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Impending paradoxical embolism (IPDE) is a right heart thrombus (RHT), in times of elevated pulmonary arterial pressure, that is trapped in a patent foramen ovale (PFO) Myers et al. (2010) (3). We present a case that highlights our multidisciplinary approach in a patient with IPDE with cardiogenic shock from pulmonary embolism (PE). • Diagnosis of paradoxical embolism (PDE) before advancements in imaging was made presumptively as it was impossible to visualize a clot as it traverses a cardiac defect. With the advent of echocardiography, it is now possible to visualize right heart thrombus (RHT) in vivo and see as it traverses a cardiac defect. This phenomenon is known as an impending paradoxical embolism (IPDE) • IPDE, must be acted promptly as it can embolize systemically. Literature regarding IPDE is scant but shows that surgical intervention is superior to systemic thrombolysis. However, percutaneous interventions have not been studied. • The patient was unable to undergo systemic thrombolysis or surgical intervention because of patient's history of Moyamoya, which proved too great a risk. Thus, a percutaneous approach involving interventional radiology (IR) and structural cardiology was employed. • Patient was initiated on venoarterial extracorporeal membrane oxygenation, a cardioembolic protection device was placed, and the IPDE was aspirated via an Angiovac. Once aspirated, the cardiac defect was occluded percutaneously. Aspiration thrombectomy of the massive pulmonary embolisms was then completed by IR. • As it stands now, the literature regarding which approach is superior is lacking. With advancements in echocardiography, more and more IPDE will be discovered. It is imperative to delineate whether a surgical, percutaneous, or systemic thrombolysis approach should be utilized. Further research should be undertaken. [ABSTRACT FROM AUTHOR]

About 300 million adults undergo non-cardiac surgery annually. Although, in this setting, the incidence of perioperative stroke is low, the absolute number of patients experiencing a stroke is substantial. Furthermore, most patients with this complication will die or end up with severe disability. Covert brain infarctions are more frequent than overt strokes and are associated with postoperative delirium, cognitive decline, and cerebrovascular events at 1 year after surgery. Evidence shows that traditional stroke risk factors including older age, hypertension, and atrial fibrillation are also associated with perioperative stroke; previous stroke is the strongest risk factor for perioperative stroke. Increasing evidence also suggests the pathogenic role of perioperative events, such as hypotension, new atrial fibrillation, paradoxical embolism, and bleeding. Clinicians involved in perioperative care should be aware of this evidence on prevention strategies to improve patient outcomes after non-cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Patent foramen ovale (PFO) is associated with perioperative stroke in noncardiac surgery. The magnitude of this association was assessed in a systematic review and meta-analysis.Methods: Electronic databases were searched up to June 2022 for studies assessing the association between patent foramen ovale and perioperative stroke in adult patients undergoing noncardiac surgery. The primary analysis was limited to studies reporting effect estimates adjusted for significant clinical confounders. We calculated the adjusted odds ratio (aOR) and 95% confidence interval (CI).Results: We included nine retrospective and two prospective observational studies, including 21 257 082 patients. The presence of a patent foramen ovale was independently associated with stroke at 30 days after surgery (aOR=6.68 [95% CI: 3.51-12.73]; P<0.001) and at longest follow-up available (aOR=7.36 [95% CI: 3.56-15.21]; P<0.001). The odds of stroke at 30 days varied according to surgical specialty: neurosurgery (aOR=4.52 [95% CI: 3.17-6.43]), vascular surgery (aOR=7.15 [95% CI: 2.52-20.22]), thoracic surgery (aOR=10.64 [95% CI: 5.97-18.98]), orthopaedic surgery (aOR=11.85 [95% CI: 5.38-26.08]), general surgery (aOR=14.40 [95% CI: 10.88-19.06]), and genitourinary surgery (aOR=17.28 [95% CI: 10.36-28.84]).Conclusions: The presence of a patent foramen ovale is associated with a large and consistent increase in odds of stroke across all explored surgical settings. Prospective trials should further explore this association by systematically assessing patent foramen ovale and stroke prevalence and identifying a specific population at risk. This is crucial for the elaboration of prevention plans and may improve perioperative outcomes. [ABSTRACT FROM AUTHOR]

Paradoxical embolism from right-to-left shunt through atrial septal defect (ASD) and patent foramen ovale (PFO) is a well-accepted cause of "cryptogenic" strokes (CS). To better understand the pathogenic role of ASD, we compared ASD patients with CS having a high and low likelihood of being PFO-related. In the Acute Stroke Registry and Analysis of Lausanne, we calculated prevalence of PFO and ASD in CS patients undergoing echocardiography, and calculated odds ratios (OR) when compared to non-CS. Using the Risk of Paradoxical Embolism (RoPE) score, we divided CS PFO patients in high (HL-PFO, RoPE 8-10) and low-likelihood (LL-PFO, RoPE 0-4) PFO-related stroke. We then performed univariate comparison of epidemiological, clinical and radiological variables of ASD patients with both PFO groups. Among all CS, prevalence of ASD and PFO were 1.3% and 36.8% respectively. When compared to non-CS, ASD and PFO were associated with CS (OR of 5.2, CI= 1.6-16.6, and 2.8, CI= 2.1-3.8). Compared with HL-PFO, ASD patients were older, more often female, had more cardiovascular risk factors and silent strokes. Compared with LL-PFO, ASD patients were younger, more often female, and had less risk factors. No differences were found for clinical and radiological characteristics and clinical outcome. ASD is a rare stroke risk factor for CS. Since characteristics of such patients lie in-between high and low-likelihood paradoxical PFO-strokes, a thorough work-up for other stroke mechanisms is warranted. Individual evaluation of the likelihood of the ASD being causative for stroke may be preferable over routine ASD closure. [ABSTRACT FROM AUTHOR]

