fatal PCI complication and was independently associated with greater MACCE rates. Efforts to mitigate the occurrence of bleeding, including radial access and judicious use of potent antiplatelet therapies, may ameliorate the risk of short-term adverse clinical outcomes

Brain Tumor Segmentation from Multi-Spectral MR Image Data Using Random Forest Classifier

The development of brain tumor segmentation techniques based on multi-spectral MR image data has relevant impact on the clinical practice via better diagnosis, radiotherapy planning and follow-up studies. This task is also very challenging due to the great variety of tumor appearances, the presence of several noise effects, and the differences in scanner sensitivity. This paper proposes an automatic procedure trained to distinguish gliomas from normal brain tissues in multi-spectral MRI data. The procedure is based on a random forest (RF) classifier, which uses 80 computed features beside the four observed ones, including morphological ones, gradients, and Gabor wavelet features. The intermediary segmentation outcome provided by the RF is fed to a twofold post-processing, which regularizes the shape of detected tumors and enhances the segmentation accuracy. The performance of the procedure was evaluated using the 274 records of the BraTS 2015 train data set. The achieved overall Dice scores between 85-86% represent highly accurate segmentation

Differences in outcomes of patients with in-hospital versus out-of-hospital ST-elevation myocardial infarction: a registry analysis

OBJECTIVES Patients with ST-elevation myocardial infarction (STEMI) that occur while already in hospital ('in-hospital STEMI') face high mortality. However, data about this patient population are scarce. We sought to investigate differences in reperfusion and outcomes of in-hospital versus out-of-hospital STEMI. DESIGN, SETTING AND PARTICIPANTS Consecutive patients with STEMI all treated with percutaneous coronary intervention (PCI) across 30 centres were prospectively recruited into the Victorian Cardiac Outcomes Registry (2013-2018). PRIMARY AND SECONDARY OUTCOMES Patients with in-hospital STEMI were compared with patients with out-of-hospital STEMI with a primary endpoint of 30-day major adverse cardiovascular events (MACE). Secondary endpoints included ischaemic times, all-cause mortality and major bleeding. RESULTS Of 7493 patients with PCI-treated STEMI, 494 (6.6%) occurred in-hospital. Patients with in-hospital STEMI were older (67.1 vs 62.4 years, p<0.001), more often women (32% vs 19.9%, p<0.001), with more comorbidities. Patients with in-hospital STEMI had higher 30-day MACE (20.4% vs 9.8%, p<0.001), mortality (12.1% vs 6.9%, p<0.001) and major bleeding (4.9% vs 2.3%, p<0.001), than patients with out-of-hospital STEMI. According to guideline criteria, patients with in-hospital STEMI achieved symptom-to-device times of ≤70 min and ≤90 min in 29% and 47%, respectively. Patients with out-of-hospital STEMI achieved door-to-device times of ≤90 min in 71%. Occurrence of STEMI while in hospital independently predicted higher MACE (adjusted OR 1.77, 95% CI 1.33 to 2.36, p<0.001) and 12-month mortality (adjusted OR 1.49, 95% CI 1.08 to 2.07, p<0.001). CONCLUSIONS Patients with in-hospital STEMI experience delays to reperfusion with significantly higher MACE and mortality, compared with patients with out-of-hospital STEMI, after adjustment for confounders. Focused strategies are needed to improve recognition and outcomes in this high-risk and understudied population

Increased Risk of Non-Q Wave Myocardial Infarction After Directional Atherectomy Is Platelet Dependent: Evidence From the EPIC Trial

AbstractObjectives. We sought to determine the effects of platelet glycoprotein IIb/IIIa receptor blockade on adverse outcomes, especially non-Q wave myocardial infarction, in patients undergoing directional atherectomy in the Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) trial.Background. Randomized trials comparing directional atherectomy with percutaneous transluminal coronary angioplasty (PTCA) have demonstrated modest benefits favoring atherectomy but at a cost of increased acute ischemic complications, notably non-Q wave myocardial infarction. The mechanism for this excess risk is unknown.Methods. Of 2,038 high risk patients undergoing coronary intervention in the EPIC trial, directional atherectomy was performed in 197 (10%). Patients randomly received the chimeric glycoprotein IIb/IIIa antibody 7E3 (c7E3), as a bolus or a bolus and 12-h infusion or placebo. Study end points included death, myocardial infarction, repeat intervention or bypass surgery.Results. Patients undergoing directional atherectomy had a lower baseline risk for acute complications but had a higher incidence of any myocardial infarction (10.7% vs. 6.3%, p = 0.021) and non-Q wave myocardial infarction (9.6% vs. 4.9%, p = 0.006). Bolus and infusion of c7E3 reduced non-Q wave myocardial infarctions by 71% after atherectomy (15.4% for placebo vs. 4.5% for bolus and infusion, p = 0.046). Non-Q wave myocardial infarction rates after PTCA were not affected by c7E3, although Q wave myocardial infarctions were reduced from 2.6% to 0.8% (p = 0.017).Conclusions. The EPIC trial confirmed the increased risk of non-Q wave myocardial infarction with directional atherectomy use compared with PTCA. A bolus and 12-h infusion of the glycoprotein IIb/IIIa receptor inhibitor c7E3 abolished this excess risk. Directional atherectomy-related non-Q wave myocardial infarction appears to be platelet aggregation dependent

Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness

<p>Abstract</p> <p>Background</p> <p>Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection (Jurriaans <it>et al</it>., <it>JAIDS </it>2008, <b>47:</b>69-73). The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection.</p> <p>Results</p> <p>Biological HIV-1 clones were derived from peripheral blood CD4 + T cells at different time point, and identified as the primary or secondary virus through sequence analysis. Replication competition assays were performed with selected virus pairs in PHA/IL-2 activated peripheral blood mononuclear cells (PBMC's) and analyzed with the Heteroduplex Tracking Assay (HTA) and isolate-specific PCR amplification. In both cases, we found a replicative advantage of the secondary HIV-1 strain over the primary virus. Full-length HIV-1 genomes were sequenced to find possible explanations for the difference in replication capacity. Mutations that could negatively affect viral replication were identified in the primary infecting strains. In patient L, the primary strain has two insertions in the LTR promoter, combined with a mutation in the <it>tat </it>gene that has been associated with decreased replication capacity. The primary HIV-1 strain isolated from patient P has two mutations in the LTR that have been associated with a reduced replication rate. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.</p> <p>Conclusions</p> <p>These preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.</p

Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL

Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin