Background: Only few studies have investigated the relationship between the histopathology of retrieved thrombi and clinical outcomes. This study aimed to evaluate thrombus composition and its association with clinical, laboratory, and neurointerventional findings in patients treated by mechanical thrombectomy due to acute large vessel occlusion. Methods: At our institution, 79 patients were treated by mechanical thrombectomy using a stent retriever and/or aspiration catheter between August 2015 and August 2016. The retrieved thrombi were quantitatively analyzed to quantify red blood cells, white blood cells, and fibrin by area. We divided the patients into two groups – a fibrin-rich group and an erythrocyte-rich group – based on the predominant composition in the thrombus. The groups were compared for imaging, clinical, and neurointerventional data. Results: The retrieved thrombi from 43 patients with acute stroke from internal carotid artery, middle cerebral artery, or basilar artery occlusion were histologically analyzed. Erythrocyte-rich thrombi were present in 18 cases, while fibrin-rich thrombi were present in 25 cases. A cardioembolic etiology was significantly more prevalent among the patients with fibrin-rich thrombi than among those with erythrocyte-rich thrombi. Attenuation of thrombus density as shown on computed tomography images was greater in patients with erythrocyte-rich thrombi than in those with fibrin-rich thrombi. All other clinical and laboratory characteristics remained the same. Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers, shorter procedure times, a shorter time interval between arrival and recanalization, and a higher percentage of stent retrievers in the final recanalization procedure. The occluded vessels did not differ significantly. Conclusions: In this study, erythrocyte-rich thrombus was associated with noncardioembolic etiology, higher thrombus density, and reduced procedure time.

Psoriasis is an inflammatory disease with dynamic interactions between the immune system and the skin. The IL-23/Th17 axis plays an important role in the pathogenesis of psoriasis, although the exact contributions of IL-23 and IL-17 in vivo remain unclear. K5.Stat3C transgenic mice constitutively express activated Stat3 within keratinocytes, and these animals develop skin lesions with histological and cytokine profiles similar to those of human plaque psoriasis. In this study, we characterized the effects of anti-mouse IL-17A, anti-mouse IL-12/23p40, and anti-mouse IL-23p19 Abs on the development of psoriasis-like lesions in K5.Stat3C transgenic mice. Treatment with anti–IL-12/23p40 or anti–IL-23p19 Abs greatly inhibited 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperplasia in the ears of K5.Stat3C mice, whereas the inhibitory effect of an anti–IL-17A Ab was relatively less prominent. Treatment with anti–IL-12/23p40 or anti–IL-23p19 Abs markedly lowered transcript levels of Th17 cytokines (e.g., IL-17 and IL-22), β-defensins, and S100A family members in skin lesions. However, anti–IL-17A Ab treatment did not affect mRNA levels of Th17 cytokines. Crossing IL-17A–deficient mice with K5.Stat3C mice resulted in partial attenuation of 12-O-tetradecanoylphorbol-13-acetate–induced lesions, which were further attenuated by anti–IL-12/23p40 Ab treatment. FACS analysis of skin-draining lymph node cells from mice that were intradermally injected with IL-23 revealed an increase in both IL-22–producing T cells and NK-22 cells. Taken together, this system provides a useful mouse model for psoriasis and demonstrates distinct roles for IL-23 and IL-17.

ignificant tricuspid regurgitation (TR) has been reported in patients with a permanent pacemaker (PPM), [1][2][3][4][5] and the leads of such a device or those of an implantable cardioverter defibrillator (ICD) can be the primary cause of symptomatic TR. 6,7 However, in the clinical setting, the diagnosis of lead-induced TR can be challenging because conventional 2-dimensional echocardiography (2-DE) has limitations in identifying the anatomical relationship between the lead and the tricuspid leaflets. 7 The 3-dimensional echocardiography (3-DE) has been recently developed for assessing tricuspid valve morphology and pathology, including TR, [8][9][10][11] and case reports on its utility in the diagnosis of PPM-and ICD-lead-related TR have been published. 12,13 However, the ability of 3-DE to identify both the anatomical lead route through the tricuspid valve and lead-induced valve malfunction has not been studied systematically. Methods Patient PopulationIn 87 patients with PPM, ICD or cardiac resynchroniza- Circulation Journal Vol.72, September 2008tion therapy device, 3-DE studies were performed to evaluate the route of the leads and the presence of lead-related TR (Table 1). The underlying cardiac disease for which PPM implantation was required was complete or advanced atrioventricular block in 28 patients and sick sinus syndrome, including slow atrial fibrillation, in 22 patients, and for ICD implantation it was primary or secondary prevention of fatal cardiac arrhythmias in 17 patients. Cardiac resynchronization therapy devices with or without ICD were implanted in 20 patients with advanced heart failure. The study was approved by the local research ethics committee, and all patients gave written informed consent. Clinical Utility of 3-Dimensional Echocardiography in the Evaluation of Tricuspid Regurgitation Caused by Pacemaker LeadsYoshihiro Seo, MD; Tomoko Ishizu, MD; Hideki Nakajima, RDCS*; Yukio Sekiguchi, MD; Shigeyuki Watanabe, MD; Kazutaka Aonuma, MD Background This study evaluated the usefulness of 3-dimensional echocardiography (3-DE) for identifying permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead-related symptomatic tricuspid regurgitation (TR). Methods and ResultsEighty-seven patients underwent 3-DE examination: 50 patients with PPM, 17 with ICD, and 20 with cardiac resynchronization therapy devices. TR severity was classified as trivial/mild, moderate, or severe according to the ratio of TR area to right atrium area. The 3-DE identified the lead route and position at the tricuspid valve in 82 patients (94.2%). In 5 patients, images without lead-induced artifacts could not be obtained. TR severity was trivial/mild in 50 patients, moderate in 20 patients, and severe in 12 patients. In all patients with trivial/mild TR and all but 1 patient with moderate TR, leads were positioned on the annulus side between leaflets. Lead-induced obstruction to tricuspid valve closing was identified in 1 patient with moderate TR and in 7 of 12 patients with severe TR: 4 patients had...

