Factors associated with patent foramen ovale-related stroke: SAFAS study.

BACKGROUND: Persistent foramen ovale (PFO) contributes to cryptogenic stroke and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke. METHODS: This study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation. PFO was systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression. RESULTS: Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m2 [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke. CONCLUSION: Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes.

[How to manage late periprosthetic fluid collections (seromas) in patients with breast implants?] / Conduite à tenir devant un sérome tardif péri-prothétique.

The widespread use of silicone implants in reconstructive and aesthetic breast surgery led to an increase in the incidence of breast implant associated anaplastic large cell lymphoma, BIA-ALCL, mainly associated with the use of macro-textured breast implants. BIA-ALCL is a serious complication presenting clinically as a late onset periprosthetic seroma. Thus, its occurrence became an alarming sign feared by most plastic surgeons. Therefore, a good knowledge with respect to early diagnosis, subsequent workup, and treatment is crucial in the management of periprosthetic seroma. The diagnosis of late onset seroma is clinically evident. Although idiopathic seroma is the most common cause, BIA-ALCL should be always eliminated. A complete workup is usually necessary. An ultrasound performed by a radiologist specialized in breast imaging followed by an ultrasound guided puncture is imperative. Consequently, the cytological and the bacteriological analysis will orient us toward the etiology (infectious, neoplastic or mechanical). A standardized management of late periprosthetic seroma does not exist, with various factors are to be taken into consideration. These include the surgeon's experience, the diagnosis, and the medical institution facilities. Although idiopathic seroma is managed by a simple puncture and drainage, other causes may require a surgical procedure with implant removal, capsulotomies, and/or total capsulectomies.

Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms.

OBJECTIVES/BACKGROUND: ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus) is a prospective multicentre randomized controlled trial including consecutive patients with ruptured aorto-iliac aneurysms (rAIA) eligible for treatment by either endovascular (EVAR) or open surgical repair (OSR). Inclusion criteria were hemodynamic stability and computed tomography scan demonstrating aorto-iliac rupture. METHODS: Randomization was done by week, synchronously in all centers. The primary end point was 30 day mortality. Secondary end points were post-operative morbidity, length of stay in the intensive care unit (ICU), amount of blood transfused (units) and 6 month mortality. RESULTS: From January 2008 to January 2013, 107 patients (97 men, 10 women; median age 74.4 years) were enrolled in 14 centers: 56 (52.3%) in the EVAR group and 51 (47.7%) in the OSR group. The groups were similar in terms of age, sex, consciousness, systolic blood pressure, Hardman index, IGSII score, type of rupture, use of endoclamping balloon, and levels of troponin, creatinine, and hemoglobin. Delay to treatment was higher in the EVAR group (2.9 vs. 1.3 hours; p < .005). Mortality at 30 days and 1 year were not different between the groups (18% in the EVAR group vs. 24% in the OSR group at 30 days, and 30% vs. 35%, respectively, at 1 year). Total respiratory support time was lower in the EVAR group than in the OSR group (59.3 hours vs. 180.3 hours; p = .007), as were pulmonary complications (15.4% vs. 41.5%, respectively; p = .050), total blood transfusion (6.8 vs. 10.9, respectively; p = .020), and duration of ICU stay (7 days vs. 11.9 days, respectively; p = .010). CONCLUSION: In this study, EVAR was found to be equal to OSR in terms of 30 day and 1 year mortality. However, EVAR was associated with less severe complications and less consumption of hospital resources than OSR.

Molecular allergens in the diagnosis of latex allergy.