This paper sought to evaluate the occurrence of decompression sickness (DCS) after the application of a patent foramen ovale (PFO) screening and risk stratification strategy. PFO is associated with an increased risk of DCS. Recently, transcatheter closure was reported to reduce DCS occurrence in divers with a high-grade shunt. However, to date, there are no data regarding the effectiveness of any PFO screening and risk stratification strategy for divers. A total of 829 consecutive divers (age 35.4 ± 10.0 years, 81.5% men) were screened for PFO by means of transcranial color-coded sonography in the DIVE-PFO (Decompression Illness Prevention in Divers with a Patent Foramen Ovale) registry. Divers with a high-grade PFO were offered either catheter-based PFO closure (the closure group) or advised conservative diving (high grades). Divers with a low-grade shunt were advised conservative diving (low grades), whereas those with no PFO continued unrestricted diving (controls). A telephone follow-up was performed. To study the effect of the screening and risk stratification strategy, DCS occurrence before enrollment and during the follow-up was compared. Follow-up was available for 748 (90%) divers. Seven hundred and 2 divers continued diving and were included in the analysis (mean follow-up 6.5 ± 3.5 years). The DCS incidence decreased significantly in all groups, except the controls. During follow-up, there were no DCS events in the closure group; DCS incidence was similar to the controls in the low-grade group (HR: 3.965; 95% CI: 0.558-28.18; P = 0.169) but remained higher in the high-grade group (HR: 26.170; 95% CI: 5.797-118.160; P < 0.0001). The screening and risk stratification strategy using transcranial color-coded sonography was associated with a decrease in DCS occurrence in divers with PFO. Catheter-based PFO closure was associated with a DCS occurrence similar to the controls; the conservative strategy had a similar effect in the low-grade group, but in the high-grade group the DCS incidence remained higher than in all other groups. [Display omitted] [ABSTRACT FROM AUTHOR]

Right atrial thrombi are rarely found straddling a patent foramen ovale (PFO). A thrombus straddling a PFO (TSPFO), also known as impending paradoxical embolism, is a medical emergency associated with up to 11.5% risk of death within 24 h of being diagnosed. We hypothesized that acute myocardial infarction (MI) and ischemic stroke (IS) diagnosed upon the admission of patients with TSPFO are associated with increased risk of death. We also investigated if specific acute therapies are associated with reduced in-hospital mortality. We performed a systematic search including case reports and series of adult patients with TSPFO published from 1950 to October 30, 2020. We gathered patient-level data and we applied a logistic regression model to evaluate on the risk of in-hospital death. We performed time-trends and several sensitivity analyses. We included 386 cases with a TSPFO comprised in 359 publications. The median age was 61 years and 51.2% were females. Fifty (13.0%) patients died during hospital stay, 82 (21.2%) had an acute IS, and 18 (4.6%) had an acute MI diagnosed upon admission. Acute MI (OR 7.83, 95%CI 2.70–22.7; P < 0.0001), but not IS, was associated with increased risk of death. Right atrial thrombectomy was associated with a 65% decreased in-hospital mortality (OR 0.35, 95%CI 0.18–0.70, P = 0.003). Results remained unchanged on sensitivity analyses. In this systematic review of 386 cases of TSPFO, acute MI but not IS was associated with 8-fold increased risk of death, while surgical thrombectomy was associated with a significant 65% reduction of in-hospital mortality. • Patients with TSPFO have an elevated in-hospital mortality (13.0%) Ischemic stroke (21.2%) and myocardial infarction (4.7%) are frequent after a TSPFO. • Myocardial infarction increases the risk of death by 8-fold in TSPFO. • In hospital death is 65% lower in TSPFO after the surgical removal of the thrombus. • Proximal coronary artery embolic occlusion causes most myocardial infarctions in TSPFO. [ABSTRACT FROM AUTHOR]

Background: A patent foramen ovale (PFO) has been associated with embolic strokes and transient ischemic attacks (TIAs). Catheter closure of PFO is effective in preventing recurrent events. Residual shunts and procedure or device related complications can occur, including atrial fibrillation and thrombus formation. This study examines the initial experience with a new PFO closure device, the IrisFIT PFO-Occluder (Lifetech Scientific, Shenzhen, China).Methods: 95 patients with indications for PFO closure underwent percutaneous closure with the IrisFIT PFO-Occluder. The primary endpoint was the rate of accurate device placement with no/small residual shunt at 3 or 6 months follow-up. All patients underwent transoesophageal echocardiography (TEE) after 1 to 6 months. In case of a residual shunt, an additional TEE was performed after 12 months. Clinical follow-up was performed up to a mean of 33.1 ± 3.6 months.Results: The device was successfully implanted in 95 (100%) patients with no relevant procedural complications. At final TEE follow-up (7.6 ± 3.9 months) the effective closure rate was 96.8% with 1 moderate and 2 large residual shunts. There were 8 cases of new onset atrial fibrillation and 2 TIAs. There were no cases of device embolization or erosion.Conclusion: The IrisFIT occluder is a new PFO closure device with several advantages compared to other devices. In this small study cohort, technical success rate, closure rate and adverse event rate were comparable to other devices. The rate of new onset atrial fibrillation was higher in comparison to other studies and warrants further investigation. [ABSTRACT FROM AUTHOR]

Coronary artery embolism is an uncommon cause of myocardial infarction (MI). Among several etiologies of coronary embolism, we mention a very rare cause which is the paradoxical embolism via patent foramen ovale (PFO). It interests generally youngest people without cardiac risk factors. We report three cases who presented ST-elevation MI (STEMI) due to paradoxical embolism with high risk PFO that can justify embolic infarction. The aim of this article is to define the high risk PFO, to establish causal link between PFO and embolic events and to guide therapeutic management. [ABSTRACT FROM AUTHOR]

Small atrial septal defects are usually asymptomatic and routinely followed in young patients. However, closure of atrial septal defects becomes necessary if defects fail to close or if size of the defects results in hemodynamically significant shunting. Patients with untreated left to right shunting are at risk for long term complications. Including enlargement of right heart structures, tricuspid annular dilatation with secondary valvular insufficiency, and heart failure. Older adult patients may be at risk for paradoxical embolism. Patients are generally referred for surgery before school age. Older patients may be considered for device closure. Nonetheless, in some cases, patients are not diagnosed early or are not followed up sufficiently, leading to progression of disease and discovery in adulthood. We present three adult cases with large atrial septal defects associated with tricuspid valve regurgitation managed surgically. • Tricuspid valve regurgitation associated with ostium secundum atrial septal defects may be symptomatic • Untreated atrial septal defects with associated tricuspid valve regurgitation may lead to right heart failure • There is no consensus management of tricuspid valve regurgitation associated with atrial septal defects • Surgical treatment of tricuspid valve regurgitation may be considered at the time of atrial septal defect closure in adults [ABSTRACT FROM AUTHOR]

