Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.

BACKGROUND: Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS: In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS: A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS: Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).

Five-Year Clinical Outcome and Valve Durability After Transcatheter Aortic Valve Replacement in High-Risk Patients.

BACKGROUND: The FRANCE-2 registry (French Aortic National Corevalve and Edwards) previously reported good early- and medium-term clinical and echocardiographic efficacy for transcatheter aortic valve replacement. We here report 5-year follow-up results from the registry. METHODS: The registry includes all consecutive patients undergoing transcatheter aortic valve replacement for severe aortic stenosis in France. Follow-up is scheduled at 30 days, 6 months, then annually from 1 to 5 years. Clinical events were defined according to the Valve Academic Research Consortium criteria, and hemodynamic structural valve deterioration (SVD) was defined according to the consensus statement by the European Association of Percutaneous Cardiovascular Interventions. RESULTS: Between January 2010 and January 2012, 4201 patients were enrolled in 34 centers. Five-year vital status was available for 95.5% of patients; 88.1% had clinical evaluation or died. Overall, at 5 years, all-cause mortality was 60.8% (n=2478; 95% CI, 59.3% to 62.3%). The majority of cardiovascular events occurred in the first month after valve implantation, and incidence remained low thereafter, at <2% per year up to 5 years, except for heart failure. The rate of heart failure was 14.3% at 1 year, then decreased over time to <5% per year. In cumulative incidence function, the rates of severe SVD and moderate/severe SVD at 5 years were 2.5% and 13.3%, respectively. Mortality did not differ between patients with or without severe SVD (hazard ratio, 0.71; 95% CI, 0.47-1.07; P=0.1). Finally, in the population of patients with severe SVD, 1 patient (1.7%) experienced a stroke, and 8 patients presented ≥1 heart failure event (13.3%). CONCLUSIONS: The 5-year follow-up results of the FRANCE-2 registry represent the largest long-term data set available in a high-risk population. In surviving patients, the low rate of clinical events and the low level of SVD after 1 year support the long-term efficacy of transcatheter aortic valve replacement in both types of transcatheter prosthesis featuring in the registry.

Rapid pacing using the left ventricular guidewire: Reviving an old technique to simplify BAV and TAVI procedures.

OBJECTIVES: We sought to demonstrate the safety and efficacy of rapid left ventricular (LV) pacing through the guidewire during balloon aortic valvuloplasty (BAV) and Transaortic valve implantation (TAVI). BACKGROUND: Right ventricular temporary pacing during TAVI and BAV is time-consuming and associated with vascular and pericardial complications. METHODS: Rapid left ventricular pacing was provided via the back-up 0.035″ guidewire. The cathode of an external pacemaker was placed on the tip of the 0.035″ wire and the anode on a needle inserted into the groin. Insulation was ensured by the balloon or TAVI catheter. RESULTS: 38 BAV and 87 TAVI procedures were performed in 113 consecutive patients in three centers with one for one pacing (160-200 bpm) in all patients. A significant reduction in blood pressure was achieved with a mean systolic pressure of 44 mm Hg during stimulation. Mean procedural time was 49.7 ± 31 min for BAV and 68.7 ± 30.9 for TAVI. A temporary venous pacemaker was required in 12 patients; only 12% of TAVI patients had a femoral central venous catheter. Femoral venous puncture was not performed in BAV patients. No venous vascular complications were observed. One case of successfully treated tamponade (0.8%) occurred 8 hr post procedure. In-hospital mortality rates were 4.6% and 2.6% in the TAVI and BAV groups, respectively. CONCLUSIONS: Use of the LV guidewire for rapid pacing during BAV and TAVI was shown to be simple, reproducible, and prevented complications associated with RV temporary leads thus potentially simplifying TAVI and enhancing its safety. © 2016 Wiley Periodicals, Inc.

Registry of transcatheter aortic-valve implantation in high-risk patients.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. METHODS: All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause. RESULTS: A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival. CONCLUSIONS: This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).

