Aortenisthmusstenosen bei Kindern.Untersuchung des mittelfristigen postoperativen Verlaufs in Abhängigkeit von morphologischer Ausgangslage, Operationsalter und Operationstechnik.

1 Background There is a controverse discussion in literature about the influence of surgical tech¬niques and the age at operation on the later outcome in patients after surgical repair of aortic coarctation. Especially the occurence of a recoarctation or the persistence re¬spectively the development of arterial hypertension is important for the postoperative mortality and morbidity. In this context the aim of this study is to figure out how the surgical techniques and the age at operation determine the postoperative development of the aortic arch and how many patients need long-term medical treatment because of arterial hypertension. There is a special interest for the aortic diameter in the area of coarctation and for patients with hypoplastic aortic arch. 2 Methods The retrospective study includes 181 patients with isolated or complex aortic coarc¬tation. All of them were operated between 1st of January 1990 and 31st December 2000, mostly by resection and end-to-end anastomosis or by patch aortoplasty. The patients are between 3 days and 16 years old at time of the primary surgery. The median age was 73 days. The follow-up time was determined on 31st December 2001. Following facts were among other things taken from the patients documents: surgical techniques, systolic blood pressure of arms and legs pre- and postoperative, post¬operative echocardiogram or aortography, 24-hour ambulatory blood pressure and anti¬hypertensive treatment. The aortic diameter is measured endsystolic at defined mea¬sure¬¬points in coronar-aortography (aorta ascendens, truncus brachiocephalicus, arteria subclavia sinister, at the point of maximal coarctation and aorta descendens). 3 Results During the follow-up time occure 32,6% recoarctations and 7,8% of all patients are re¬operated. The overall mortality is 3,3%. In total 24% of the patients have to be treated because of persistent hypertension. The postoperative growth of the aortic arch is signi¬¬ficantly in the area of maximal coarctation and at the truncus brachiocephalicus. The diameter of the aorta is at these points even growing when the aortic arch was hypoplastic preoperative. In these cases there is no significant difference between the surgical techniques and the age at operation. The systolic blood pressure on the arm is postoperative significantly lower when the coarctation is repaired after the first four weeks of life. The best persistent reduction of systolic blood pressure is seen in pa¬tients operated between the 3th and 12th months of life. If surgical repair is done during the first four weeks of life the postoperative blood pressure is significantly higher whereas it is highest after patch aortoplasty. Patients with the diagnose hypolpastic aortic arch or those which have a maximal aortic diameter of 70% of the aorta descen¬dens measured nearby the arteria subclavia sinister have a significant higher post¬operative blood pressure. Patients who have a diastolic gradient in postopertive echocardiogram show more often recoarctations. If upper/lower limb pressure gradi¬ent is more than 20 mmHg postoperative the risk for development of a recoarcta¬tion is higher. 4 Conclusions The best result regarding postoperative arterial hypertension is expected when surgical repair of an aortic coarctation is done after the first month of life and during the first year. The patch aortoplasty should especially be avoided when operation must be done in neonates. During the postoperative follow-up blood pressure should be controlled regularly at rest and if possible over 24-hours or as exercise testing. In addition the study recommends transthoracic echocardiogram. If the pressure gradient upper/lower limb is increased (more than 20 mmHg blood pressure or more than 36 mmHg echocardio¬gram) further diagostics should be done because of the risk of recoarctation.1 