Percutaneous vein occlusion with small intestinal submucosa: an experimental pilot study in Swine and sheep

PURPOSE: The objective of this study was to investigate the feasibility, outcomes, and amount of small intestinal submucosa (SIS) material needed for embolization of jugular vein (JV) in a swine and sheep model. Our hypothesis was that SIS would cause vein occlusion. MATERIALS AND METHODS: The external JVs (EJV) in swine (n = 6) and JVs in sheep (n = 6) were occluded with SIS fan-folded compressed strips. After percutaneous puncture of the peripheral portion of the EJV or JV, a TIPS set was used to exit their lumen centrally through the skin. The SIS strips were delivered into the isolated venous segment with a pull-through technique via a 10-Fr sheath. Follow-up venograms were done immediately after placement and at the time of sacrifice at 1 or 3 months. Gross examinations focused on the EJV or JV and their surrounding structures. Specimens were evaluated by histology. RESULTS: SIS strip(s) placement was successful in all cases, with immediate vein occlusion seen in 23 of 24 veins (95.8%). All EJVs treated with two strips and all JVs treated with three or four strips remained closed on 1- and 3-month follow-up venograms. Two EJVs treated with one strip and one JV treated with two strips were partially patent on venograms at 1 and 3 months. There has been one skin inflammatory reaction. Necropsies revealed excluded EJV or JV segments with SIS incorporation into the vein wall. Histology demonstrated various stages of SIS remodeling with fibrocytes, fibroblasts, endothelial cells, capillaries, and inflammatory cells. CONCLUSION: We conclude that EJV and JV ablation with SIS strips using percutaneous exit catheterization is feasible and effective in animal models. Further exploration of SIS as vein ablation material is recommended.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke

BACKGROUND : Comparisons between younger and older stroke patients including comorbidities are limited. METHODS : Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger (and older patients (> 45 years). RESULTS : Among 1004 patients, 137 (14 %) were and a lower mean Charlson co-morbidity index (CCI), (0.18 versus 0.84; p < 0.0001). Tobacco use was more prevalent in the young (39 % versus 26 %; P < 0.0001). Large artery disease (2 % versus 21 %; p < 0.0001), small artery disease (3 % versus 12 %; p = 0.0019) and atrial fibrillation (1 % versus 17 %; p = 0.001) were less common in young patients, while other etiologies (31 % versus 9 %; p < 0.0001), patent foramen ovale or atrial septal defect (44 % versus 26 %; p < 0.0001), and cervical artery dissection (26 % versus 7 %; p < 0.0001) were more frequent. A favorable outcome (mRS 0 or 1) was more common (57.4 % versus 46.9 %; p = 0.023), and mortality (5.1 % versus 12 %; p = 0.009) was lower in the young. After regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. CONCLUSIONS : Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder)

This randomized trial compared procedural complications and 30-day clinical outcomes of 3 patent foramen ovale (PFO) closure devices (Amplatzer, Helex, and CardioSEAL-STARflex). It examined 660 patients (361 men, 299 women, mean age 49.3+/-1.9 years), with 220 patients per group. All patients had a history of paradoxical embolism. All PFO closures were successful technically. Exchange of devices for others was most frequently required for the Helex occluder (7 of 220) and 2 of 220 in either of the other groups. Three device embolizations in the Helex group were retrieved and replaced successfully. One patient with a Helex occluder developed a transient ischemic attack and recovered without treatment. A hemopericardium in that group was punctured without affecting the device. One tamponade in the Amplatzer group required surgical device explantation. In 8 of 660 patients in the CardioSEAL-STARflex group, thrombi resolved after anticoagulation. Sixteen patients (11 in the CardioSEAL-STARflex group, 3 in the Amplatzer group, and 2 in the Helex group) had episodes of atrial fibrillation. PFOs were closed completely in 143 of 220 patients (65%) in the Amplatzer group, 116 of 220 patients (52.7%) in the Helex group, and 137 of 220 patients (62.3%) in the CardioSEAL-STARflex group at 30 days with significant differences between the Helex and Amplatzer occluders (p=0.0005) and the Helex and CardioSEAL-STARflex occluders (p=0.0003). PFO closure can be performed safely with each device. In conclusion, the Helex occluder embolized more frequently. Device thrombus formation and paroxysmal atrial fibrillation were more common with the CardioSEAL-STARflex occluder.

Atrial fibrillation following device closure of patent foramen ovale

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.

Transseptal puncture for catheter ablation of atrial fibrillation after device closure of patent foramen ovale

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.