Pulmonary hypertension is associated with atrial fibrillation and paradoxical embolism. Yet, the association between pulmonary hypertension and stroke has not been well studied. We reviewed Medline and Embase from inception to December 1, 2018, to identify observational studies reporting prevalence of stroke in adult patients with pulmonary hypertension. We sought studies that included patients with pulmonary hypertension secondary to any etiology except left heart failure, and excluded studies that reported rates of perioperative stroke. We conducted random effects meta-analyses to obtain pooled prevalence of stroke in patients with pulmonary hypertension, and pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without. We included 14 studies including 32,523 participants of which 2976 (9.2%) had pulmonary hypertension, and 727 (2.2%) had a stroke. The pooled prevalence of stroke in patients with pulmonary hypertension was 8.0% [95% confidence interval (CI), 5.1%–10.9%, I 2 91.9]. The pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without was 1.46 (95% CI, 1.07–1.99, I 2 55.6, n = 7 studies). Stroke is a major non-cardiac morbidity in patients with pulmonary hypertension, requiring further evaluation to determine its etiology, and measures to reduce its risk. • We systematically reviewed prevalence of stroke (ischemic or hemorrhagic) in patients with pulmonary hypertension. • Approximately, 1 in 13 patients with pulmonary hypertension had a stroke. • The odds of having a stroke was 46% higher in patients with pulmonary hypertension compared to those without. • Stroke must be recognized as a major non-cardiac morbidity in patients with pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Background: Patent foramen ovale (PFO) is a potential mechanism for paradoxical embolism in cryptogenic ischaemic stroke or transient ischaemic attack (TIA). PFO is typically demonstrated with agitated saline ("bubble study", BS) during echocardiography. We hypothesised that the BS is frequently requested in patients that have a readily identifiable cause of stroke, that any PFO detected is likely incidental, and its detection often does not alter management.Methods: This was a retrospective observational study of patients with recent ischaemic stroke/TIA referred for a BS. Patient demographics, stroke risk factors, vascular/cerebral imaging results and transoesophageal echocardiogram (TOE) reports were recorded. A "modified" Risk of Paradoxical Embolism (RoPE) score was calculated. Change in management was defined as antiplatelet/anticoagulant therapy alteration or referral for PFO closure. Bubble Study complications were recorded.Results: Among 715 patients with ischaemic stroke/TIA referred for a BS, 8.7% had atrial fibrillation and 9.2% had carotid stenosis ≥70%. At least three stroke risk factors were present in 39.3% and only 47.1% of patients screened had a "modified" RoPE score of >5. A PFO was detected in 248 patients of whom only 31% (77/248) had a subsequent change in management. Of BS performed, 1/924 patients (0.1%) suffered a TIA as a complication.Conclusions: The echocardiographic BS is frequently performed in patients that have a readily identifiable cause of stroke and whose PFO unlikely relates to the stroke/TIA. Bubble Study findings resulted in a change in management in the minority. The procedure is safe but the complication rate warrants informed consent. [ABSTRACT FROM AUTHOR]

Background and Purpose: The routine use of percutaneous transcatheter patent foramen ovale closure (PPFOC) to prevent recurrent stroke in patients with cryptogenic stroke is still a matter of debate after completion major randomized controlled trials (RCTs).Methods: The fragility index of RCTs evaluating effect of PPFOC against medial therapy alone in stroke prevention was calculated to assess the robustness of statistically significant findings.Results: Literature search with PubMed identifies 6 RCTs on PPFOC. Median number of patients who underwent PPFOC and medical treatment were 340 and 229, respectively. Median number of the patients lost to follow-up was 20 in PPFOC and 18 in medical group. Fragility index was 0 for 4 studies. Median fragility index was also 0 for both "stroke" (interquartile range: 0-5.3) and "combined stroke and TIA" (interquartile range: 0-2) endpoints. In all studies except CLOSE, fragility index was smaller than or equal to the number of the subjects lost to follow-up.Conclusions: Recent positive results of PFO closure studies should be interpreted cautiously because of their fragile characteristics. Routine PFO closure should be reserved for prevention of recurrence when suspicion for paradoxical embolism is high. Detailed individualized decision-making is crucial before ordering PPFOC for stroke prevention in patients with cryptogenic embolism. [ABSTRACT FROM AUTHOR]

There is increasing evidence that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes an unusual pneumonia and a pro-coagulant state that significantly increases the risk of arterial and venous thromboembolism. We hypothesize that, in select patients, some complications of COVID-19 may be due to right-to-left (RTL) shunt. Shunt may be intra-pulmonary, or extra-pulmonary, and can cause paradoxical embolization, hypoxia and platypnoea orthodeoxia. Saline microbubble contrast echocardiography is a minimally invasive, inexpensive, bedside test that can detect, quantify, and define the anatomical substrate of intra-pulmonary and intra-cardiac shunts. The prevalence of patent foramen ovale (PFO) in the general population is high (20–30%) but is even higher in patients who have a stroke (50%). Thus, the striking absence of data on patients with PFO who develop COVID-19 suggests that this is being under-diagnosed. This may be because physicians and sonographers currently feel that screening for shunt is unnecessary. This could be an unintended consequence of guidance from several specialist societies to defer procedures to close PFO until after the pandemic. This may be counterproductive. Patients with shunt may be at particularly high risk of complications from COVID-19 and interventions to minimise RTL shunt could prevent paradoxical embolization and improve hypoxia in select high risk patients with COVID-19. • There is significant variation in the neurological sequelae of Coronavirus 2019 (COVID-19). • Patent foramen ovale (PFO) is present in 25-30% of the general population. • Inter-atrial defects may account for some of the heterogeneity of COVID-19 • Echocardiography with microbubble contrast should be used to screen for shunt in patients with COVID-19 • Closure of PFO may prevent paradoxical embolism and improve hypoxia in select high risk patients with COVID-19 [ABSTRACT FROM AUTHOR]

• Brain infarction is a rare complication of spontaneous intracranial hypotension (SIH). • The main mechanism is the stretching of arteries due to the sagging of the brain. • The presence of a patent foramen ovale in SIH cases is a risk factor for stroke. Spontaneous intracranial hypotension (SIH) is a rare syndrome, typically manifests as orthostatic headache. Sometimes considered as benign illness, neurological complications are well described, in particular subdural hematoma and cerebral venous sinus thrombosis. Brain infarction as complication of SIH is rarely reported. The main mechanism supported in the literature is the stretching of arteries due to the sagging of the brain. We report a case of SIH followed with brain infarction, with a distinct presentation from previous literature, suggesting a different mechanism. A 35 year-old had severe orthostatic headache, responsible for prolonged bed rest. One month later, he had acute left hemiparesis secondary to stroke and right posterior cerebral artery occlusion. Stroke MRI showed arguments for intracranial hypotension (thickened meninges). He was successfully treated with intravenous rtPA thrombolysis. Headache were resolved after an epidural blood patch. A patent foramen ovale was detected. Clinical features of this description were compared with previous literature. This case suggest a different mechanism for cerebral infarction after intracranial hypotension. In case of prolonged lying down due to intracranial hypotension, the presence of patent foramen ovale could be a risk factor for embolic stroke. [ABSTRACT FROM AUTHOR]