BACKGROUND: Molecular allergens enable the definition of sensitization profiles in allergic patients. AIM: To validate the most helpful allergens for the diagnosis of latex allergy in different clinical situations. METHODS: 130 patients suspected to be allergic to latex with positive IgE against natural rubber latex (NRL) have been studied: 97 were confirmed as latex allergic (among which 55 professionally exposed to latex and 35 with a peranaesthetic anaphylactic shock) and 33 were only sensitized to latex without clinical allergy. Each serum was tested for IgE against 9 recombinant latex allergens and bromelain using Phadia ImmunoCAP 250. RESULTS: rHev b 6.01, 6.02, 2 and 5 were the major allergens in the allergic population. An excellent correlation (94%) was observed between IgE against rHev b 6.01 and latex prick test positivities. IgE against rHev b 1, 3 and 5 were more frequent and their levels significantly higher in patients with peranaesthetic anaphylactic shock. Among the asymptomatic patients (29/33 allergic to pollen), NRL IgE positivity is explained by the presence of anti-rHev b 8 and/or anti-carbohydrate IgE. CONCLUSIONS: rHev b 6.01 and rHev b 5 specific IgE are of major interest to confirm latex allergy diagnosis. rHev b 5 is particularly useful in case of monosensitization where clinical symptoms and latex skin prick tests may be discordant, rHev b1 and rHev b 3 are interesting to document multi-operated and peranaesthetic latex allergy. Finally, rHev b 8 is a helpful marker to highlight latex/pollen cross-reactivity which improves the specificity of the serological tests.

[Management of ischemic stroke in the acute phase]. / Prise en charge de l'infarctus cérébral à la phase initiale.

Ischemic stroke accounts for 80% of overall stroke, and is one of the leading causes of death, disability and dementia in worldwide. Management of patients with acute ischemic stroke dramatically improved over time with the implementation of intensive care stroke units, the development of acute recanalization strategies, the optimization of the management of post-stroke complications, and the prevention of early stroke recurrence. The objective of this article is to provide a general overview of the current management of patients with acute ischemic stroke aiming at improving post-stroke outcome.

[Acute management of spontaneous intracerebral hemorrhage]. / Prise en charge aiguë des hémorragies intracérébrales spontanées.

Intracerebral hemorrhage accounts for approximately 15% of the 115,000 strokes occurring each year in France. Although therapeutic strategies are more limited than for ischemic stroke, major points in the management of intracerebral hemorrhage can reduce short term morbidity and mortality by limiting the expansion of the hematoma and the occurrence of early complications, and long term patients' outcome by reducing the risk of recurrence. This article aims to update the key elements that contribute to improve of the prognosis of intracerebral hemorrhage patients.

Oral immunotherapy in food allergies: A practical update for pediatricians.

Food oral immunotherapy (OIT) is a promising treatment for persistent and severe food allergies (FAs) in children, but also for accelerating tolerance to cow's milk and cooked egg in young children. In the near future, pediatricians will increasingly encounter severely allergic children undergoing FA-OIT. FA-OIT consists in daily ingestion of increasing doses of the allergen during the up-dosing phase, and ingestion of a constant dose during the maintenance phase. The global aim is to increase the reactive threshold of allergic patients, and finally enable them to ingest a target quantity of allergen without any reaction throughout the treatment (desensitization). Many studies showed the efficacy of FA-OIT in desensitization, and some of them in sustained unresponsiveness. This corresponds to tolerance after FA-OIT discontinuation, especially for cow's milk and hen's egg allergy. However, there is an ongoing debate about the safety of the treatment. Side effects are frequent, notably aversion to the allergen and oral syndromes as well as systemic allergic symptoms. These reactions occur mainly during the up-dosing phase and become less frequent with time, but they are common causes of FA-OIT discontinuation. Patients and their families must be trained to manage these reactions at home. Long-term side effects can also occur, such as eosinophilic esophagitis. Pediatricians play an important role in maintaining patient motivation; they also provide knowledge on possible allergic reactions and the reactogenic cofactors (mainly fever and viral infection, anti-inflammatory intake, physical activity), and refer the patient to the relevant specialists in the case of long-term care. Other routes of administration for food immunotherapy (epicutaneous and sublingual) and different adjuvant treatments (probiotics, anti-IgE molecule) are currently under study. This will allow us to improve the efficacy of immunotherapy and reduce the risk of any side effects, in order to provide a more favorable risk-benefit ratio.

Vibron-assisted spin excitation in a magnetically anisotropic molecule.

