Serial measurement of pulmonary mechanics assists in weaning from extracorporeal membrane oxygenation in neonates with respiratory failure

Extracorporeal membrane oxygenation (ECMO) is a highly invasive therapy for intractable neonatal respiratory failure, and serious complications may occur with increasing duration of bypass. Weaning from bypass is empirical at present. Thus, there is a need to accurately predict when infants can be successfully decannulated. We hypothesized that pulmonary mechanics would reflect lung recovery and, therefore, predict successful weaning from ECMO. We measured pulmonary mechanics daily in 22 neonates, at gestational age of 37.8 +/- 0.6 weeks (SE) requiring ECMO for severe respiratory failure (oxygen index 66 +/- 6). Pulmonary resistance (Rpul), dynamic compliance (Cdyn), and tidal volume (VT) were measured. Rpul did not predict lung recovery. Cdyn within 24 hours of starting ECMO was 0.3 +/- 0.04 ml/cm H2O. Cdyn within 24 hours of weaning from ECMO was 1.2 +/- 0.09 ml/cm H2O (p less than 0.001). All 22 infants had Cdyn greater than 0.6 ml/cm H2O at the time of decannulation, but four infants (20 percent) with Cdyn less than 0.6 ml/cm H2O could not be weaned from ECMO within 20 hours (p less than 0.01). Thus, a minimum Cdyn of 0.6 ml/cm H2O is associated with successful weaning from ECMO. Cdyn of 0.8 ml/cm H2O provided better overall discrimination between those who could be successfully weaned from ECMO. We conclude that serial measurement of dynamic pulmonary compliance predicts successful weaning from ECMO.     

Paclitaxel-coated balloon treatment for functionally nonsignificant residual coronary lesions after balloon angioplasty

There is limited data on the efficacy of paclitaxel-coated balloon (PCB) compared to stents for de novo coronary lesions. The purpose of this study was to compare the efficacy of PCB treatment with stent implantation for de novo coronary lesions after successful plain old balloon angioplasty (POBA) guided by fractional flow reserve (FFR). In 200 patients scheduled for elective percutaneous coronary intervention (PCI) for de novo lesions, FFR was measured after POBA (POBA–FFR). If POBA–FFR was ≥?0.75, patients were treated with PCB (PCB group, n?=?78) or stent (Stent group, n?=?73). If POBA–FFR was <?0.75, stent was implanted as planned (Reference group, n?=?42). The primary endpoint was late lumen loss at 9 months and the secondary endpoint was adverse cardiac events (cardiac death, myocardial infarction, target lesion thrombosis, or repeat revascularization) at 12 months follow-up. There was no between-group differences in the POBA–FFR (0.87?±?0.05 in PCB, 0.89?±?0.06 in stent, p?=?0.101). At 9 months, late lumen loss was significantly lower in the PCB group compared to the Stent group (0.05?±?0.33 vs. 0.59?±?0.76 mm, p?<?0.001). Adverse cardiac events were not different between the PCB, Stent and Reference groups (2.6, 5.5, and 9.5% respectively; p?=?0.430 for PCB vs. Stent group; p?=?0.229 for the reference vs. both other groups). PCB treatment guided by POBA–FFR showed excellent 9 months angiographic and functional results, as well as comparable 12 months clinical outcomes, compared with stent implantation for de novo coronary lesions.     

Seasonal and Geographic Patterns in Seeking Cardiovascular Health Information: An Analysis of the Online Search Trends

Objective

To ascertain whether temporal and geographic interest in seeking cardiovascular disease (CVD) information online follows seasonal and geographic patterns similar to those observed in real-world data.

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma

Human leukocyte antigen class I molecules expressed by tumor cells play a central role in the regulation of natural killer (NK) cell-mediated immune responses. The proteasome inhibitor bortezomib has demonstrated significant activity in multiple myeloma (MM). We hypothesized that treatment of MM with bortezomib results in the reduction of cell-surface expression of class I and thereby sensitizes MM to NK cell-mediated lysis. Here we report that bortezomib down-regulates class I in a time- and dose-dependent fashion on all MM cell lines and patient MM cells tested. Downregulation of class I can also be induced in vivo after a single dose of 1.0 mg/m(2) bortezomib. Bortezomib significantly enhances the sensitivity of patient myeloma to allogeneic and autologous NK cell-mediated lysis. Further, the level of decrease in class I expression correlates with increased susceptibility to lysis by NK cells. Clinically relevant bortezomib concentrations do not affect NK-cell function. Our findings have clear therapeutic implications for MM and other NK cell-sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells.     

Genetic basis of congenital generalized lipodystrophy

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by extreme lack of body fat and severe insulin resistance since birth. Recently, mutations have been reported in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2 or Seipin) genes in affected subjects from pedigrees linked to chromosomes 9q34 and 11q13, respectively. The AGPAT2 catalyses the acylation of the lysophosphatidic acid at the sn-2 position to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids. High expression of AGPAT2 mRNA in adipose tissue compared to other isoforms suggests that the mutations might affect the adipose tissue the most. The function of BSCL2 remains unknown. Several CGL pedigrees reveal no mutation in either of the above genes and are not linked to these loci, suggesting additional genetic loci for CGL. Thus, several distinct mechanisms can lead to extreme lack of adipose tissue in humans and cause CGL.     

Predictors and outcomes of ischemic stroke in reversible cerebral vasoconstriction syndrome

Journal of Neurology - The clinical factors predisposing to ischemic stroke in reversible cerebral vasoconstriction syndrome (RCVS) are unclear. In this observational cross-sectional study, we...