Gamma-Linolenic Acid Levels Correlate with Clinical Efficacy of Evening Primrose Oil in Patients with Atopic Dermatitis

Introduction: Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. Methods: The open study included 21 patients with AD. EPO (4-6g) was administered daily for 12weeks. Before treatment, and 4 and 12weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. Results: A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12weeks after initiation of EPO treatment. In the per-protocol population (n=14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P=0.008). Conclusion: The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53

Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis.

INTRODUCTION Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. METHODS The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. RESULTS A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008). CONCLUSION The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

OBJECTIVE The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2020

Das Klima ändert - auch in der Schweiz. Die wichtigsten Ergebnisse des dritten Wissenstandsberichts des IPCC aus der Sicht der Schweiz

Der dritte Wissensstandsbericht (TAR) des IPCC liegt vor. Eine Arbeitsgruppe des OcCC hat die wichtigsten Ergebnisse des TAR aus der Sicht der Schweiz zusammengefasst: Beobachtungen zeigen insgesamt eine Erwärmung der Erde und weitere Veränderungen des Klimasystems: Die 1990er Jahre waren wahrscheinlich das wärmste Jahrzehnt und 1998 war das wärmste Jahr der letzten 1000 Jahre. Im 20. Jahrhundert nahmen Niederschläge über den Kontinenten in mittleren bis hohen Breiten der Nordhemisphäre zu. Schnee- und Eisbedeckung nahmen ab und der Meeresspiegel ist angestiegen. Der grösste Teil des Temperaturanstiegs der letzten 50 Jahre ist wahrscheinlich den Aktivitäten des Menschen zuzuschreiben. Die Konzentrationen der Treibhausgase Kohlendioxid, Methan und Lachgas haben seit Beginn der Industrialisierung stark zugenommen. Klimamodelle können die beobachtete Erwärmung der letzten 50 Jahre nur simulieren, wenn sie den Anstieg der Treibhausgase berücksichtigen. Menschliche Einflüsse werden die Zusammensetzung der Atmosphäre weiter verändern. Bis Ende des 21. Jahrhunderts wird die globale mittlere Temperatur um 1.4 bis 5.8°C steigen. Die Temperatur wird über Land und im Alpenraum sehr wahrscheinlich stärker ansteigen als im globalen Mittel. Schnee- und Eisbedeckung werden weiter abnehmen und der Meeresspiegel wird weiter ansteigen. Die durch den Menschen verursachte Klimaänderung wird mehrere Jahrhunderte andauern. Eine Stabilisierung des atmosphärischen CO2-Gehaltes verlangt, dass die globalen Emissionen unter die heutigen Werte gesenkt werden. Langfristig müssten die Emissionen auf einen Bruchteil der heutigen Werte abfallen. Die Klimaänderung hat Auswirkungen auf Natur und Gesellschaft: Als Folge der Klimaänderung wird der Rückgang der Gletscher und des Permafrosts in den Bergen anhalten. In den Alpen werden die Niederschläge in Form von Schnee abnehmen und in einzelnen Regionen sogar ganz ausbleiben. In vielen Regionen dürften insbesondere im Winter Häufigkeit und Stärke der Hochwasser zunehmen. Die Wirkung der Klimaänderung auf Ökosysteme ist regional unterschiedlich und erfolgt im Zusammenspiel mit anderen Umwelteinflüssen. Die Artenzusammensetzung der natürlichen Ökosysteme wird sich verändern. In der Landwirtschaft wird die ertragssteigernde Wirkung erhöhter CO2-Konzentrationen und wärmerer Temperaturen durch andere Faktoren begrenzt. Durch die Klimaänderung ist anfänglich mit einer Zunahme der Senkenwirkung von Landökosystemen zu rechnen. Bei einer sich weiter fortsetzenden Klimaänderung können sich die Ökosysteme aber auch wieder in Kohlenstoff-Quellen verwandeln. In gemässigten Klimazonen werden wärmere Sommer und häufigere Hitzewellen zu mehr Todesfällen führen. Gesundheitliche Auswirkungen der Luftverschmutzung werden durch die Klimaänderung wahrscheinlich noch verstärkt. Die Verbreitung und Häufigkeit von Infektionskrankheiten wird sich verändern. Volkswirtschaftliche und versicherte Schäden durch wetterbedingte Naturkatastrophen haben global stark zugenommen. Im Finanzsektor sind vor allem die Versicherungen direkt betroffen.Ein klarer Zusammenhang zwischen wachsenden Schäden und Klimaänderung lässt sich noch nicht herstellen. Es gibt Möglichkeiten, die Emissionen von Treibhausgasen durch technische Massnahmen zu senken und den Anstieg der Treibhausgaskonzentrationen durch biologische Massnahmen abzuschwächen: Fehlende ökonomische und ausbleibende politische Massnahmen erschweren oft die technisch mögliche Reduktion der Treibhausgasemissionen. Hemmnisse und Marktunvollkommenheit behindern die Verbreitung von Technologien und Verfahrensweisen. Zur Reduktion der Treibhausgase stehen zahlreiche Politikoptionen zur Verfügung. Dabei ermöglicht eine Kombination von Massnahmen eine erfolgreiche Klimapolitik. International sollten die Massnahmen und politischen Strategien koordiniert und harmonisiert werden. Eine zentrale Rolle spielen die Kosten der Massnahmen zur Abschwächung der Klimaänderung. Durch die flexiblen Mechanismen des Kyoto-Protokolls können sie entscheidend gesenkt werden. Es besteht kein Zusammenhang zwischen der Höhe einer CO2-Steuer und der Entwicklung des BIP

Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke)

International audienceAbstract Background Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV− group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4–7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke. Discussion The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. Trial registration ClinicalTrials.gov NCT02554487 , retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521)

Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper. Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery. Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential. Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland

Direct crosstalk between mast cell–TNF and TNFR1-expressing endothelia mediates local tissue inflammation

Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell–mediated autoimmune diseases. By dissecting Th1 cell–mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (ECs). Adoptive transfer and mast cell knockin experiments into KitW/KitW-v, TNF−/−, and TNFR1−/− mice showed that the signaling defect exclusively affects mast cell–EC interactions but not T cells or antigen-presenting cells. As a consequence, TNFR1−/− mice had strongly reduced mRNA and protein expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 during DTHR elicitation. In consequence, intravital fluorescence microscopy revealed up to 80% reduction of leukocyte rolling and firm adhesion in TNFR1−/− mice. As substitution of TNF−/− mice with TNF-producing mast cells fully restored DTHR in these mice, signaling of mast cell-derived TNF through TNFR1-expressing ECs is essential for the recruitment of leukocytes into sites of inflammation