The electrical control and readout of molecular spin states are key for high-density storage. Expectations are that electrically-driven spin and vibrational excitations in a molecule should give rise to new conductance features in the presence of magnetic anisotropy, offering alternative routes to study and, ultimately, manipulate molecular magnetism. Here, we use inelastic electron tunneling spectroscopy to promote and detect the excited spin states of a prototypical molecule with magnetic anisotropy. We demonstrate the existence of a vibron-assisted spin excitation that can exceed in energy and in amplitude a simple excitation among spin states. This excitation, which can be quenched by structural changes in the magnetic molecule, is explained using first-principles calculations that include dynamical electronic correlations.

Atomic-scale spin sensing with a single molecule at the apex of a scanning tunneling microscope.

Recent advances in scanning probe techniques rely on the chemical functionalization of the probe-tip termination by a single molecule. The success of this approach opens the prospect of introducing spin sensitivity through functionalization by a magnetic molecule. We used a nickelocene-terminated tip (Nc-tip), which offered the possibility of producing spin excitations on the tip apex of a scanning tunneling microscope (STM). When the Nc-tip was 100 picometers away from point contact with a surface-supported object, magnetic effects could be probed through changes in the spin excitation spectrum of nickelocene. We used this detection scheme to simultaneously determine the exchange field and the spin polarization of iron atoms and cobalt films on a copper surface with atomic-scale resolution.

Straight motion of half-integer topological defects in thin Fe-N magnetic films with stripe domains.

In thin magnetic films with perpendicular magnetic anisotropy, a periodic "up-down" stripe-domain structure can be originated at remanence, on a mesoscopic scale (~100 nm) comparable with film thickness, by the competition between short-range exchange coupling and long-range dipolar interaction. However, translational order is perturbed because magnetic edge dislocations are spontaneously nucleated. Such topological defects play an important role in magnetic films since they promote the in-plane magnetization reversal of stripes and, in superconductor/ferromagnet hybrids, the creation of superconducting vortex clusters. Combining magnetic force microscopy experiments and micromagnetic simulations, we investigated the motion of two classes of magnetic edge dislocations, randomly distributed in an [Formula: see text]-implanted Fe film. They were found to move in opposite directions along straight trajectories parallel to the stripes axis, when driven by a moderate dc magnetic field. Using the approximate Thiele equation, analytical expressions for the forces acting on such magnetic defects and a microscopic explanation for the direction of their motion could be obtained. Straight trajectories are related to the presence of a periodic stripe domain pattern, which imposes the gyrotropic force to vanish even if a nonzero, half-integer topological charge is carried by the defects in some layers across the film thickness.

Magnetization dynamics of weak stripe domains in Fe-N thin films: a multi-technique complementary approach.

The resonant eigenmodes of an α'-FeN thin film characterized by weak stripe domains are investigated by Brillouin light scattering and broadband ferromagnetic resonance experiments, assisted by micromagnetic simulations. The spectrum of the dynamic eigenmodes in the presence of the weak stripes is very rich and two different families of modes can be selectively detected using different techniques or different experimental configurations. Attention is paid to the evolution of the mode frequencies and spatial profiles under the application of an external magnetic field, of variable intensity, in the direction parallel or transverse to the stripes. The different evolution of the modes with the external magnetic field is accompanied by a distinctive spatial localization in specific regions, such as the closure domains at the surface of the stripes and the bulk domains localized in the inner part of the stripes. The complementarity of BLS and FMR techniques, based on different selection rules, is found to be a fruitful tool for the study of the wealth of localized magnetic excitations generally found in nanostructures.

Chronic low back pain after lumbosacral fracture due to sagittal and frontal vertebral imbalance.

