Patients who had had a cryptogenic stroke and had a PFO were randomly assigned to medical therapy or PFO closure. At a median of 5.9 years, the rate of recurrent ischemic strokes was lower in the PFO ...closure group than in the medical-therapy group.
Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals ...with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.
Bariatric surgery is the most effective available treatment for obesity. The most frequently performed operation, Roux-en-Y gastric bypass (RYGB), causes profound weight loss and ameliorates ...obesity-related comorbid conditions, especially type 2 diabetes mellitus (T2DM). Approximately 84% of diabetic patients experience complete remission of T2DM after undergoing RYGB, often before significant weight reduction. The rapid time course and disproportional degree of T2DM improvement after RYGB compared with equivalent weight loss from other interventions suggest surgery-specific, weight-independent effects on glucose homeostasis. Potential mechanisms underlying the direct antidiabetic impact of RYGB include enhanced nutrient stimulation of lower intestinal hormones (e.g. glucagon-like peptide-1), altered physiology from excluding ingested nutrients from the upper intestine, compromised ghrelin secretion, modulations of intestinal nutrient sensing and regulation of insulin sensitivity, and other changes yet to be fully characterized. Research aimed at determining the relative importance of these effects and identifying additional mechanisms promises not only to improve surgical design but also to identify novel targets for diabetes medications.
Roux-en-Y gastric bypass causes complete remission of T2DM in a large majority of cases; mounting evidence indicates that this remarkable phenomenon results from effects beyond those related to reduced food intake and body weight.
IMPORTANCE: Patent foramen ovale (PFO)–associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, ...the best treatment for any individual is often unclear. OBJECTIVE: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. DESIGN, SETTING, AND PARTICIPANTS: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. EXPOSURES: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. MAIN OUTCOMES AND MEASURES: Ischemic stroke. RESULTS: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio HR, 0.41 95% CI, 0.28-0.60). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was −0.7% (95% CI, −4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, −0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. CONCLUSIONS AND RELEVANCE: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.
Despite the diffusion into practice of percutaneous closure of a patent foramen ovale (PFO) in patients with cryptogenic stroke (CS), the benefits have not been demonstrated, and remain unclear. For ...any individual presenting with a PFO in the setting of CS, it is not clear whether the PFO is pathogenically-related to the index event or an incidental finding. Further, the overall rate of stroke recurrence is low in patients with CS and PFO. How patient-specific factors affect the likelihood that a discovered PFO is related to an index stroke or affect the risk of recurrence is not well understood. These probabilities are likely to be important determinants of the benefits of PFO closure in CS.
The goal of the Risk of Paradoxical Embolism (RoPE) Study is to develop and test a set of predictive models that can identify those patients most likely to benefit from preventive treatments for PFO-related stroke recurrence, such as PFO closure. To do this, we will construct a database of patients with CS, both with and without PFO, by combining existing cohort studies. We will use this pooled database to identify patient characteristics associated with the presence (versus the absence) of a PFO, and to use this "PFO propensity" to estimate the patient-specific probability that a PFO was pathogenically related to the index stroke (Model #1). We will also develop, among patients with both a CS and a PFO, a predictive model to estimate patient-specific stroke recurrence risk based on clinical, radiographic and echocardiographic characteristics. (Model #2). We will then combine Models #1 and #2 into a composite index that can rank patients with CS and PFO by their conditional probability that their PFO was pathogenically related to the index stroke and the risk of stroke recurrence. Finally, we will apply this composite index to completed clinical trials (currently on-going) testing endovascular PFO closure against medical therapy, to stratify patients from low-expected-benefit to high-expected-benefit.
In this study, closure of a patent foramen ovale versus medical therapy alone after cryptogenic stroke was not effective in preventing recurrent stroke. Secondary analyses suggested a possible ...benefit, but the study did not permit a definitive conclusion.
It is unknown whether closure of a patent foramen ovale is effective in the prevention of recurrent stroke after a cryptogenic ischemic stroke. Observational studies and meta-analyses have suggested that closure is associated with a benefit; however, a randomized trial, Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale (CLOSURE I), failed to show the superiority of closure over medical therapy alone.
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In observational studies, the Amplatzer PFO Occluder has been shown to have advantageous safety features as a closure device.
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Bariatric surgery is the most effective available treatment for obesity. The most frequently performed operation, Roux-en-Y gastric bypass (RYGB), causes profound weight loss and ameliorates ...obesity-related comorbid conditions, especially type 2 diabetes mellitus (T2DM). Approximately 84% of diabetic patients experience complete remission of T2DM after undergoing RYGB, often before significant weight reduction. The rapid time course and disproportional degree of T2DM improvement after RYGB compared with equivalent weight loss from other interventions suggest surgery-specific, weight-independent effects on glucose homeostasis. Potential mechanisms underlying the direct antidiabetic impact of RYGB include enhanced nutrient stimulation of lower intestinal hormones (e.g. glucagon-like peptide-1), altered physiology from excluding ingested nutrients from the upper intestine, compromised ghrelin secretion, modulations of intestinal nutrient sensing and regulation of insulin sensitivity, and other changes yet to be fully characterized. Research aimed at determining the relative importance of these effects and identifying additional mechanisms promises not only to improve surgical design but also to identify novel targets for diabetes medications.
Patent foramen ovale (PFO) is significantly associated with cryptogenic stroke (CS). However, even in patients with CS, a PFO can be an incidental finding. We sought to estimate the probability that ...a PFO in a patient with CS is incidental.
A systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus control subjects with stroke of known cause. Using simple assumptions and Bayes' theorem, we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus control subjects in different age populations, with or without atrial septal aneurysms, and were used to summarize across studies the probability that a PFO in CS is incidental.
The summary OR (95% CIs) for PFO in CS versus control subjects was 2.9 (CI, 2.1 to 4.0). The corresponding ORs for young and old patients (< or >or=55 years) were 5.1 (3.3 to 7.8) and 2.0 (>1.0 to 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28% to 39%) in age-inclusive studies, 20% (16% to 25%) in younger patients, and 48% (34% to 66%) in older patients. These probabilities were much lower when an atrial septal aneurysm was present.
In patients with otherwise CS, approximately one third of discovered PFOs are likely to be incidental and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an atrial septal aneurysm, suggesting the importance of patient selection in therapeutic decision-making.
Although the prevalence of a patent foramen ovale (PFO) in the general population is ≈25%, it is approximately doubled among cryptogenic stroke (CS) patients. This has generally been attributed to ...paradoxical embolism, and many physicians recommend PFO closure to prevent recurrence. However, the benefit of PFO closure in patients with stroke has not been demonstrated. Furthermore, the epidemiology of stroke recurrence in patients with CS with PFO versus without PFO and in those with large right-to-left shunts versus small right-to-left shunts has yielded results that appear difficult to reconcile with the hypothesis that paradoxical embolism is an important cause of stroke recurrence. The purpose of this review is to critically examine the epidemiologic evidence that PFO is a potentially modifiable risk factor for stroke recurrence in patients with CS. The evidence suggests that many patients with CS and PFO have strokes that are PFO attributable, but many have strokes that are unrelated to their PFO. We introduce the concept of "PFO propensity," defined as the patient-specific probability of finding a PFO in a patient with CS on the basis of age and other risk factors. We show that this value is directly related to the probability that CS is PFO attributable. Because there is substantial heterogeneity in both PFO propensity and recurrence risk among patients with PFO and CS, stratification for PFO closure by these joint probabilities will likely prove crucial for appropriate patient selection.
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