Background The semi-sitting position is preferred in some surgeries of the posterior fossa and the cervical spine. At the same time, it is associated with a risk of air embolism. In the presence of a patent foramen ovale (PFO) with an intracardial right-to-left shunt, an air embolism can result in a paradoxical embolism to the heart or brain. It is unclear whether the risk–benefit ratio favors the semi-sitting position in this scenario. Methods We conducted a systematic review of the relevant studies published after 2007 by searching the PubMed, Science Direct, and Cochrane Database of Systematic Reviews databases. Studies in which the presence of PFO was stated and the occurrence of paradoxical embolism was evaluated in patients who underwent neurosurgical procedures in the semi-sitting position were included in our analysis. Results We identified 4 observational studies with a total of 977 patients who underwent surgery of the posterior fossa or cervical spine in the semi-sitting position; among these, 82 had a PFO. Air embolism occurred in 33 of these 82 patients (40.2%). No paradoxical embolisms were detected. Conclusions In experienced medical centers, neurosurgery in the semi-sitting position is feasible with acceptable risk even in patients with PFO. If the PFO is large, or if a permanent right-to-left shunt is present in a patient with a history of paradoxical embolism, it may be reasonable to repair the PFO before surgery if the semi-sitting position is strongly preferred. The risk analysis must be done on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Résumé L’embolie paradoxale doit être suspectée devant une pathologie thromboembolique associée à un shunt anatomique droit–gauche. Les autres étiologies cardioemboliques doivent être éliminées surtout pour la pathologie concernée la plus fréquente qui est l’accident vasculaire cérébral. La communication interauriculaire, le foramen ovale perméable et les malformations artérioveineuses pulmonaires peuvent être responsables d’un shunt droit–gauche. La responsabilité d’un foramen ovale perméable lors de la survenue d’un accident vasculaire cérébral peut être évaluée par un score. La prévention secondaire neurologique de l’embolie paradoxale repose sur des traitements antithrombotiques et/ou interventionnels. Leur place respective commence à être mieux définie grâce à des études randomisées récentes. Paradoxical embolism should be suspected in front of a clinical phenomenon of thromboembolism associated with an anatomical right-to-left shunt. Others potential cardiac sources of thromboembolism must be ruled out. Strokes constitute the most frequent clinical manifestations of paradoxical embolism. Right-to-left left shunts are in connection with intracardiac defects (atrial septal defect and patent foramen ovale) or pulmonary arteriovenous malformations. The probability that a discovered PFO is stroke-related can be evaluated by a score. Therapeutic approaches for secondary prevention of recurrent stroke include antithrombotic and/or percutaneous treatments. The choice strategy begins to be clearer with the recent results of randomized controlled studies. [ABSTRACT FROM AUTHOR]

Introduction Systemic air embolism (SAE) is a rare but serious complication following endoscopic procedures. It may occur with or without direct vessel injury. The aim of this work is to review cases of SAE following endoscopy without proven vessel injury. Methods In this systematic review PubMed database was screened for SAE following endoscopy from 1990 to 2015. Only cases without proven major vessel injury were included in the analysis. Including one case of SAE after colonoscopy from our hospital the analysis comprised 40 cases. Results 60% of patients underwent ERCP, 33% gastroscopy and the remaining 7% other endoscopic procedures. Among patients suffering from SAE the majority had cerebral embolism (73%). In 46% of documented echocardiography a patent foramen ovale (PFO) has been confirmed as mechanism of paradoxical air embolism. Therapeutic approaches comprised most frequently hyperbaric oxygenation. In 35% of cases advanced life support was necessary whereas only 55% of patients survived SAE in total. Conclusion SAE is a serious complication of endoscopic procedures with high morbidity and mortality. In patients with present PFO high awareness should be paid to informed consent for the risk of SAE, especially stroke. Cautiousness with sedation is necessary in those patients not to delay clinical recognition of neurological SAE symptoms. [ABSTRACT FROM AUTHOR]

Abstract Loss-of-function mutations in coagulation cascade proteins lead to bleeding diasthesis. In contrast, gain-of-function mutations in these proteins, which are exceptionally rare, lead to hereditary thrombosis. This is best exemplified by Factor V (i.e., Factor V Leiden) and Factor II (i.e., p.Arg596Leu). Here, we report a family with hereditary thrombosis. The proposita presented with cerebral venous thrombosis accompanied by infarction at the age of 12 years. Despite anticoagulation therapy with oral warfarin, she later developed deep venous thrombosis in her hepatic portal veins at the age of 27 years. A medical exome analysis identified a de novo heterozygous mutation p.Tyr434His in Factor II, which was segregated within the family. A retrospective molecular diagnosis was made using a preserved surgical specimen from the proposita's mother, who had died 10 years earlier. The p.Tyr434 residue, which was substituted in the presently reported family, was located in "exosite I" of thrombin, a critical recognition site for fibrinogen, protein C, and thrombin aptamer. Therefore, the mutant thrombin likely exerted its thrombophilic effect by altering the affinity of thrombin to downstream substrates. Furthermore, the "exosite I" domain of thrombin was inhibited by the arthropod bleeding toxin Triabin (a protein discovered from the saliva of the blood-sucking triatomine bug Triatoma pallidipennis). Our observation that patients with a p.Tyr434His mutation exhibited recurrent thrombosis provides the first proof-of-concept in humans that a pharmacologic agent targeting "exosite I" could be an effective means of specifically modulating the thrombogenic-side of the coagulation system via the inhibition of factor II. [ABSTRACT FROM AUTHOR]

Abstract A 61-year-old man, admitted to our hospital for bilateral pulmonary embolism, complicated by right renal ischemia and multiple splenic infarcts due to a mobile thrombus entrapped in a patent foramen ovale, has been successfully treated with apixaban 5 mg twice daily followed by transcatheter patent foramen ovale closure. < Learning objective: Apixaban could be a therapeutic alternative to thrombolysis and surgery in patients with warfarin-resistant thrombus straddling in the patent foramen ovale (PFO). Furthermore, apixaban could be a simple and useful option to manage patients undergoing transcatheter PFO closure. Finally, in the evaluation and treatment of PFO, it is necessary to remember that it is associated not only with cryptogenic stroke but also with non-cerebral, paradoxical systemic embolic events such as myocardial infarction renal, infarct, and limb ischemia.> [ABSTRACT FROM AUTHOR]