Prognostic significance of severe coronary microvascular dysfunction post-PCI in patients with STEMI: A systematic review and meta-analysis.

Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagnosis of severe CMVD after primary percutaneous coronary intervention (pPCI). However, these indexes are not routinely assessed in STEMI patients. Our main objective was to clarify the association between IMR or HMR and long-term major adverse cardiovascular events (MACE), through a systematic review and meta-analysis of observational studies. We searched Medline, PubMed, and Google Scholar for studies published in English until December 2020. The primary outcome was a composite of cardiovascular death, non-cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalization for heart failure occurring after at least 6 months following CMVD assessment. We identified 6 studies, reporting outcomes in 1094 patients (mean age 59.7 ± 11.4 years; 18.2% of patients were women) followed-up from 6 months to 7 years. Severe CMVD, defined as IMR > 40 mmHg or HMR > 3mmHg/cm/sec was associated with MACE with a pooled HR of 3.42 [2.45; 4.79]. Severe CMVD is associated with an increased risk of long-term adverse cardiovascular events in patients with STEMI. Our results suggest that IMR and HMR are useful for the early identification of severe CMVD in patients with STEMI after PCI, and represent powerful prognostic assessments as well as new therapeutic targets for clinical intervention.

Actual concepts in rhinosinusitis: a review of clinical presentations, inflammatory pathways, cytokine profiles, remodeling, and management.

Rhinosinusitis (RS) is a heterogeneous group of diseases. It is a significant and increasing health problem that affects about 15% of the population in Western countries. It has a substantial impact on patients' health-related quality of life and daily functioning and represents a huge financial burden to society and the health care system as a result of the direct and indirect costs. In addition, RS is not well-understood, and little is known about the etiology and pathophysiology. In the past decade, many papers have been published that have changed our understanding of RS. RS is commonly classified into acute and chronic RS based on symptom duration. In acute RS, an inflammatory reaction initiated by a viral infection characterizes most uncomplicated, mild to moderate cases. Therefore, the first line of treatment for these cases are intranasal steroids and not antibiotics. In severe and complicated cases, antibiotics combined with topical steroids remain the treatment of choice. On the other hand, chronic RS is actually subdivided into two distinct entities (chronic rhinosinusitis with and without polyps), as growing evidence indicates that these entities have specific inflammatory pathways and cytokine profiles. The authors review recent data regarding the clinical presentations, cytokine profiles, tissue remodeling, and modalities of treatment for each form of RS.

TAVR Patients Requiring Anticoagulation: Direct Oral Anticoagulant or Vitamin K Antagonist?

OBJECTIVES: Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). BACKGROUND: The choice of optimal drug for anticoagulation after TAVR remains debated. METHODS: Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety). RESULTS: A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P < 0.005) and major bleeding including hemorrhagic stroke (HR: 1.64; 95% CI: 1.17-2.29; P < 0.005) were lower in patients on DOACs compared with those on VKAs. The rates of ischemic stroke (HR: 1.32; 95% CI: 0.81-2.15; P = 0.27) and acute coronary syndrome (HR: 1.17; 95% CI: 0.68-1.99; P = 0.57) did not differ among groups. CONCLUSIONS: In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Understanding Pathophysiological Concepts Leading to Obstructive Apnea.

Obstructive sleep apnea (OSA) results from a combination of several factors leading to the obstruction of the upper respiratory tract (URT). OSA represents a systemic pathophysiological entity and leads to many comorbidities such as hypertension, coronary ischemia, and stroke. Patients with this pathophysiological entity experience also an increased risk of postoperative complications. Obesity is certainly the main cause of developing OSA. However, many other predisposing factors influence the genesis of obstructive apnea. It is important to understand the complexity of the interactions between predisposing factors to understand the relationship between weight loss following obesity surgery and the improvement in the severity of OSA. In this narrative review, we expose the seven major categories of predisposing factors that interact to generate obstructive apneas in patients, namely the anatomic abnormalities of the URT, the mechanical and the metabolic responses of the upper airway musculature, the loop gain, the arousal threshold, and the hormonal abnormalities. The genesis of apnea is the result of a complex dynamic interaction between the anatomical risk factors and the compensatory neuromuscular reflexes. All of these points are integrally part of the perioperative care of the obese patients. Finally, we will discuss different options for weight reduction.

