Entwicklung des circadianen und ultradianen Biorhythmus bei Frühgeborenen

Entwicklung des circadianen und ultradianen Biorhythmus bei Frühgeborenen Zusammenfassung Hintergrund: Viele physiologische Funktionen des Menschen wie Hormonsekretion, Schlaf-Wach-Rhythmus oder Körpertemperatur unterliegen einem sich regelmäßig wiederholenden Muster, dem biologischen Rhythmus. Externe Umwelteinflüsse wie Licht, Temperatur, Nahrungsaufnahme und soziale Kontakte stellen entscheidende externe Zeitgeber dar, die zur Ausbildung biologischer Rhythmen beitragen und endogene Rhythmen fortwährend synchronisieren. Bereits bei Feten können circadiane Rhythmen, getriggert durch die Mutter, beobachtet werden. Nach der Geburt muss sich diese „innere Uhr“ in Synchronisation mit den externen Zeitgebern erst wieder neu einstellen. Frühgeborene sind in den ersten Lebenstagen zudem oft unausweichlichen Stressfaktoren durch intensivmedizinische, diagnostische, therapeutische oder pflegerische Maßnahmen ausgesetzt. Über die Entwicklung von circadianen Rhythmen bei Frühgeborenen gibt es in der Literatur bislang nur wenige und teilweise widersprüchliche Daten. In der vorliegenden Studie wurde bei Frühgeborenen die Reifung des endogenen Rhythmus bezüglich des Aktivitäts-Ruhe-Verhaltens und der Cortisolkonzentration im Speichel in den ersten Lebenswochen untersucht. Methodik: 62 Frühgeborene mit einem Gestationsalter von 30<37 SSW und einem postnatalen Alter <10 Lebenstagen wurden in die Studie eingeschlossen. An den Studientagen 1, 7 und 14 wurde bei allen Studienkindern über 24 Stunden das Aktivitäts-Ruhe-Verhalten mit Hilfe eines Aktometers aufgezeichnet. Bei 22 dieser Frühgeborenen wurden zusätzlich an den drei genannten Studientagen zu je sieben standardisierten Zeitpunkten Speichelproben für die Bestimmung (ELISA) der Cortisolkonzentration entnommen. Die Berechnung der Tag-Nacht-Rhythmik erfolgte mittels der Lomb-Scargle-Methode (Least Squares Spectral Analysis (LSSA)) und die Auswertung der Daten anhand eines angepassten linear gemischten Modells. Ergebnisse: Eine circadiane Rhythmik bezüglich des Hormons Cortisol konnte nur bei einem Frühgeborenen am ersten Studientag beobachtet werden. Ansonsten ließ sich weder ein circadianer noch ultradianer Rhythmus der Cortisolkonzentration erkennen. Am ersten Studientag war die Cortisolkonzentration im Mittel des gesamten Tages (= 24 Std.) signifikant (p < 0,05) höher als an den darauffolgenden Studientagen (Gesamttag 1: Median=16,5 nmol/L, Gesamttag 7: Median=9,8 nmol/L; Gesamttag 14: Median=10,0 nmol/L). Besonders die nächtliche Cortisolkonzentration der Frühgeborenen reduzierte sich signifikant (p < 0,05) im Studienverlauf (Nacht 1: Median=17,1 nmol/L; Nacht 7: Median=9,6 nmol/L; Nacht 14: Median=9,8 nmol/L). Das Aktivitäts-Ruhe-Verhalten der Frühgeborenen wurde durch einen ultradianen Rhythmus mit einer vierstündigen Periodenlänge in den ersten Lebenswochen dominiert. Bei 12 Kindern konnte an einzelnen Studientagen eine circadiane Periodenlänge beobachtet werden. Die Aktivitätsanalyse zeigte eine signifikante Zunahme des prozentualen Anteils von Ruhephasen während der ersten Lebenswochen (p < 0,05) (Tag 1: 55%; Tag 7: 61%; Tag 14: 60%). Die durchschnittliche Gesamtschlafzeit verlängerte sich signifikant (p < 0,05) von 66% an Studientag 1 auf 72% an Studientag 7. Schlussfolgerung: In den ersten vier Lebenswochen konnte bei den Frühgeborenen noch keine stabile circadiane Rhythmik gefunden werden. Hinsichtlich des Aktivitäts-Ruhe-Musters zeigte sich eine dominierende ultradiane Rhythmik von vier Stunden. Höhere Cortisolkonzentrationen und stärkere Aktivität der Frühgeborenen zu Beginn des Untersuchungszeitraumes sind möglicherweise auf stressreiche Umwelteinflüsse, wie z.B. intensivmedizinische Behandlungen oder medizinische Interventionen zurückzuführen. Weitere Studien sind in Bezug auf die Cortisolkonzentration und das Aktivitäts-Ruhe-Verhalten bei Frühgeborenen notwendig, um den Einfluss von wichtigen Umwelteinflüssen, wie Stressfaktoren und Krankheitsprozesse, aufzuzeigen sowie ggf. die Behandlung und Pflege optimieren zu können

Modulation der Hypophysen-Nebennierenrinde und Induktion von Apoptose an der adrenocorticalen Tumorzelle durch Oncostatin M