Abstract Deep vein thrombosis occasionally causes paradoxical embolism in patients with a patent foramen ovale (PFO). We report the case of a 42-year-old female who was hospitalized for stroke. Detailed investigations revealed the existence of a PFO, pulmonary embolism, and ovarian vein thrombosis extending to inferior vena cava. She had a uterine myoma to be operated on but no other thrombophilic disorders. Anticoagulation therapy with direct oral anticoagulant successfully reduced the thrombus and prevented the recurrence of paradoxical embolism. < Learning objective: Ovarian vein thrombosis (OVT) is often associated with malignancy, pelvic surgery, or pregnancy. This case shows uterine myoma as a possible cause of OVT and demonstrates the efficacy of direct oral anticoagulant for the treatment of OVT and inferior vena cava thrombosis.> [ABSTRACT FROM AUTHOR]

Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters. [ABSTRACT FROM AUTHOR]

Introduction Cardiac phenotypes should be pronounced in hereditary hemorrhagic telangiectasia (HHT) due to frequent systemic arteriovenous malformations (AVMs), iron deficiency anemia, hypoxemia, hyperdynamic circulations, venous thromboemboli, and paradoxical emboli through pulmonary AVMs. Methods/results In an international survey, 1025 respondents (median age 55 years) met HHT diagnostic criteria: 942 (91.9%) reported nosebleeds, 452 (44.1%) at least daily. AVMs were commonly reported in pulmonary (544, 53%), hepatic (194, 18.9%) and/or cerebral (92, 9.0%) circulations. 770/1025 (75%) had used iron tablets, 256 (25.0%) intravenous iron, and 374 (36.5%) received blood transfusions. Arrhythmias were reported by 113/1025 (11%, including 44 (4.3%) with atrial fibrillation), angina by 36 (3.5%), and cardiac failure by 26 (2.5%). In multivariate logistic regression, these phenotypes were associated with hepatic AVMs/pulmonary hypertension (relatively interchangeable variables), blood transfusions, and intravenous iron. Cardiac insufficiency/failure often provokes intensive anemia treatments, but associations with arrhythmias, particularly with a greater transfusion burden, were less easy to explain. Myocardial infarction (23/1025; 2.2%), and abnormal coronary angiogram (≤ 31/76, ≤ 54%) rates appeared low. Provocative preliminary data were obtained including HHT-affected respondents' parents and grandparents in whom HHT could be confidently assigned, or excluded based on autosomal dominant inheritance patterns: in crude and survival analyses, myocardial infarctions were reported less frequently for individuals with HHT, particularly for males (p = 0.001). Conclusion Arrhythmias are the most common cardiac phenotype in HHT, and likely to be aggravated by iron deficiency anemia, its treatments, and/or high output states due to AVMs. Myocardial infarction rates may be reduced in this apparently high risk population. [ABSTRACT FROM AUTHOR]

Patients with sickle cell disease can develop acute chest syndrome and are at high risk of developing pulmonary thrombosis. We report a case of a young woman with sickle cell disease who was hospitalized for vaso-occlusive crisis and subsequently developed worsening acute chest syndrome and stroke, discovered on point of care ultrasound to have right heart failure and a thrombus straddling a patent foramen oval. POCUS is highly specific for the detection of right heart dilation/dysfunction and should be a routine component of the assessment of acutely decompensating patients. [ABSTRACT FROM AUTHOR]

Study objectives The objective was to study REM sleep macrostructure and microstructure as potential indicators of hyperarousal in insomnia by comparing good sleepers (GS) and insomnia sufferers (INS) (subdivided into psychophysiological “PSY-I” and paradoxical “PARA-I”). Design Cross-sectional comparisons of GS, PSY-I and PARA-I. Setting Participants slept for 4 consecutive nights in the laboratory where PSG was recorded. Nights 2 and 3 were combined to compare REM sleep between groups. Participants Thirty-nine PSY-I, 27 PARA-I and 47 GS completed the study, comprising home questionnaires, clinical interviews and night PSG recordings. All participants were aged between 25 and 55 and met inclusion criteria for either PSY-I, PARA-I or GS. Interventions N/A. Measurements and results Results showed no between group differences on REM sleep macrostructure. As for REM sleep microstructure, PSY-I had an increased number of wake intrusions compared to PARA-I (p = .03). Subjective SE, TST and TWT were significantly correlated with the duration of REM sleep (REMD; p ≤ .002) and with the proportion of REM sleep for PARA-I (p ≤ .06). Conclusions REM sleep macrostructure does not seem to be an adequate indicator of hyperarousal in insomnia. However, the number of wake intrusions in REM could be used to differentiate PSY-I from PARA-I and could reflect the heightened arousal of the former group. Relationships between REM sleep duration and proportion could be linked to dream imagery activity, especially in PARA-I. Further investigations are needed to identify variables that could reflect hyperarousal and differentiate insomnia types. [ABSTRACT FROM AUTHOR]

Summary The coalescence of the HIV-1 and tuberculosis (TB) epidemics in Sub-Saharan Africa has had a significant and negative impact on global health. The availability of effective antimicrobial treatment for both HIV-1 (in the form of highly active antiretroviral therapy (HAART)) and TB (with antimycobacterial agents) has the potential to mitigate the associated morbidity and mortality. However, the use of both HAART and antimycobacterial therapy is associated with the development of inflammatory paradoxical syndromes after commencement of therapy. These include paradoxical reactions (PR) and immune reconstitution inflammatory syndromes (IRIS), conditions that complicate mycobacterial disease in HIV seronegative and seropositive individuals. Here, we discuss case definitions for PR and IRIS, and explore how advances in identifying the risk factors and immunopathogenesis of these conditions informs our understanding of their shared underlying pathogenesis. We propose that both PR and IRIS are characterized by the triggering of exaggerated inflammation in a setting of immunocompromise and antigen loading, via the reversal of immunosuppression by HAART and/or antimycobacterials. Further understanding of the molecular basis of this pathogenesis may pave the way for effective immunotherapies for the treatment of PR and IRIS. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to contribute to the discussion of differential diagnosis in paradoxical vocal fold movement (PVFM), a disorder frequently associated with episodes of breathing difficulty and stridor. Because of analogous respiratory symptoms, PVFM is often misdiagnosed as asthma. Additional evidence suggests the association of factors such as respiratory struggle during physical exertion, digestive reflux, and respiratory allergies with PVFM, particularly in athletes and young females. Interdisciplinary attention is warranted to avoid unnecessary utilization of medical resources and potential delay in the application of proper treatment. Methods A description of critical points in PVFM differential diagnosis is proposed, featuring the assessment of a seven-year-old female with a history of behaviors considered to exacerbate voice fatigue symptoms. Noticeably, the child has consistently demonstrated tiredness and respiratory difficulties during physical education classes. Past use of oral steroids to reduce respiratory problems was applied with no improvement; short-acting beta 2-agonists have been also tried with mild improvement. Indications of instability and effort associated with respiratory–phonatory functions were demonstrated. Furthermore, there was evidence of GERD and seasonal allergies. Results The literature suggests an association of factors such as respiratory struggle during physical exertion, unwanted vocal effort, GERD, and respiratory allergies in individuals with PVFM, particularly in young females. A diagnosis of PVFM was suggested, in association with paradoxical vocal folds motion caused by respiratory difficulties verified by laryngeal examination. Conclusions In PVFM, the vocal folds adduct during inhalation, thereby restricting the airway opening. Inconsistent vocal folds movement during phonation may also lead to PVFM symptoms. Acute bronchospasm/asthma-like symptoms, as well as additional morbidity may impact accuracy of diagnosis, leading to unnecessary use of asthma medications and office/emergency room consultations. [ABSTRACT FROM AUTHOR]