Percutaneous closure of patent foramen ovale for migraine headaches refractory to medical treatment

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.

Sex differences in cryptogenic stroke with patent foramen ovale

BACKGROUND: Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. METHODS: One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. RESULTS: The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. CONCLUSION: Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.

Device-less patent foramen ovale closure by radiofrequency thermal energy

The goal of this study was to assess the feasibility, safety and success of a system which uses radiofrequency energy (RFE) rather than a device for percutaneous closure of patent foramen ovale (PFO). METHODS: Sixteen patients (10 men, 6 women, mean age 50 years) were included in the study. All of them had a proven PFO with documented right-to-left shunt (RLS) after Valsalva manoeuvre (VM) during transoesophageal echocardiography (TEE). The patients had an average PFO diameter of 6 +/- 2 mm at TEE and an average of 23 +/- 4 microembolic signals (MES) in power M-mode transcranial Doppler sonography (pm-TCD), measured over the middle cerebral artery. An atrial septal aneurysm (ASA) was present in 7 patients (44%). Balloon measurement, performed in all patients, revealed a stretched PFO diameter of 8 +/- 3 mm. In 2 patients (stretched diameter 11 and 14 mm respectively, both with ASA >10 mm), radiofrequency was not applied (PFO too large) and the PFO was closed with an Amplatzer PFO occluder instead. A 6-month follow-up TEE was performed in all patients. RESULTS: There were no serious adverse events during the procedure or at follow-up (12 months average). TEE 6 months after the first RFE procedure showed complete closure of the PFO in 50% of the patients (7/14). Closure appeared to be influenced by PFO diameter, complete closure being achieved in 89% (7/8) with a balloon-stretched diameter < or =7 mm but in none of the patients >7 mm. Only one of the complete closure patients had an ASA. Of the remainder, 4 (29%) had an ASA. Although the PFO was not completely closed in this group, some reduction in the diameter of the PFO and in MES was documented by TEE and pm-TCD with VM. Five of the 7 residual shunt patients received an Amplatzer PFO occluder. Except for one patient with a minimal residual shunt, all showed complete closure of PFO at 6-month follow-up TEE and pm-TCD with VM. The other two refused a closure device. CONCLUSIONS: The results confirm that radiofrequency closure of the PFO is safe albeit less efficacious and more complex than device closure. The technique in its current state should not be attempted in patients with a balloon-stretched PFO diameter >7 mm and an ASA.

Late results after percutaneous closure of patent foramen ovale for secondary prevention of paradoxical embolism using the amplatzer PFO occluder without intraprocedural echocardiography: effect of device size

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.

The New Swiss Patent Ligitation System

Switzerland is about to implement a completely new patent litigation system, following the establishment of a new specialized federal patent trial court and the replacement of twenty-six cantonal codes of civil procedure with a single uniform federal code of civil procedure. This article provides an overview of the general structure and the most important features of the new patent litigation system that may be of interest to international patent litigants and litigators.

Patentability and Scope of Protection for DNA Sequence

Since the mapping of the human genome and the technical innovations in the field of biotechnology, patent law has gone through great controversies. Protection is required for an investor to make an investment but how broad should the given protection be? Whether the invention is a mi- cro-organism capable of dissolving crude oil, or the gene of a soya plant, the genetic engineering required for their production entails vast amounts of capi- tal. The policy in that respect is tailored by legislative acts and judicial decisions, ensuring a fair balance be- tween the interests of patent right holders and third parties. However, the policy differs from jurisdiction to jurisdiction, thus creating inconsistencies with re- gards to the given protection to the same invention, and as a result this could deter innovation and pro- mote stagnation. The most active actors shaping the patent policy on an international level are the patent offices of the United States of America, Japan and the European Patent Organization. These three patent offices have set up a cooperation programme in order to promote and improve efficiency with regards to their patent policies on a global scale. However, recent judicial de- velopments have shown that the policy in respect to the field of biotechnology differs between the patent regimes of the United States of America and the two- layer system of the European Patent Organisation/ the European Union.

Swiss Patent Jurisprudence 2012

The new Swiss Federal Patent Court, with nationwide first-instance jurisdiction over all civil patent matters, has been operating since 1 January 2012. This article reviews and contextualizes the most important patent cases the Swiss Federal Patent Court and the Swiss Federal Supreme Court. It concludes that the revamped Swiss patent litigation system has the potential of turning Switzerland into a competitive venue for the adjudication of patent matters in Europe.

Percutaneous closure of patent foramen ovale in cryptogenic embolism

BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy. METHODS We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population. RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56). CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.).