PROBLEM AND HYPOTHESIS: Over time, some patients with unilateral or bilateral lumbosacral injuries experience chronic low back pain. We studied the sagittal and frontal balance in a population with these injuries to determine whether mismatch in the pelvic and lumbar angles are associated with chronic low back pain. PATIENTS AND METHODS: Patients with posterior pelvic ring fractures (Tile C1, C2, C3 and A3.3) that had healed were included. Foreign patients and those with an associated spinal or acetabular fracture or nonunion were excluded. The review consisted of subjective questionnaires, a clinical examination, and standing A/P and lateral stereoradiographic views. The pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), measured lumbar lordosis (LLm), T9 sagittal offset, leg discrepancy (LD) and lateral curvature (LC). The expected lumbar lordosis (LLe) was calculated using the formula LLe=PI+9°. We defined lumbopelvic mismatch (LPM) as the difference between LLm and LLe being equal or greater than 25% of LLe. RESULTS: Fifteen patients were reviewed after an average follow-up of 8.8 years [5.4-15]. There were four Tile C1, five Tile C2, five Tile C3 and one Tile A3.3 fracture. Ten of the 15 patients had low back pain. The mean angles were: LLm 49.6° and LLe 71.9° (P=0.002), PT 21.3°, SS 44.1°, PI 62.9° in patients with low back pain and LLm 57.4° and LLe 63.2° (P=0.55), PT 13°, SS 43.1°, PI 54.2° in those without. LPM was present in 9 patients, 8 of who had low back pain (P=0.02). Six patients, all of whom had low back pain, had a mean LC of 7.5° [4.5-23] (P=0.02). The mean LD was 0.77cm. DISCUSSION: The findings of this small study suggest that patients who experience low back pain after their posterior arch of the pelvic ring fracture has healed, have a lumbopelvic mismatch. Early treatment of these patients should aim to reestablish the anatomy of the pelvic base relative to the frontal and sagittal balance. LEVEL OF EVIDENCE: IV.

[Patients with the highest cardiovascular risk are the least compliant with their antihypertensive therapy (DESIR study)]. / Les hypertendus les plus à risque sont les moins observants (étude DESIR).

AIM OF THE STUDY: To identify the sociodemographic and clinical profile of hypertensive patients who are not compliant with their antihypertensive treatment. METHODS: each cardiologist described his or her next 4 hypertensive patients from a clinical standpoint and gave them a self-administered compliance questionnaire developed by the French Committee to Fight Hypertension, which they returned directly to the analysis center using a postage-paid reply envelope. RESULTS: 1965 patients 63.9 +/- 12.1 years old, 55.3% of whom were male, were included in the study. According to the specific questionnaire, compliance is definitely satisfactory in 35.9% of patients, is probably satisfactory in 28.3%, is probably poor in 19.4% and is definitely poor in 16.4%. Poor compliance is more frequent among men (38.1 vs. 33.4%; p < 0.05), overweight or obese patients (35.8 and 43.0% vs. 30.0%; p < 0.001), diabetics (46.7 vs. 32.3%; p < 0.0001), dyslipidemic patients (39.3 vs. 31.8%; p < 0.001), smokers (50.2 vs. 33.8%; p < 0.0001), those whose father died of cardiovascular causes before 55 years of age (51.6 vs. 34.1%; p < 0.0001) or those with a previous history of CV events (40.6 vs. 32.8%; p < 0.001). The rate of poor compliance increases with the number of risk factors: 27.3% with no risk factor other than high BP, 32.2% with one, 37.2 with 2 and 51.5% with 3 or more (p < 0.0001). Multifactorial analyses confirm the independent effect of obesity, diabetes, smoking, and father's CV death before age 55 on patient compliance. CONCLUSION: patients with the highest CV risk are those who are the least compliant with their antihypertensive treatment. These results raise the question of the appropriateness of the prevention information given to the most at-risk patients.

Gene flow in a facultative apomictic poacea, the savanna grass Hyparrhenia diplandra.

