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Microscopic pulmonary tumor embolism (MPTE) is an uncommon cause of dyspnea in patients with cancer and one of the most difficult to diagnose. MPTE is a syndrome that is pathologically characterized by the occlusion of small pulmonary arteries and arterioles by aggregates of tumor cells. Because the clinical picture resembles that of thromboembolic disease, it is rarely recognized before death. The most common clinical symptom is subacute progressive dyspnea over weeks to months. We recently observed a case of MPTE of exceptional interest as the patient was under aggressive anticoagulant treatment and developed fulminant pulmonary hypertension with fatal right heart failure.

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Two young women with angiographically normal coronary arteries suffered an acute myocardial infarction. Both were found to have a patent foramen ovale (PFO), the likely pathway of a paradoxical embolus causing the infarction. The PFOs were diagnosed and closed percutaneously with an Amplatzer PFO Occluder during the emergency coronary angiography.

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OBJECTIVES: To carry out long-term follow-up after percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. DESIGN: Prospective cohort study. SETTING: Single tertiary care centre. PARTICIPANTS: 525 consecutive patients (mean (SD) age 51 (12) years; 56% male). INTERVENTIONS: Percutaneous PFO closure without intraprocedural echocardiography. MAIN OUTCOME MEASURES: Freedom from recurrent embolic events. RESULTS: A mean (SD) of 1.7 (1.0) clinically apparent embolic events occurred for each patient, and 186 patients (35%) had >1 event. An atrial septal aneurysm was associated with the PFO in 161 patients (31%). All patients were followed up prospectively for up to 11 years. The implantation procedure failed in two patients (0.4%). There were 13 procedural complications (2.5%) without any long-term sequelae. Contrast transoesophageal echocardiography at 6 months showed complete closure in 86% of patients, and a minimal, moderate or large residual shunt in 9%, 3% and 2%, respectively. Patients with small occluders (<30 mm; n = 429) had fewer residual shunts (small 11% vs large 27%; p<0.001). During a mean (SD) follow-up of 2.9 (2.2) years (median 2.3 years; total 1534 patient-years), six ischaemic strokes, nine transient ischaemic attacks (TIAs) and two peripheral emboli occurred. Freedom from recurrent stroke, TIA, or peripheral embolism was 98% at 1 year, 97% at 2 years and 96% at 5 and 10 years, respectively. A residual shunt (hazard ratio = 3.4; 95% CI 1.3 to 9.2) was a risk factor for recurrence. CONCLUSIONS: This study attests to the long-term safety and efficacy of percutaneous PFO closure guided by fluoroscopy only for secondary prevention of paradoxical embolism in a large cohort of consecutive patients.

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Right atrial perforation can lead to tamponade and death. Closure devices are used for sealing of shunts in the heart. We describe an indwelling catheter that caused perforation of the right atrium and was treated with a percutaneous closure device.

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OBJECTIVES: Recurrent embolic events after device closure of patent foramen ovale (PFO) have been related to incomplete closure. Another cause could be atrial fibrillation (AF). The aim of this study was to determine the incidence of AF in stroke patients after PFO closure. METHODS: Consecutive patients with device closure of a PFO after a stroke or transient ischemic attack and control patients with stroke underwent 7-day event loop recordings 3 and 6 months after PFO closure or stroke, respectively. RESULTS: Forty patients treated by PFO device closure 96 +/- 68 days after cryptogenic ischemic stroke and 70 control patients with ischemic stroke of other etiologies (known AF excluded) were compared. AF was identified in 6 patients (15%) of the treated group and in 12 control patients (17%, p = 0.77). In multivariate analysis, the presence of an occluder device was not an independent risk factor for AF. CONCLUSIONS: The incidence of AF is high after device closure of a PFO in stroke patients and similar to that in patients with stroke of non-PFO etiology and, hence, with no device. Further studies are required to determine the risk of thromboembolism and the optimal treatment in patients developing AF after device closure of a PFO.

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The technique of transseptal puncture for catheter ablation of atrial fibrillation after percutaneous closure of a foramen ovale with the Amplatzer Occluder is demonstrated based on 2 representative cases.