Hintergrund und Ziele In der Literatur wird kontrovers diskutiert, wie ein bestimmtes Operationsverfahren oder -alter den postoperativen Verlauf nach Korrektur einer Aortenisthmusstenose beein¬flussen kann. Besonders wichtig ist das Auftreten einer Recoarctation oder einer arte¬riellen Hypertonie, da diese beiden Faktoren eine entscheidende Auswirkung auf die postoperative Mortalität und Morbidität haben. Hauptanliegen dieser Arbeit ist heraus¬zufinden, welchen Einfluss die Operationstechnik und das Operationsalter auf die wei¬tere Entwicklung der Aortenbogenmorphologie haben und wie viele Patienten im mit¬telfristigen postoperativen Verlauf hyperton sind. Von besonderem Interesse sind dabei das Aorten¬bogenlumen im Bereich der Stenose und ein hypoplas¬tischer Aortenbogen. 2 Methoden In die retrospektive Studie werden insgesamt 181 Patienten mit einfacher oder kompli¬zierter Aortenisthmusstenose eingeschlossen, die im Zeitraum von 01.01.1990 bis 31.12.2000 überwiegend mit der Resektion und Anastomose oder der Patch-Technik operiert werden. Die Patienten sind zum Zeitpunkt der Operation 3 Tage bis 16 Jahre alt, im Median 73 Tage. Der Nachbeobachtungszeitraum ist bis 31.12.2001 festgelegt. Aus den Akten werden u.a. folgende Daten entnommen: Opera¬tionstechnik bei primä¬rer Operation und Reoperation, arterielle systolische Blutdruckwerte präoperativ und im post¬operativen Verlauf an oberer und unterer Extremität, postoperative Ergebnisse aus Echokardiographie oder Angiographie, Langzeit¬blut¬druck¬messung und antihyper¬ten¬sive Therapie. Das Aortenbogenlumen wird in der Herzkatheteruntersuchung mit Angi¬ographie an den definierten Gefäßabschnitten (Aorta ascendens, Truncus brachio¬cephalicus, Arteria subclavia sinistra, maximale Stenosierung und Aorta descendens) endsystolisch gemessen. 3 Ergebnisse Im Beobachtungszeitraum treten 32,6% Restenosierungen auf und bei 7,8% der Pati¬enten werden Reoperationen durchgeführt. Die Gesamtmortalität liegt bei 3,3%. Insge¬samt werden 24% der Patienten postoperativ weiterhin antihypertensiv behandelt. Durch die Operation kommt es zu einer signifikanten Zunahme des Aorten¬bogen¬lu¬mens im Bereich der Stenose und des Truncus, auch wenn das Lumen in diesem Be¬reich präoperativ im Sinne einer Aortenbogenhypoplasie vermindert war. Weder ein bestimmtes Operationsalter noch ein spezielles Operationsverfahren haben dabei sig¬ni¬fikanten Einfluss. Der arterielle systolische Blutdruck am Arm nimmt bei allen Pati¬enten, die nach den ersten 4 Lebenswochen operiert werden, postoperativ signifikant ab. Eine dauerhafte Abnahme zeigt sich am deutlichsten bei den ab dem dritten Lebens¬monat innerhalb des ersten Lebensjahres operierten Patienten. Bei Neuge¬borenen ist der postoperative Blutdruck signifikant höher, wobei nach der Operation mit der Patch-Technik anhaltend die höchsten Werte gemessen werden. Im gesamten Patientengut bedingt die Zusatzdiagnose Aortenbogenhypoplasie oder ein maximales präoperatives Aortenbogenlumen von 70% am Abgang der Arteria subclavia sinistra einen signifikant höheren postoperativen Blutdruck. Bei einer post¬operativen Blut¬druckdifferenz von mind. 20 mmHg zwischen Arm und Bein oder einem diastolischen Gradienten in der postoperativen Echokardiographie treten häufiger Restenosierungen auf. 4 Praktische Schlussfolgerungen Bei der Operation nach dem ersten Lebensmonat und innerhalb des ersten Lebens¬jahres ist bzgl. einer postoperativen arteriellen Hypertonie der günstigste Verlauf zu erwarten. Bei Neugeborenen sollte der Einsatz der Patch-Technik bei der primären Operation vermieden werden. Zur postoperativen Verlaufskontrolle sind die Blutdruck¬messung in Ruhe, die 24h-Messung und die Echokardiographie zu empfehlen. Bei erhöhten Blutdruckgradienten (> 20 mmHg in der Blutdruckmessung oder > 36 mmHg in der Echokardiographie) sollte weitere Diagnostik durchgeführt werden, da eine relevante Restenosierung vorliegen kann. Falls möglich, sollte eine Ergometrie erfolgen, um eine belastungs¬induzierte Hypertonie frühzeitig zu erkennen