The neuropeptide S (NPS) system is characterized by a unique pharmacology because it has anxiolytic-like effects and promotes arousal and wakefulness. To shed light on this peptidergic system, we tested the sedative effect of the central depressants diazepam and ethanol on the loss of righting reflex in mice lacking the neuropeptide S receptor (NPSR), NPSR(−/−). Furthermore, we tested the effect of the intracerebroventricular (ICV) administration of NPS on the sedative effect of diazepam and ethanol in NPSR(−/−) and their wild type counterpart NPSR(+/+). Finally, we evaluated the effect of the pro-arousal neuropeptides CRF and Hcrt-1/Ox-A in NPSR-deficient mice. Contrary to our expectations, the results showed that the NPSR(−/−) were less sensitive to the hypnotic effects of both diazepam and ethanol compared with their wild type littermates. ICV NPS was able to attenuate the sedative effect of both alcohol and diazepam in wild type mice, but not in the NPSR(−/−) line. The administration of CRF and Hcrt-1/Ox-A, two classic pro-arousal peptides, elicited the same effects in both NPSR(−/−) and wild type mice, ruling out the possibility that adaptive mechanisms occurring at the level of these two systems could have occurred during NPSR(−/−) development to compensate for the lack of NPSR receptors. Our findings demonstrated that the deletion of NPSR leads to minor changes in the arousal behavior of mice. Moreover, we demonstrated that the deletion of NPSR did not lead to compensatory changes in the vigilance-promoting effects of the CRF and Hcrt-1/Ox-A systems. [ABSTRACT FROM AUTHOR]

Background Anticoagulants stimulate fibrinolysis in vitro, mainly by inhibiting thrombin-mediated TAFI activation. Surprisingly, however, direct thrombin inhibitors (DTIs) inhibit fibrinolysis and enhance thrombin generation in vitro when tested in the presence of high thrombomodulin (TM) concentrations. Because the paradoxical effect on thrombin generation was shown to be protein C (PC)-dependent, we investigated the role of PC in the antifibrinolytic effect of two DTIs, dabigatran and argatroban. Methods and Results In the presence of 10 nM TM, both dabigatran (0.5μM) and argatroban (1μM) prolonged clot lysis time and enhanced thrombin generation. This notwithstanding, the DTIs inhibited thrombin-mediated TAFI activation, peak TAFIa activity being reduced by 60%. A specific feature of TAFI activation curve in the presence of DTIs was a much slower disappearance of TAFIa activity, which was likely the cause of fibrinolysis inhibition. The addition of an anti-PC antibody (αPC) nullified the paradoxical effect of DTIs on thrombin generation but influenced neither TAFI activation nor the fibrinolysis time. Conclusions Our results suggest that the inhibition of PC activation by DTIs in the presence of TM, while enhancing thrombin generation, has no effect on thrombin-mediated TAFI activation. The inhibition of fibrinolysis by DTIs can be explained by the prolonged activation of TAFI resulting from the sustained release of thrombin from thrombin-DTI complex. While the clinical relevance of these findings needs to be investigated by in vivo studies, our data might help understanding the role of the different players in the regulation of thrombin generation, TAFI activation and fibrinolysis resistance. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between arterial stiffness and stroke severity and in-hospital outcome in patients admitted with acute ischemic stroke. Methods We prospectively studied 415 consecutive patients who were admitted with acute ischemic stroke (39.5% males, age 78.8 ± 6.6 years). On the third day of hospitalization, the following markers of arterial stiffness were recorded: central systolic blood pressure (cSBP), diastolic BP (cDBP), mean pressure (cMP), pulse pressure (cPP), augmentation index (AIx) and pulse wave velocity (PWV). The severity of stroke was assessed on admission with the National Institutes of Health Stroke Scale (NIHSS) score. The outcome was evaluated with rates of dependency at discharge (modified Rankin scale score between 2 and 5) and in-hospital mortality. Results None of the markers of arterial stiffness showed significant correlation with the NIHSS score on admission. However, there was a trend for an inverse correlation with AIx (r = -0.142, p = 0.064) and for a positive correlation with PWV (r = 0.235, p = 0.054). None of the markers of arterial stiffness differed between patients who were dependent at discharge and those who were independent. Patients who died during hospitalization had higher cDBP and cMP but lower cPP and AIx than patients who were discharged. In binary logistic regression analysis, independent predictors of in-hospital mortality were NIHSS score on admission (relative risk (RR) 1.16, 95% confidence interval (CI) 1.08-1.25, p < 0.001), presence of atrial fibrillation (RR 6.41, 95% CI 1.37-29.93, p = 0.018) and AIx (RR 0.94, 95% CI 0.89-0.99, p = 0.030). Conclusions Increased AIx appears to be associated with lower in-hospital mortality rates in elderly patients with acute ischemic stroke. Other markers of arterial stiffness do not appear to be associated with short-term outcome in this population. [ABSTRACT FROM AUTHOR]

Paradoxical embolism is an important clinical entity among patients with venous thromboembolism in the presence of intracardiac or pulmonary shunts. The clinical presentation is diverse and potentially life-threatening. Although the serious nature and complications of paradoxical embolism are recognized, the disease entity is still rarely considered and remains under-reported. This paper provides an overview on the different clinical manifestations of paradoxical embolism, describes the diagnostic tools for the detection of intracardiac and pulmonary shunts, reviews therapeutic options, and summarizes guideline recommendations for the secondary prevention of paradoxical embolism. [ABSTRACT FROM AUTHOR]

