Mechanical Thrombectomy for Acute Ischemic Stroke in the Cardiac Catheterization Laboratory.

OBJECTIVES: The aim of this study was to determine the feasibility of establishing a mechanical thrombectomy (MT) program for acute ischemic stroke in a community hospital using interventional cardiologists working closely with neurologists. BACKGROUND: American Heart Association/American Stroke Association 2018 guidelines give a Class I (Level of Evidence: A) recommendation for MT in eligible patients with large vessel occlusion stroke. Improvement in neurological outcomes with MT is highly time sensitive. Most hospitals do not have trained neurointerventionalists to perform MT, leading to treatment delays that reduce the benefit of reperfusion therapy. METHODS: An MT program based in the cardiac catheterization laboratory was developed using interventional cardiologists with ST-segment elevation myocardial infarction teams. RESULTS: Forty patients underwent attempted MT for acute ischemic stroke. An additional 5 patients who underwent angiography did not undergo attempted thrombectomy, because of absence of target thrombus (n = 4) or unsuitable anatomy (n = 1). Median National Institutes of Health Stroke Scale score prior to MT was 19 and at discharge was 7. TICI (Thrombolysis In Cerebral Infarction) grade 2b or 3 flow was restored in 80% of patients (32 of 40). At 90 days, 55% of patients (22 of 40) were functionally independent (modified Rankin score ≤2). In-hospital mortality was 13% (5 of 40). Symptomatic intracranial hemorrhage occurred in 15% of patients (6 of 40). Major vascular complications occurred in 5% of patients (2 of 40). CONCLUSIONS: MT can be successfully performed by interventional cardiologists with carotid stenting experience working closely with neurologists in hospitals lacking formally trained neurointerventionists. This model has the potential to increase access to timely care for patients with acute ischemic stroke.

Contrasting effects of ERK on tight junction integrity in differentiated and under-differentiated Caco-2 cell monolayers.

ERK (extracellular-signal-regulated kinase) activation leads to disruption of tight junctions in some epithelial monolayers, whereas it prevents disruption of tight junctions in other epithelia. The factors responsible for such contrasting influences of ERK on tight junction integrity are unknown. The present study investigated the effect of the state of cell differentiation on ERK-mediated regulation of tight junctions in Caco-2 cell monolayers. EGF (epidermal growth factor) potentiated H2O2-induced tight junction disruption in under-differentiated cell monolayers, which was attenuated by the MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] inhibitor U0126. In contrast, EGF prevented H2O2-induced disruption of tight junctions in differentiated cell monolayers, which was also attenuated by U0126. Knockdown of ERK1/2 enhanced tight junction integrity and accelerated assembly of tight junctions in under-differentiated cell monolayers, whereas it had the opposite effect in differentiated cell monolayers. Regulated expression of wild-type and constitutively active MEK1 disrupted tight junctions, and the expression of dominant-negative MEK1 enhanced tight junction integrity in under-differentiated cells, whereas contrasting responses were recorded in differentiated cells. EGF prevented both H2O2-induced association of PP2A (protein phosphatase 2A), and loss of association of PKCζ (protein kinase Cζ), with occludin by an ERK-dependent mechanism in differentiated cell monolayers, but not in under-differentiated cell monolayers. Active ERK was distributed in the intracellular compartment in under-differentiated cell monolayers, whereas it was localized mainly in the perijunctional region in differentiated cell monolayers. Thus ERK may exhibit its contrasting influences on tight junction integrity in under-differentiated and differentiated epithelial cells by virtue of differences in its subcellular distribution and ability to regulate the association of PKCζ and PP2A with tight junction proteins.

Correlation between serogroup, in vitro biofilm formation and elaboration of virulence factors by uropathogenic Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of catheter-associated urinary tract infections (UTIs), associated with high mortality and morbidity. In this study, 50 P. aeruginosa isolates from urine of patients with UTIs were serotyped according to the international antigenic typing system. The majority of the isolates (34%) belonged to serogroup O11, whereas 22%, 10%, 8%, 8%, 6%, 6%, 4% and 2% strains belonged to serogroups OII, O6, O1, O8, O7/8, O3, O4 and O15, respectively. Uroisolates belonging to serogroup O11 were strong biofilm producers, whereas serogroup O6 were weak biofilm producers. O11 serogroup uroisolates also showed increased adhesion to uroepithelium and elaborated higher levels of all the virulence factors. A strong correlation between serotype, in vitro biofilm formation and elaboration of virulence factors was observed. The data suggest that differences in virulence potential according to serotype should be taken into account to design effective preventive strategies against P. aeruginosa-induced UTIs.

Contribution of macrophage secretory products to urovirulence of Pseudomonas aeruginosa.

Macrophages form one of the first lines of defense on mucosal surfaces like urinary tract, providing protection against pathogens. These cells pour their secretory products, which include a cocktail of biomolecules, at the site of infection. In the present investigation, the effect of macrophage secretory products (MSPs) obtained after interaction of macrophages with Pseudomonas aeruginosa on the virulence of this organism in planktonic and biofilm cell mode was assessed employing a mouse model of ascending pyelonephritis. When urinary tract infection (UTI) was established with P. aeruginosa grown in the presence of 30% MSPs, the extent of pyelonephritis was enhanced. Of the two cell forms, biofilm cells had an edge over the planktonic cells with respect to in vivo virulence. The enhanced virulence of MSP-grown P. aeruginosa may be attributed to increased production of quorum-sensing systems as well as increased adherence to uroepithelial cells and evasion of phagocytosis. The results of the present study reveal that macrophages can play a key role during the course of UTI, not only through their phagocytic activity, but also through effects mediated by their secretory products. Utilization of MSPs by P. aeruginosa can have far-reaching consequences, including chronicity and recurrence of infections caused by this pathogen.

Urinary tract infections caused by Pseudomonas aeruginosa: a minireview.

Urinary tract infections (UTIs) are a serious health problem affecting millions of people each year. Infections of the urinary tract are the second most common type of infection in the body. Catheterization of the urinary tract is the most common factor, which predisposes the host to these infections. Catheter-associated UTI (CAUTI) is responsible for 40% of nosocomial infections, making it the most common cause of nosocomial infection. CAUTI accounts for more than 1 million cases in hospitals and nursing homes annually and often involve uropathogens other than Escherichia coli. While the epidemiology and pathogenic mechanisms of uropathogenic Escherichia coli have been extensively studied, little is known about the pathogenesis of UTIs caused by other organisms like Pseudomonas aeruginosa. Scanty available information regarding pathogenesis of UTIs caused by P. aeruginosa is an important bottleneck in developing effective preventive approaches. The aim of this review is to summarize some of the advances made in the field of P. aeruginosa induced UTIs and draws attention of the workers that more basic research at the level of pathogenesis is needed so that novel strategies can be designed.