Eine Aufgabe mit Schlüsselfunktion

Erfahrungsbericht: Im Rahmen ihres Studiums Master of Science in Nursing an der Zürcher Hochschule für Angewandte Wissenschaften in Winterthur absolvierte Cornelia Stricker ein Workshadowing im Pflegedienst des Universitätskinderspitals Zürich. Innerhalb von zwei Wochen erhielt sie einen direkten Einblick in die Pflegepraxis der Pflegeexpertinnen APN Kardiologie, APN Onkologie und APN Kontinenz und über ihre Verankerung in der klinischen Praxis. Hier beschreibt sie die vielfältigen Aufgaben pädiatrischer Pflegeexperten APN in der klinischen Praxis und zeigt Möglichkeiten des Umgangs auf

Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy

The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High‐serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin‐1β, and urokinase‐type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy.publishedVersio

The Anabolic Androgenic Steroid Fluoxymesterone Inhibits 11β-Hydroxysteroid Dehydrogenase 2-Dependent Glucocorticoid Inactivation

Anabolic androgenic steroids (AAS) are testosterone derivatives used either clinically, in elite sports, or for body shaping with the goal to increase muscle size and strength. Clinically developed compounds and nonclinically tested designer steroids often marketed as food supplements are widely used. Despite the considerable evidence for various adverse effects of AAS use, the underlying molecular mechanisms are insufficiently understood. Here, we investigated whether some AAS, as a result of a lack of target selectivity, might inhibit 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2)-dependent inactivation of glucocorticoids. Using recombinant human 11β-HSD2, we observed inhibitory effects for several AAS. Whereas oxymetholone, oxymesterone, danazol, and testosterone showed medium inhibitory potential, fluoxymesterone was a potent inhibitor of human 11β-HSD2 (half-maximal inhibitory concentration [IC50] of 60-100nM in cell lysates; IC50 of 160nM in intact SW-620, and 530nM in MCF-7 cells). Measurements with rat kidney microsomes and lysates of cells expressing recombinant mouse 11β-HSD2 revealed much weaker inhibition by the AAS tested, indicating that the adverse effects of AAS-dependent 11β-HSD2 inhibition cannot be investigated in rats and mice. Furthermore, we provide evidence that fluoxymesterone is metabolized to 11-oxofluoxymesterone by human 11β-HSD2. Structural modeling revealed similar binding modes for fluoxymesterone and cortisol, supporting a competitive mode of inhibition of 11β-HSD2-dependent cortisol oxidation by this AAS. No direct modulation of mineralocorticoid receptor (MR) function was observed. Thus, 11β-HSD2 inhibition by fluoxymesterone may cause cortisol-induced MR activation, thereby leading to electrolyte disturbances and contributing to the development of hypertension and cardiovascular diseas

Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase of the renin-angiotensin-system (RAS) which is known to cleave several substrates among vasoactive peptides. Its preferred substrate is Angiotensin II, which is tightly involved in the regulation of important physiological functions including fluid homeostasis and blood pressure. Ang 1–7, the main enzymatic product of ACE2, became increasingly important in the literature in recent years, as it was reported to counteract hypertensive and fibrotic actions of Angiotensin II via the MAS receptor. The functional connection of ACE2, Ang 1–7, and the MAS receptor is also referred to as the alternative axis of the RAS. In the present paper, we describe the recombinant expression and purification of human and murine ACE2 (rhACE2 and rmACE2). Furthermore, we determined the conversion rates of rhACE2 and rmACE2 for different natural peptide substrates in plasma samples and discovered species-specific differences in substrate specificities, probably leading to functional differences in the alternative axis of the RAS. In particular, conversion rates of Ang 1–10 to Ang 1–9 were found to be substantially different when applying rhACE2 or rmACE2 in vitro. In contrast to rhACE2, rm ACE2 is substantially less potent in transformation of Ang 1–10 to Ang 1–9

Hsa-miR-375 is a predictor of local control in early stage breast cancer

Background: A long-term analysis by the Early Breast Cancer Trialist Group (EBCTG) revealed a strong correlation between local control and cancer-specific mortality. MicroRNAs (miRs), short (20-25 nucleotides) non-coding RNAs, have been described as prognosticators and predictors for breast cancer in recent years. The aim of the current study was to identify miRs that can predict local control after breast conserving therapy (BCT) in early stage breast cancer. Results: Clinical data of 46 early stage breast cancer patients with local relapse after BCT were selected from the institutional database. These patients were matched to 101 control patients showing identical clinical features but without local relapse. The study was conducted in two steps. (1) In the pilot study, 32 patients (16 relapses versus 16 controls) were screened for the most de-regulated microRNAs (= candidate microRNAs) in a panel of 1250 miRs by microarray technology. Eight miRs were found to be significantly de-regulated. (2) In the validation study, the candidate microRNAs were analyzed in an independent cohort of 115 patients (30 relapses versus 85 controls) with reverse transcription quantitative polymerase chain reaction (RT-qPCR). From these eight candidates, hsa-miR-375 could be validated. Its median fold change was 2.28 (Mann-Whitney U test, corrected p value = 0.008). In the log-rank analysis, high expression levels of hsa-miR-375 correlated with a significantly higher risk of local relapse (p = 0.003). In a multivariate analysis (forward stepwise regression) including established predictors and prognosticators, hsa-miR-375 was the only variable that was able to distinguish the statistical significance between relapse and control groups (raw p value = 0.000195 HR = 0.76, 95 % CI 0.66-0.88;corrected p value = 0.005). Conclusions: Hsa-miR-375 predicts local control in patient with early stage breast cancer, especially in estrogen receptor alpha (ER-alpha)-positive patients. It can therefore serve as an additional molecular marker for treatment choice independently from known predictors and prognosticators. Validation in larger prospective studies is warranted