Abstract: We investigated how salt crystallization inside a porous building material influences the formation of a receding drying front. Nuclear Magnetic Resonance (NMR) is used to measure non-destructively both hydrogen and dissolved sodium ions during drying process. In this study, we focused on the influence of NaCl on the drying behavior of porous media. The results show that salt changes the drying behavior. At low relative humidities (RH~0%), the drying rate of a brick saturated with NaCl solution is much lower than the drying rate of water saturated brick. Moreover, the presence of salt suppresses the development of a receding front. In this case homogenous drying of the material continues till very low saturation values. This is due to salt crystallization near the surface of the brick that causes blockage of the pores. This blockage reduces evaporation rate at the surface and allows maintaining a continuous hydraulic connection between the surface of the porous medium and the liquid present inside the material till low saturation values. In the case of a salt solution saturated brick, increasing relative humidity to 55% and 70% leads to a paradoxical situation where the evaporation rate is greater for 55% and 70% RH than for 0% RH. The paradox is explained by the impact of evaporation rate on the efflorescence microstructure, leading to the formation of a blocking crust for sufficiently high evaporation rates and non-blocking efflorescence for sufficiently low evaporation rates. The fundamental difference between the two types of efflorescence is demonstrated from a simple imbibition experiment. Using a simple continuum scale model of drying, critical moisture content was determined and all the essential features of the experimental results are validated. It is shown that critical moisture content can be very low in the case of fired-clay brick due to the low threshold of the pore space, which is consistent with the relatively large pore size distribution of the fired-clay brick. [Copyright &y& Elsevier]

Résumé: Cette observation rapporte la découverte d’embolies coronaires d’origine paradoxale secondaires à un thrombus adhérent de l’oreillette droite par un foramen ovale perméable (FOP). Un patient de 64ans, avec antécédent d’insuffisance mitrale non suivie, est hospitalisé pour un tableau de détresse respiratoire aiguë révélant une insuffisance mitrale (IM) par rupture de cordage et une embolie pulmonaire. La coronarographie réalisée dans le cadre du bilan de l’IM retrouve deux images typiques d’embolies coronaires avec un réseau non athéromateux. Le patient bénéficie d’un remplacement valvulaire mitral. À la mise en place de la circulation extracorporelle, est découvert un thrombus adhérent fibrino-cruorique de l’oreillette droite et un FOP. L’étude des valves ne retrouve pas d’argument pour une endocardite infectieuse. Un scanner cérébral réalisé devant l’absence de réveil met en évidence plusieurs infarctus cérébraux. On retient l’hypothèse d’embolies coronariennes d’origine paradoxale devant l’association d’un thrombus adhérent de l’oreillette droite, d’une embolie pulmonaire et d’embolies systémiques, coronaires et cérébrales avec un FOP. Les embolies coronaires sont rares. On retient trois principales causes : l’origine iatrogène le plus souvent, les causes directes par micro-emboles provenant surtout d’endocardites infectieuses et les embolies d’origine paradoxale. Il existe deux types de thrombus de l’oreillette droite, les thrombus mobiles, les plus fréquents, provenant du système veineux périphérique et les thrombus adhérents, se constituant in situ et rares. Les embolies coronaires d’origine paradoxale représentent une faible proportion des étiologies des embolies coronaires. Néanmoins, ce diagnostic doit être évoqué en l’absence de cause iatrogène ou infectieuse. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to examine the frequency of indications for and the immediate and long-term clinical outcomes of transcatheter closure of patent foramen ovale (PFO). Background: Transcatheter PFO closure is commonly performed for several indications, including cryptogenic stroke, despite conflicting data regarding the efficacy of this intervention. Methods: We report the outcomes of 800 consecutive patients (52% male, 50 ± 14 years of age) who underwent PFO closure at our institution after multidisciplinary evaluation over a 16-year period. Results: Indications for closure included cryptogenic cerebrovascular event (94%), hypoxemia (2%), peripheral embolism (3%), and migraine headaches (2%). Procedural success was 99% with effective closure obtained in 93% of patients. At a mean follow-up of 42.7 ± 33.4 months, 21 patients suffered a recurrent ischemic neurologic event (12 strokes, and 9 transient ischemic attacks) for an incidence rate of 0.79 events per 100 person-years and freedom from recurrent events of 91.6% at 10 years. There was no device-based difference in the rate of recurrent ischemic neurologic events (p = 0.82). Only Eustachian valve prominence (hazard ratio: 9.04; 95% confidence interval: 2.07 to 39.44; p = 0.0034) was associated with recurrent neurologic events. Conclusions: Transcatheter PFO closure is safe and feasible in patients with several clinical indications. The long-term efficacy of this intervention in patients with paradoxical embolism appears superb in this observational study. Carefully selected patients with features suggestive of paradoxical embolism are the most likely to benefit from PFO closure and should be the focus of future investigation. [Copyright &y& Elsevier]

Abstract: Background/objectives: This study aims to assess whether patent foramen ovale (PFO) closure is superior to medical therapy in preventing recurrence of cryptogenic ischemic stroke or transient ischemic attack (TIA). Methods: We searched PubMed for randomized trials which compared PFO closure with medical therapy in cryptogenic stroke/TIA using the items: “stroke or cerebrovascular accident or TIA” and “patent foramen ovale or paradoxical embolism” and “trial or study”. Results: Among 650 potentially eligible articles, 3 were included including 2303 patients. There was no statistically significant difference between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs. 2.94% respectively, OR: 0.64, 95%CI: 0.37–1.10), TIA (2.08% vs. 2.42% respectively, OR: 0.87, 95%CI: 0.50–1.51) and death (0.60% vs. 0.86% respectively, OR: 0.71, 95%CI: 0.28–1.82). In subgroup analysis, there was significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs. medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21–0.98, relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to-treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy, OR: 0.93, 95%CI: 0.45–2.11). Compared to medical therapy, the number of patients with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60–5.42) but higher in the STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47–27.84). Conclusions: This meta-analysis does not support PFO closure for secondary prevention with unselected devices in cryptogenic stroke/TIA. In subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset AF, however. This observation should be confirmed in further trials using inclusion criteria for patients with high likelihood of PFO-related stroke recurrence. [Copyright &y& Elsevier]