The genetics of the poacea Hyparrhenia diplandra was studied in four natural populations from an ecological station in West Africa, where it makes up 80% of grasses from wet savanna and constitutes a dense continuum of randomly distributed individuals. DNA content and cytogenetical observations suggest it is an allotetraploid. Using two highly variable microsatellites (heterozygosity H = 0.615-0.616), we show that this species is an apomict with rare sexual reproduction events that account for approximately 0.5% of seeds pollinated in the wild. Hexaploid individuals were also produced, corroborating the observation of aberrant genotypes in the wild. The spatial extent of asexual clones in the field was low in comparison with the predominance of apomixis, thus indicating a low dispersal of seeds from their parent. Heterozygosity and departure from Hardy-Weinberg predictions were similar in the four populations, revealing a high apparent selfing rate s = 0.599 among sexually produced seeds. This is an overestimate since we could not distinguish true selfing from reciprocal outcrosses between neighboring individuals from the same apomictic clone. Gene flow by pollen could be substantial, possibly explaining the absence of isolation by distance in the studied area.

Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?

AIM: This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS: A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated. RESULTS: Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) µg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. CONCLUSION: Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).

Evidence for N-glycosylation and ubiquitination of the prolactin receptor expressed in a baculovirus-insect cell system.

The molecular mass of the rabbit prolactin receptor (rbPRLR) deduced from cDNA cloning is 66 kDa. However, the molecular mass of the full-length receptor expressed in the insect Sf9 cells was found to be 94 kDa. In order to explain this discrepancy, we analyzed the possible post-translational modifications of the PRLR. Sf9 cells were infected with recombinant baculoviruses in the presence of tunicamycin, an inhibitor of N-glycosylation. Results showed that an additional approximately 9 kDa of the extracellular domain could be attributed to the N-glycosylation and another additional approximately 20 kDa covalent modification occurred in the cytoplasmic part of the receptor. Western blot analysis, using anti-ubiquitin antibodies, revealed that the rbPRLR was ubiquitinated in its cytoplasmic domain.

[Medical treatment of cardiac insufficiency. Advances and controversies]. / Le traitement médical de l'insuffisance cardiaque. Acquisitions et controverses.

In the treatment of chronic congestive heart failure (CHF), digitalis has empirically proved to be effective in reducing functional signs and symptoms. However, it is among patients treated with digitalis, diuretics and salt-free diet that mortality is still high. Moreover, the use of digitalis derivatives in CHF with sinus rhythm is controverted due to the frequent toxicity of these drugs and to their allegedly weak positive inotropic activity. Current research in this field therefore is oriented towards non-digitalis cardiotonic drugs capable of increasing intracellular calcium concentrations. In actual fact, a better understanding of physiopathological mechanisms has led to the use of vasodilators, and these in turn have shed additional light on regional blood flows and on the role of the renin-angiotensin-aldosterone system. Added to the digitalis-diuretics therapy, vasodilators not only have beneficial effects on haemodynamic parameters and functional symptoms, but they reduce mortality in patients with CHF: recent studies have demonstrated an increase in survival as compared to conventional treatment. This has revived the problem of whether vasodilators should be prescribed in the early stages of CHF, either alone or combined with the usual drugs.

Atrial fibrillation and anticoagulation.

Atrial fibrillation (AF) increases the risk of ischemic stroke due to the formation of a thrombus within left atrium. Thus, adjusted-dose (optimal INR: 2-3) anticoagulant therapy such as warfarin dramaticaly decreases this risk of embolic events both in primary and secondary prevention but slightly increases the risk of bleeding, particularly in the elderly. This explains that, although the benefit has been clearly demonstrated, the anticoagulant therapy remains underused. The efficacy of low doses of aspirin is less clear but it may be appropriate in younger patients with lone AF because of a low risk of embolic events. The combination of low doses of warfarin and aspirin should not be given. In case of contraindication to warfarin and aspirin, some others drugs such as indobufen or dipyridamole may be given but the most promising drug is ximelagatran, a direct thrombin inhibitor, which appears to be as effective than warfarin with a lower incidence of bleedings. For patients in AF who require urgent cardioversion, intravenous unfractionated heparin remains the anticoagulant of choice but an approach combining low-molecular-weight heparin and transesophageal echocardiography has been proposed. For each patient the decision of treatment must be tightly correlated to the benefit-risk ratio.