Zürich Image Monitoring: Studie über das Image der Region Zürich

"Das Zürich Image Monitoring (ZIM) dient zur Messung des Images der Region Zürich bei der Bevölkerung im Kanton, in der Schweiz und im Ausland. Gemessen wurde das Image in den Aufgabenfeldern des Kantons und in weiteren standortrelevanten Themenfeldern. Das ZIM bietet ein wirklichkeitsgetreues Abbild der Meinungen und Einstellungen, welche die verschiedenen Zielgruppen haben. Es bietet eine Datenbasis für die Ableitung von Massnahmen durch die politischen Entscheidungsträgerinnen und Entscheidungsträger. Anlass für das Zürich Image Monitoring ist, dass das Image von grosser Bedeutung für die Region Zürich und für ihre Zielgruppen ist. Dies haben weltweit Standorte erkannt, die in direkter Konkurrenz zum Standort Zürich stehen. Sie schenken ihrem Image vermehrte Aufmerksamkeit. Um im internationalen Wettbewerb zu bestehen, ist daher die Kenntnis des eigenen Images von grosser Bedeutung. Kenntnis des eigenen Images ist für die Region Zürich als Standort wichtig. Hintergrund Zahlreiche Untersuchungen belegen die Bedeutung von Images für menschliche Entscheidungen. Ein Grund dafür ist die grosse Menge an Informationen, welche in der Wissens- und Informationsgesellschaft täglich anfällt. Images erfüllen hier die Funktion von mentalen Faustregeln, welche die Entscheidungsfindung erleichtern. Dies gilt auch für Entscheidungen, die eine Region betreffen, etwa die Standortwahl bei der Firmengründung oder bei der Entscheidung einer Familie zur Wohnsitznahme. Das Image beeinflusst die Entscheidung für oder wider einen Standort und die Zufriedenheit mit einem gewählten Standort. Der Erfolg eines Standorts hängt auch davon ab, welches Image er bei seinen Zielgruppen hat. Dabei spielen subjektive Einflussgrössen eine bedeutende Rolle. Es ist oft sogar weniger wichtig, welche Eigenschaften eine Region tatsächlich hat, sondern wie die Wahrnehmung dieser Eigenschaften ist. Der Auftrag dieser Studie bestand daher aus der Messung der imagerelevanten Wahrnehmungen bei den Zielgruppen des Kantons. Gemessen wurde die Wahrnehmung der Region Zürich aus allen relevanten Blickwinkeln." (Autorenreferat

Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. Methods: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. Results: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p < 0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p < 0.001] were significantly associated with in-hospital mortality. Conclusions: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. Clinical trial registration: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016

LSE’s experts explain what awaits Britain and Europe ahead of Brexit

On Thursday 8 December, LSE hosted a day of EU- and UK-focused expert panel events and networking activities about Brexit. Below is the full programme, along with audio recordings of each session

Ipilimumab in a real-world population: A prospective Phase IV trial with long-term follow-up

Ipilimumab was the first treatment that improved survival in advanced melanoma. Efficacy and toxicity in a real-world setting may differ from clinical trials, due to more liberal eligibility criteria and less intensive monitoring. Moreover, high costs and lack of biomarkers have raised cost-benefit concerns about ipilimumab in national healthcare systems and limited its use. Here, we report the prospective, interventional study, Ipi4 (NCT02068196), which aimed to investigate the toxicity and efficacy of ipilimumab in a real-world population with advanced melanoma. This national, multicentre, phase IV trial included 151 patients. Patients received ipilimumab 3 mg/kg intravenously and were followed for at least 5 years or until death. Treatment interruption or cessation occurred in 38%, most frequently due to disease progression (19%). Treatment-associated grade 3 to 4 toxicity was observed in 28% of patients, and immune-related toxicity in 56%. The overall response rate was 9%. Median overall survival was 12.1 months (95% CI: 8.3-15.9); and progression-free survival 2.7 months (95% CI: 2.6-2.8). After 5 years, 20% of patients were alive. In a landmark analysis from 6 months, improved survival was associated with objective response (HR 0.16, P = .001) and stable disease (HR 0.49, P = .005) compared to progressive disease. Poor performance status, elevated lactate dehydrogenase and C-reactive protein were identified as biomarkers. This prospective trial represents the longest reported follow-up of a real-world melanoma population treated with ipilimumab. Results indicate safety and efficacy comparable to phase III trials and suggest that the use of ipilimumab can be based on current cost-benefit estimates.publishedVersio