Clinical significance of olfactory event-related potentials related to orthonasal and retronasal olfactory testing.

OBJECTIVE: The purpose of this study was to evaluate the likelihood of recording olfactory event-related potentials (OERPs) in patients with an olfactory dysfunction and to correlate the electrophysiological responses to orthonasal and retronasal olfactory testing. DESIGN/MATERIALS AND METHODS: This was a prospective study of 65 patients with different origins of their olfactory loss. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test (orthonasal score; maximal score 48) and retronasal olfactory function with odorized powders presented intraorally (retronasal score; maximal score 20). The OERPs were obtained after presentation of 2-phenyl ethyl alcohol, the selected olfactory stimulus. Causes of olfactory dysfunction included postinfectious olfactory loss (n = 15), head trauma (n = 26), nasal polyposis (n = 15), and mixed causes (idiopathic, toxic, drug induced) (n = 9). RESULTS: Based on orthonasal testing, 32 and 33 patients were diagnosed with anosmia and hyposmia, respectively. Twenty-two patients from the hyposmic group demonstrated reliable OERPs. No OERPs were recorded in the anosmic group. Prevalence of OERPs in a cohort of patients with olfactory dysfunction was 33.8% (22 of 65). Median score (expressed as the percentage of the maximal score that could be obtained theoretically) in which OERPs were recorded was 50% (24 of 48) with orthonasal testing and 80% (16 of 20) with retronasal testing. CONCLUSIONS: Patients with olfactory dysfunction usually demonstrate OERPs in one third of the cases. When olfactory dysfunction is in the range that separates normosmic subjects from anosmic patients, patients may have identifiable OERPs. Interpretation of both orthonasal and retronasal psychophysical olfactory testing should be supported by the recording of OERPs in a clinical setting.

Evaluation of Imaging Strategy to Optimize and Improve Outcome of Transcatheter Aortic Valvular Implantation.

Cardiac computed tomography (CT) provides additional information with ultrasound in the transcatheter heart valve (THV) size selection. However, the influence of these incremental data on outcomes has not been evaluated in a randomized study. A single-center prospective, randomized, and open study was performed. Patients referred for transfemoral transcatheter aortic valve implantation with a balloon-expandable endoprothesis were included. THV size selection was performed using either transthoracic and transesophageal echocardiography data (control group) or ultrasound and CT results (CT group). The primary composite end point included the occurrence of stroke, major vascular complications, and moderate or severe paravalvular aortic regurgitation (PAR) at 1 year. Fifty patients (n = 25 in the control and CT groups) were enrolled. The primary composite end point occurred in 40% and 8% of patients from the control and CT groups, respectively (p = 0.008). The Kaplan-Meier analysis revealed a pejorative association with not performing the CT (p = 0.007). A decrease in the occurrence of PAR was observed in the CT group compared with the control group (PAR 28% vs 4%, p = 0.04; major vascular complications 12% vs 4%, p = 0.6; all-cause death 16% vs. 4%, p = 0.34; no stroke). In conclusion, the use of cardiac CT in addition to ultrasound data in THV size selection reduced the long-term occurrence of cardiovascular events.

Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited. OBJECTIVES: The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period. METHODS: TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers. RESULTS: A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased. CONCLUSIONS: The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828).

Respiratory cycle as time basis: an improved method for averaging olfactory neural events.