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BACKGROUND: Patent foramen ovale (PFO) has been linked to migraine, and several retrospective studies reported an improvement in migraine prevalence or frequency after PFO closure for other reasons, mostly for secondary prevention of paradoxical embolism or following diving accidents. We investigated the outcome of patients undergoing PFO closure solely for migraine headaches refractory to medical treatment. METHODS: Seventeen patients (age 44 +/- 12 years; 76% female; one atrial septal aneurysm) underwent percutaneous PFO closure using the Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, MN). An 18-mm device was used in two patients, a 25-mm device in 13, and a 35-mm device in two. The interventions were solely guided by fluoroscopy, without intraprocedural echocardiography. RESULTS: All implantation procedures were successful. There were no peri-procedural complications. Contrast transesophageal echocardiography after Valsalva maneuver at 6 months showed complete PFO closure in 16 patients (94%), whereas a minimal residual shunt persisted in one (6%). During 2.7 +/- 1.5 years of follow-up, no deaths and no embolic events occurred. After PFO closure, migraine headaches disappeared in four patients (24%), and improved in eight additional patients (47%). Three patients (18%) reported a decrease of their headaches by 75%, three patients (18%) a decrease of 50%, and two patients (12%) a decrease of 25%, while headaches remained unchanged in five patients (29%). No patient experienced worsening headaches. Moreover, the prevalence of migraine with aura decreased from 82 to 24% (P = 0.002). CONCLUSIONS: These results suggest that percutaneous PFO closure durably alters the spontaneous course of shunt associated migraine.

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The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

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OBJECTIVES: We sought to assess the safety and clinical efficacy of patent foramen ovale (PFO) closure under fluoroscopic guidance only, without intraprocedural echocardiography. BACKGROUND: Percutaneous PFO closure has been shown to be safe and feasible using several devices. It is generally performed using simultaneously fluoroscopic and transesophageal or intracardiac echocardiographic guidance. Transesophageal echocardiography requires sedation or general anesthesia and intubation to avoid aspiration. Intracardiac echocardiography is costly and has inherent risks. Both lengthen the procedure. The Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, Minnesota) can be safely implanted without echocardiographic guidance. METHODS: A total of 620 patients (51 +/- 12 years; 66% male) underwent PFO closure using the Amplatzer PFO Occluder for secondary prevention of presumed paradoxical embolism. Based on size and mobility of the PFO and the interatrial septum, an 18-mm device was used in 50 patients, a 25-mm device in 492, and a 35-mm device in 78. RESULTS: All procedures were successful, with 5 procedural complications (0.8%): 4 arteriovenous fistulae requiring elective surgical correction, and 1 transient ischemic attack. Contrast transesophageal echocardiography at 6 months showed complete closure in 91% of patients, whereas a minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. During a mean follow-up period of 3.0 +/- 1.9 years (median: 2.6 years; total patient-years: 1,871), 5 ischemic strokes, 8 transient ischemic attacks, and no peripheral emboli were reported. Freedom from recurrent ischemic stroke, transient ischemic attack, or peripheral embolism was 99% at 1 year, 99% at 2 years, and 97% at 5 years. CONCLUSIONS: The Amplatzer PFO Occluder affords excellent safety and long-term clinical efficacy of percutaneous PFO closure without intraprocedural echocardiography.

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AIMS: Currently available devices for transcatheter closure of patent foramen ovale (PFO) which rely on a permanent implant have limitations, including late complications. The study objective was to evaluate the safety, feasibility, and effectiveness of the PFx Closure System, the first transcatheter technique for PFO closure without an implantable device. METHODS AND RESULTS: A prospective study of 144 patients was conducted at nine clinical sites from October 2005 through August 2007. All patients had a history of cryptogenic stroke, transient ischemic attack, migraines, or decompression illness. The mean balloon stretched diameter of the PFO was 7.9 +/- 2.5 mm. Technical success (successful application of radiofrequency energy) was achieved in 130 patients. One patient required a transfusion as a result of blood loss during the procedure. There were no other major procedural complications. There were no recurrent strokes, deaths, conduction abnormalities, or perforations following the procedure. At a mean follow-up of 6 months, successful closure was achieved in 79 patients (55%). In PFOs with balloon sized or stretched diameters less than 8 mm, the closure rate was 72% (53/74). CONCLUSION: This study demonstrates that transcatheter closure of a PFO without a permanent implant is technically feasible and safe. Further technique and device modifications are required to achieve higher closure rates.

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A one-pot, general synthesis of highly functionalized quateraryls through carbanion-induced, base-catalyzed ring transformation of 5,6-diaryl-2H-pyran-2-ones and core-substituted phenylacetones is delineated. These conversions were found to give diversely functionalized benzenes bearing peripheral aryl rings, some of which possess inherent atropisomerism. Exemplarily for one of the quateraryls, the optical resolution of the respective atropo-enantiomers by HPLC on a chiral phase and the assignment of their absolute axial configurations succeeded by LC-CD coupling in combination with semiempirical CNDO/S and TDDFT CD calculations. This synthetic approach offers – in a transition metal-free environment – high flexibility in the construction of quateraryls with the desired conformational freedom along the molecular axis, which may help in exploring and developing new potential ligands for asymmetric synthesis.