Shiga toxin (Stx) is an enterotoxin produced by Shigella dysenteriae serotype 1 and enterohemorrhagic Escherichia coli, which binds specifically to globotriaosylceramide, Gb3, on the cell surface and causes cell death. We previously demonstrated that Stx induced apoptosis in human renal tubular cell line ACHN cells (Taguchi, T., Uchida, H., Kiyokawa, N., Mori, T., Sato, N., Horie, H., Takeda, T and Fujimoto, J. (1998) Kidney Int. 53, 1681-1688). To study the early signal transduction after Stx addition, Gb3-enriched microdomains were prepared from ACHN cells by sucrose density gradient centrifugation of Triton X-100 lysate as buoyant, detergent-insoluble microdomains (DIM). Gb3 was only recovered in DIM and was associated with Src family kinase Yes. Phosphorylation of tyrosine residues of proteins in the DIM fraction increased by 10 min and returned to the resting level by 30 min after the addition of Stx. Since the kinase activity of Yes changed with the same kinetics, Yes was thought to be responsible for the hyperphosphorylation observed in DIM proteins. Unexpectedly, however, all of the Yes kinase activity was obtained in the high density, detergent-soluble fraction. Yes was assumed to be activated and show increased Triton X-100 solubility in the early phase of retrograde endocytosis of Stx-Gb3 complex. Since Yes activation by the Stx addition was suppressed by filipin pretreatment, Gb3-enriched microdomains containing cholesterol were deeply involved in Stx signal transduction. Shiga toxin (Stx)1 of Shigella dysenteriae serotype 1 and enterohemorrhagic Escherichia coli is one of the major cause of hemolytic uremic syndrome (HUS). Stx consists of an A subunit of 32 kDa associated with five B subunits of 7.5 kDa each. The A subunits act to remove the adenine base at position 4324 of 28 S rRNA and are responsible for inactivation of protein synthesis and toxicity (2). The A subunits lacking B subunits, however, do not show any toxicity because of their inability to bind to the cell surface receptor. The B subunits bind specifically to cell surface glycosphingolipid (GSL) receptors-Gb3, 2 also known as CD77 or blood group P k (3). Once Stx is internalized, protein synthesis is suppressed, leading to cell death.Cell death is widely known to take place through two distinctive processes, necrosis or apoptosis. In contradiction to Williams's report (4), a number of recent studies have clearly demonstrated that Stx induces apoptosis in several different cell types, including Burkitt's lymphoma cells (5), Vero cells (6), human renal tubular derived ACHN cells (1), and normal human renal tubular epithelial cells (7,8). Especially, the later two studies indicate the importance of apoptotic cell death as one mechanism of damage to renal epithelium in the pathogenesis of HUS. Although the B subunit has no inhibitory effect on protein synthesis, a series of studies indicates that it alone participate to transduce cell signaling and can induce apoptosis in some instances such as Burkitt's lymphoma (5, 9). These reports en...

Background-In patients with atrial fibrillation (AF), most thrombus forms in the left atrial appendage (LAA). However, the relation of LAA morphology with LAA thrombus is unknown. Methods and Results-We prospectively enrolled 633 consecutive patients who were candidates for catheter ablation for symptomatic drug-resistant AF. Transesophageal echocardiography (TEE) was performed to assess LAA thrombus. LAA structure was assessed by 3-dimensional TEE. LAA orifice area, depth, volume, and number of lobes were measured on reconstructed 3-dimensional images. Clinical characteristics and echocardiographic measures were compared to determine variables predicting LAA thrombus.