In the mammalian olfactory system, neural activity appears largely modulated by respiration. Accurate analysis of respiratory synchronized activity is precluded by the variability of the respiratory frequency from trial to trial. Thus, the use of respiratory cycle as the time basis for measuring cell responses was developed about 20 years ago. Nevertheless, averaging oscillatory component of the activity remains a challenge due to their rhythmic features. In this paper, we present a new respiratory monitoring setup based on the measurement of micropressure changes induced by nasal airflow in front of the nostril. Improvements provided by this new monitoring setup allows automatic processing of respiratory signals in order to extract each respiratory period (expiration and inspiration). The time component of these periods, which can differ from trial to trial, is converted into a phase component defined as [-pi, 0] and [0, pi] for inspiration and expiration, respectively. As opposed to time representation, the phase representation is common to all trials. Thus, this phase representation of the respiratory cycle is used as a normalized time basis permitting to collect results in a standardized data format across different animals and providing new tools to average oscillatory components of the activity.

Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss.

OBJECTIVE: The study aimed to investigate whether the degree of postinfectious olfactory loss is reflected in volume of the olfactory bulb (OB). STUDY DESIGN: Retrospective study of 26 patients with postinfectious olfactory loss. MATERIALS AND METHODS: Olfactory function was assessed with the "Sniffin' Sticks" test kit, and the magnetic resonance imaging study focused on OB volume and the olfactory sulcus. RESULTS: The study revealed that 1) OB volume varies with regard to olfactory function, 2) OB volume decreases with duration of olfactory loss, and 3) patients with parosmia had smaller OB volumes than patients who did not report such smell distortions, although their overall olfactory function was not significantly different from each other. CONCLUSION: The study emphasizes that OB volume is a gauge of olfactory function.

Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell.

OBJECTIVE: The aims of this study were to evaluate olfactory function with orthonasal and retronasal testing in patients with posttraumatic olfactory loss and to investigate the relation between residual olfactory function and olfactory bulb (OB) volume. METHOD: A retrospective study of 25 patients with posttraumatic olfactory loss was performed. Orthonasal olfactory function was assessed with the Sniffin' Sticks test kit; retronasal olfactory function was assessed with intraorally applied odors. Magnetic resonance imaging was used to determine OB volume and cortical damage in the frontal and temporal areas. RESULTS: The main outcomes of the present study were the demonstration of a correlation between olfactory function and OB volume, which was more pronounced for retronasal than for orthonasal olfactory function; retronasal olfactory function was most affected in the patients with the most extensive cerebral damage and was least compromised in patients without such damage; OB volumes were smaller in patients with parosmia compared with those without; and the presence of parosmia was clearly associated with the presence of cerebral damage. CONCLUSION: The data confirm that OB volume is an indicator of olfactory function but, interestingly, in this study, it is largely determined by retronasal olfactory sensitivity. In addition, these results emphasize the role of higher cortical centers in olfactory function, and especially in parosmia, which may, at least in some cases, be related to lesions in the fronto-orbital and anterior temporal cortices. It would be of interest to investigate OB volume further in relation to the prognosis of the disorder.

Olfactory function assessed with orthonasal and retronasal testing, olfactory bulb volume, and chemosensory event-related potentials.