Abstract: Objectives: To investigate the role of collateral venous pathways between the left brachiocephalic vein (LBV) and the left atrium through an arcade comprising the left superior intercostal vein (LSICV), left vertical vein (LVV), and pulmonary veins as a potential cause of paradoxical embolism. Methods: A retrospective search was performed to find symptomatic patients with negative work up for paradoxical emboli whose chest CT or MR angiography by left arm contrast injection showed a visible right to left shunt through the LSICV/LVV collateral pathway (symptomatic group). We also evaluated the characteristics of this collateral pathway in 150 chest CT angiographies from general referrals (comparison group). Results: We found 7 symptomatic patients. Initial presentations included neurological symptoms in all patients and episodes of hypoxemia in three patients. Communications between the LBV and left atrium through the LSICV/LVV pathway was seen is all 7 cases and confirmed by transesophageal echocardiography in two. An abnormal LBV was seen in 6 cases (absence in one, stenosis in 5). Moderate superior vena cava stenosis was seen in one and acute right subclavian vein thrombosis in one. Six patients had past history of an upper extremity central line placement. In the comparison group, LSICV was seen in 73 (48%), connecting to the hemiazygos vein in 41, to a LVV in 19 and to the left atrium in 7. Conclusion: LSICV/LVV collaterals are common and can be a potential route for paradoxical emboli especially when stenosis of a draining vein such as LBV exists. [Copyright &y& Elsevier]

Abstract: Patent foramen ovale (PFO), a common congenital cardiac abnormality, is a connection between the right and left atria in the heart. As a “back door to the brain”, PFO can serve as a conduit for paradoxical embolism, allowing venous thrombi to enter the arterial circulation, avoiding filtration by the lungs, and causing ischemic stroke. PFO-related strokes affect more than 150,000 people per year in the US, and PFO is present in up to 60% of migraine patients with aura, and in one out of four normal individuals. So, in such a highly prevalent condition, what are the best treatment and prevention strategies? Emerging studies show PFO-related neurovascular disease to be a multi-organ condition with varying individual risk factors that may require individualized therapeutic approaches — opening the field for new pharmacologic and therapeutic targets. The anatomy of PFO suggests that, in addition to thrombi, it can also allow harmful circulatory factors to travel directly from the venous to the arterial circulation, a concept important in finding novel therapeutic targets for PFO-related neurovascular injury. Here, we: 1) review emerging data on PFO-related injuries and clinical trials; 2) discuss potential mechanisms of PFO-related neurovascular disease in the context of multi-organ interaction and heart-brain signaling; and 3) discuss novel therapeutic targets and research frontiers. Clinical studies and molecular mapping of the circulatory landscape of this multi-organ disease will both be necessary in order to better individualize clinical treatment for a condition affecting more than a quarter of the world's population. [Copyright &y& Elsevier]

Abstract: Species distributions reflect limiting factors, particularly near the margins of their range where density and abundance decrease as environmental factors decrease or increase to non-optimal conditions. I test whether the keystone saguaro cactus (Carnegiea gigantea), a shallow-rooted species, is indeed distributed disproportionately in areas of concentrated drainage (runnels) in a water-limited population. Carnegiea and a common nurse were sampled at a marginal site in and out of areas with concentrated surface water and chi-square analysis was used to determine the pattern of distribution. In this study I found that, surprisingly, near the hot, water-limited edge of their range, C. gigantea are found significantly less often in areas where more water would be available to them. For example, while only 20% of nurses were on interfluves, half of Carnegiea protégé were there. One possible explanation is that the subsequent redistribution of seeds by water away from preferred microsites may be important in shaping the final pattern of successful establishment. The shallow-rooted Carnegiea relies entirely on surface water for its moisture; it is thus paradoxical that the surface water so fundamentally essential to its survival throughout its life appears to hinder its establishment in precisely those sites where the greatest surface water would be available, particularly near the water-limited edge of its range. [Copyright &y& Elsevier]

Abstract: Lethal embolic events in children are an uncommon occurrence that may be first detected at autopsy. Emboli consist of thrombi, tumours, infective organisms, fat, air and foreign body material. The most significant circulations that may be obstructed are the pulmonary, coronary and cerebral. Rare conditions such as arteriovenous malformations may act as sources for emboli in children, and the brain is at particular risk from paradoxical embolism. The latter is facilitated by right to left communications in the heart such as atrial and ventricular septal defects and also from pulmonary vascular abnormalities such as hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) and arteriovenous fistulas. Iatrogenic causes of thromboembolism must be considered in children with indwelling central venous catheters and ventriculoatrial shunts. Although rare, embolic events do occur in children with lethal consequences. As the incidence of embolization in clinical settings has been increasing, due to improved survival of children with predisposing chronic conditions, it is likely that more of these cases will be the subject of forensic evaluation. [Copyright &y& Elsevier]

Summary: Paradoxical embolism is a possible cause of ischemic stroke, particularly in younger patients without any other cause, i.e. cryptogenic stroke, and a patent foramen ovale is the most frequently assumed cause. The contrast transcranial Doppler monitoring mode has a sensitivity that is comparable to contrast transesophageal echocardiography for detection of a right-to-left shunt, however, the contrast transesophageal echocardiography remains the “golden standard” for the detection of a patent foramen ovale. Diagnostic studies that can identify a patent foramen ovale may be considered for prognostic purposes. In most cases, however, it is difficult to establish a firm etiological association and the debate about medical or interventional management is ongoing. Other possible causes of right-to-left shunting leading to cerebral complications like pulmonary arteriovenous malformations have also been noted but are rarely discussed. [ABSTRACT FROM AUTHOR]

Objectives: In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO). Background: A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO. Methods: We conducted a MEDLINE search with standard search terms to determine eligible studies. Results: Adjusted incidence rates of RNE were 0.8 (95% confidence interval [CI]: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia. Conclusions: Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies. [ABSTRACT FROM AUTHOR]

A 72 year-old woman was admitted with a one-week history of weakness, right limb pain and progressive breathlessness. Her blood pressure was 60/40mmHg, ECG showed inverted T waves in the precordial leads and incomplete right bundle branch block (RBBB). Transthoracic echocardiography revealed a large serpentine mobile mass across the atrial septum and mitrale valve extending into the left ventricular cavity. The right ventricle was dilated and peak systolic tricuspid annular velocity (RV-Sm) was 6.5cm/sn, indicate right ventricular systolic function was severely depressed. Transoesophageal echocardiography showed a large, mobile thrombus in the foramen ovale, extending into the left atrium and ventricle. As the patient was in a haemodynamically compromised condition, high dose rapid infusion of streptokinase was administered. However, the thrombus did not fully resolve with this intervention. Therefore, low dose continuous streptokinase infusion was administered for an additional 72h resulting in full resolution of the lesion by the third day of therapy. The optimal management of impending paradoxical embolism remains unclear. Prolonged continuous thrombolytic infusion may be a option for patients who do not experience full resolution of high risk thrombi with conventional thrombolytic therapy. [Copyright &y& Elsevier]