Pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation

Viele Studien zeigen, dass die zirkumferente Pulmonalvenenisolation(CPVI) bei Patienten mit paroxysmalem Vorhofflimmern der CPVI bei Patienten persistierendem VHF überlegen ist. Dies konnte in der aktuellen Untersuchung bestätigt werden. Obwohl sich die Untersuchungsmodalitäten und die CPVI bei Patienten mit persistierendem VHF aufwendiger darstellen, sind weder die Komplikationsrate noch die Inzidenz von atypischem Vorhofflattern nach der RFA bei diesen Patienten erhöht. Somit ist weder die Komplikationsrate noch das Auftreten von atypischem Vorhofflattern an die Form des Vorhofflimmerns gebunden. Die Reevaluation der Pulmonalvenenisolation bei Patienten mit Rezidiven zeigt, dass die erholte Leitungsfähigkeit der Pulmonalvenen bei insgesamt 92% der Patienten den Grund für den Rückfall darstellte. Dies hebt die Rolle einer anhaltenden CPVI nochmals in den Vordergrund. Das Bestehen von Klappenvitien und das Auftreten eines Frührezidivs waren in der aktuellen Untersuchung signifikante Prädiktoren für das Auftreten eines Rezidivs nach der Erstablation. Das Bestehen einer arteriellen Hypertonie war ein signifikanter Prädiktor bei Patienten mit paroxysmalem VHF und die COPD wies einen Trend für einen Misserfolg bei Patienten mit persistierendem VHF auf. Diese Ergebnisse stellen einen Ansatz für eine individuellere Behandlung der Patienten mit Vorhofflimmern dar. Zudem zeigte die aktuelle Untersuchung, dass auch Patienten, welche nach der Ablation ein Jahr und mehr im Sinusrhythmus verblieben sind, weiterhin Rückfälle erleiden. Die Gefahr eines Rezidivs, wie auch das erhöhte Schlaganfallrisiko, besteht somit auch bei langjährig erhaltenem Sinusrhythmus weiter. Folglich sollte auch bei bisher rezidivfreien Patienten die Antikoagulation fortgeführt werden, wenn der Patient (nach CHADS2) ein erhöhtes thromboembolisches Risiko aufweist.Several studies have shown pulmonary vein isolation to be less promising in patients with persistent atrial fibrillation than in patients with paroxysmal atrial fibrillation (AF). This finding is reproduced in the current study. While the procedure in itself proves to be more complex in patients with persistent atrial fibrillation, the incidence of complications and proarythmias after the interventions are similar in both groups. A reevaluation of the electric isolation of the pulmonary veins at redo interventions following relapses of atrial fibrillation shows the recovery of electric conduction from at least one pulmonary vein to be the origin of the relapse in 92% of patients. This underlines the importance of the pulmonary veins in the genesis as well as perpetuation of atrial fibrillation Further, the current study shows that the risk for recurrence remains even in patients with a long term success. Thus, an anticoagulation therapy should not be discontinued in such patients, as the increased thromboembolic risk persists. The existence of valve dysfunction and the occurrence of an early recurrence are significant predictors for an unsuccessful primary intervention. In patients with paroxzsmal AF the existence of arterial hypertension is a predictor for relapse and in patients with persistent AF the existence of a COPD shows a trend for a recurrence of AF. Further studies are needed to make a clear statement on behalf of valid predictors for a recurrence of AF

Which treatment strategies for polyrefractory Neuro-Behçet disease?

Neurological involvement is one of the most disabling complications of Behçet disease. Most patients with Neuro-Behçet disease (NBD) adequately respond to corticosteroids and usual immunosuppressive therapies such as azathioprine, cyclophosphamide or methotrexate. Those remaining refractory require an alternative treatment approach. The use of monoclonal antibodies against tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) receptor has increased over time since promising results have been shown in several case reports or small case series. [...

Syndrome of the trephined revealed by vertical diplopia.

A 29 year-old man underwent a bi-frontal decompressive craniectomy to drain a life-threatening post-traumatic intraparenchymal hematoma. The bone flap became infected and had to be removed 13 months after the initial surgery. Seven months later, the patient complained of vertical diplopia which was more prominent in the evening and disappeared upon awakening, suggesting posture-related occurrence of symptoms. Ophthalmologic examination revealed a limitation of the upward gaze of the left eye with upbeat nystagmus, and a bilateral horizontal gaze evoked nystagmus associated with irregular dysmetric saccades. Ophthalmological examination suggested a midbrain dysfunction. MRI revealed an impingement of the mesencephalon by brain shift after craniectomy suggesting syndrome of the trephined (ST)/sinking skin flap syndrome. Cranioplasty was performed, and symptoms disappeared shortly after. A follow-up MRI 2 months later showed a normalized shape of the previously impinged mesencephalon. [...

Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear

Association Between Use of a Flying Intervention Team vs Patient Interhospital Transfer and Time to Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke in Nonurban Germany

Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. Exposures: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. Main Outcomes and Measures: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). Results: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P?<?.001). There was no significant difference in modified Rankin Scale score after 3 months between patients in the flying team (n?=?59) and transfer (n?=?57) groups who received EVT (median [IQR] score, 3 [2-6] vs 3 [2-5]; adjusted common odds ratio for less disability, 1.91 [95% CI, 0.96-3.88]; P?=?.07). Conclusions and Relevance: In a nonurban stroke network in Germany, deployment of a flying intervention team to local stroke centers, compared with patient interhospital transfer to referral centers, was significantly associated with shorter time to EVT for patients with acute ischemic stroke. The findings may support consideration of a flying intervention team for some stroke systems of care, although further research is needed to confirm long-term clinical outcomes and to understand applicability to other geographic settings

Bioavailability, metabolism, and excretion of a complex Alternaria culture extract versus altertoxin II: a comparative study in rats

Despite the frequent infection of agricultural crops by Alternaria spp., their toxic secondary metabolites and potential food contaminants lack comprehensive metabolic characterization. In this study, we investigated their bioavailability, metabolism, and excretion in vivo. A complex Alternaria culture extract (50 mg/kg body weight) containing 11 known toxins and the isolated lead toxin altertoxin II (0.7 mg/kg body weight) were administered per gavage to groups of 14 Sprague Dawley rats each. After 3 h and 24 h, plasma, urine and feces were collected to determine toxin recoveries. For reliable quantitation, an LC–MS/MS method for the simultaneous detection of 20 Alternaria toxins and metabolites was developed and optimized for either biological matrix. The obtained results demonstrated efficient excretion of alternariol (AOH) and its monomethyl ether (AME) via feces (> 89%) and urine (> 2.6%) after 24 h, while the majority of tenuazonic acid was recovered in urine (20 and 87% after 3 and 24 h, respectively). Moreover, modified forms of AOH and AME were identified in urine and fecal samples confirming both, mammalian phase-I (4-hydroxy-AOH) and phase-II (sulfates) biotransformation in vivo. Despite the comparably high doses, perylene quinones were recovered only at very low levels (altertoxin I, alterperylenol, < 0.06% in urine and plasma, < 5% in feces) or not at all (highly genotoxic, epoxide-holding altertoxin II, stemphyltoxin III). Interestingly, altertoxin I was detected in all matrices of rats receiving altertoxin II and suggests enzymatic de-epoxidation in vivo. In conclusion, the present study contributes valuable information to advance our understanding of the emerging Alternaria mycotoxins and their relevance on food safety.© The Author(s) 201

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

International audienceBackground and Purpose— Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset

Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.status: publishe

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None