OBJECTIVE: To investigate whether differences in olfactory function between healthy individuals and patients with olfactory loss could be detected by various diagnostic tests. DESIGN: Psychophysical testing of orthonasal and retronasal olfactory functions, magnetic resonance imaging of olfactory bulb (OB) volume, and chemosensory event-related potential (ERP) measurement performed between January 1, 2005, and October 31, 2005. SETTING: Academic tertiary referral medical center. PATIENTS: Eleven healthy individuals with normal olfactory function (NL) and 11 patients with nasal polyposis (NP), 11 with posttraumatic olfactory loss (PT), and 11 with postinfectious olfactory loss (PI) were included in this study. MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory test results, magnetic resonance imaging-based OB volume, and ERPs to both olfactory and intranasal trigeminal stimulation. RESULTS: Orthonasal and retronasal testing revealed that NL individuals had higher scores than patients with NP, PT, or PI. Retronasal scores were higher in NP patients compared with PT and PI patients. The OB volumes were higher in NL individuals compared with NP, PT, and PI patients. The OB volumes in PT patients were significantly lower than those from NP and PI patients. Olfactory ERPs were different between NL individuals and NP, PT, and PI patients, and trigeminal ERPs were significantly different when comparing NL individuals with NP patients. For the entire cohort, a significant correlation was found between orthonasal testing and OB volume, between retronasal testing and OB volume, and between both orthonasal and retronasal testing and olfactory ERP amplitudes. Olfactory ERPs were recorded in the 11 NL individuals and in 3 NP, 3 PT, and 4 PI patients, defined as responders. Orthonasal and retronasal test scores, OB volume, and olfactory ERPs were significantly larger in responders compared with nonresponders. CONCLUSIONS: Significant differences in various tests that evaluate olfactory function were detectable in a cohort of NL individuals and NP, PT, and PI patients. This finding suggests that these diagnostic tools provide information in terms of the clinical assessment of olfactory function. Future studies will investigate their combined use in terms of the prognosis of olfactory function in patients with olfactory loss.

close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design.

RATIONALE: Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke AIM: To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. SAMPLE SIZE: Six hundred and sixty-four patients were included in the study. METHODS AND DESIGN: CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years. STUDY OUTCOMES: The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. DISCUSSION: CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke.

Late Outcomes of Transcatheter Aortic Valve Replacement in High-Risk Patients: The FRANCE-2 Registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up. OBJECTIVES: This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry. METHODS: The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used. RESULTS: A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p < 0.001), low body mass index, (p < 0.001), atrial fibrillation (p < 0.001), dialysis (p < 0.001), New York Heart Association functional class III or IV (p < 0.001), higher logistic EuroSCORE (p < 0.001), transapical or subclavian approach (p < 0.001 for both vs. transfemoral approach), need for permanent pacemaker implantation (p = 0.02), and post-implant periprosthetic aortic regurgitation grade ≥2 of 4 (p < 0.001). Severe events according to VARC criteria occurred mainly during the first month and subsequently in <2% of patients/year. Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up. CONCLUSIONS: The FRANCE-2 registry represents the largest database available on late results of TAVR. Late mortality is largely related to noncardiac causes. Incidence rates of severe events are low after the first month. Valve performance remains stable over time.

Quantitative analysis of synchrotron radiation intravenous angiographic images.

A medical research protocol on clinical intravenous coronary angiography has been completed at the European Synchrotron Radiation Facility (ESRF) biomedical beamline. The aim was to investigate the accuracy of intravenous coronary angiography based on the K-edge digital subtraction technique for the detection of in-stent restenosis. For each patient, diagnosis has been performed on the synchrotron radiation images and monitored with the conventional selective coronary angiography method taken as the golden standard. In this paper, the methods of image processing and the results of the quantitative analysis are described. Image processing includes beam harmonic contamination correction, spatial deconvolution and the extraction of a 'contrast' and a 'tissue' image from each couple of radiograms simultaneously acquired at energies bracketing the K-edge of iodine. Quantitative analysis includes the estimation of the vessel diameter, the calculation of the absolute iodine concentration profiles along the coronary arteries and the stenosis degree measurement.

Taste disorders after tonsillectomy: case report and literature review.

The authors describe a case of dysgeusia that occurred during the recovery period after a tonsillectomy. The cause was thought to be a lesion to the lingual branch of the glossopharyngeal nerve because of the location of the symptoms at the posterior region of the buccal cavity and because of the raised electrogustometric thresholds in the posterior region of one half of the tongue. Clarification of this type of case was made by a review of the literature from 1966 to June 2004, carried out with the aid of Medline. From a medicolegal standpoint, it is important to inform the patient of the risk of dysgeusia after tonsillectomy, especially if that patient has a profession in which taste plays an essential role.