Diese Arbeit konnte Oncostatin M als Modulator der Hypothalamus-Hypophysen-Nebennierenrinden-Achse näher charakterisieren. Es konnte gezeigt werden, dass Oncostatin M an hypophysärem Gewebe über den gp130/LIFR-Komplex zur Aktivierung der Jak-STAT-Kaskade mit folgender STAT-abhängiger POMC- und STAT3-Expression und schließlich zur ACTH-Ausschüttung führt. Da über den gp130/OSMR-Rezeptorkomplex keine Jak-STAT-Aktivierung mit konsekutiver POMC- und STAT3-Expression und ACTH-Sekretion nachgewiesen werden konnte, wird postuliert, dass Oncostatin M an der Modulation der corticotrophen Funktion über den gp130/LIFR-Komplex, nicht jedoch über den gp130/OSMR-Komplex beteiligt ist. Auf adrenocorticaler Zellebene konnte erstmals ein direkter stimulierender Effekt von Oncostatin M auf die Steroidsekretion gezeigt werden. Murines OSM führt über den gp130/OSMR-Rezeptor-Komplex, humanes OSM und murines LIF zur Aktivierung der Jak-STAT-Kaskade und zur Steroidausschüttung durch murine Y-1 Zellen. Damit konnte Onostatin M als potenter Modulator der adrenocorticalen Zellfunktion charakterisiert werden. Erstmals wurde hier die Induktion von Apoptose durch OSM an adrenocorticalen Tumorzellen beschrieben. Es bleibt zu zeigen, dass der an der murinen Zelllinie Y-1 nachgewiesen Effekt auch auf humane Tumorzellen übertragbar ist. Ein zellspezifischer apoptotischer Effekt von OSM auf adrenocorticale Tumorzellen könnte ein potentieller wertvoller Mechanismus zur Entwicklung einer spezifischen Therapie des hochmalignen Nebennierenrindencarcinoms darstellen

Endovascular treatment of basilar tip aneurysms in the era of endosaccular flow disruption: a comparative study

PURPOSE This study aims to compare endosaccular flow disruptor (EFD) for treatment of basilar tip aneurysm (BTA) with coiling in terms of safety and efficacy. METHODS We retrospectively reviewed patients treated with an EFD for BTAs at our institution between 2013 and 2019 to standard coiling from the same period (control group). Patient demographics, aneurysm characteristics, procedural data, complications and clinical and angiographic outcome were compared between groups. RESULTS Twenty-three (56%) patients were treated with an EFD and eighteen (44%) patients were treated with coiling. Average aneurysm size was 8~mm in the EFD group and 6.9~mm in the coiling group, respectively (P = 0.2). Average fluoroscopy time, treatment DAP and air kerma were 33~min, 76 Gycm2 and 1.7~Gy in the EFD group and 81~min, 152 Gycm2 and 3.8~Gy in the coiling group, respectively (P < 0.001). In the EFD group, clinically relevant thromboembolic complications occurred in one patient (4%) vs. in 5 patients (28%) in the coiling group (P = 0.07). In each group, 4 patients had an unfavourable outcome at discharge (P = 0.7). Adequate occlusion rates were 96% in the EFD group and 100% and coiling group. Six (26%) patients were prescribed long-term antiplatelet therapy in the EFD group vs. eleven (61%) patients in the coiling group (P = 0.02). CONCLUSION Both treatment concepts provided similar technical success and safety. However, procedure time, radiation exposure and a need for long-term antiaggregation were lower with EFD

Zeitwohlstand für Pflegekräfte als Potenzial für eine nachhaltige Gesellschaft

Seit vielen Jahren steht die Überlastung des Gesundheitssystems und insbesondere der Pflege in der Kritik. Zunehmend rücken auch die damit zusammenhängenden ökologischen Auswirkungen in den Fokus. Welche konkreten Maßnahmen gibt es, die den Zeitdruck des Personals im Gesundheitsbereich reduzieren und damit Potenziale für eine nachhaltige Lebensführung bieten

Safety and efficacy of the Derivo Embolization Device for the treatment of unruptured intracranial aneurysms: a multicentric study

Background The Derivo Embolization Device (DED) is a novel flow diverter stent that provides increased x-ray visibility, an improved delivery system, and potentially reduced thrombogenicity. The objective of this study was to evaluate the early safety and efficacy of the second-generation DED. Methods We retrospectively analyzed all patients with unruptured intracranial aneurysms (UIAs) treated with the DED between November 2015 and December 2017 in three German tertiary care centers. Procedural details, complications, and morbidity within 30 days after treatment, as well as the aneurysm occlusion rates after 6 months (O'Kelly-Marotta scale, OKM), were evaluated. Results Implantation of the DED was attempted in 42 patients with 42 aneurysms. All procedures were technically successful. Multiple DEDs were used in three aneurysms (7.2%) and adjunctive coiling in 11 (26.2%). Procedure-related complications occurred in four cases (9.5%) including three thromboembolic events and one aneurysm perforation. The morbidity rate was 2.4% and there was no mortality. One patient suffered an ischemic stroke with persistent aphasia at 30-day follow-up due to a thromboembolic infarct (modified Rankin Scale score 1). Among 33 patients (78.6%) available for angiographic follow-up, complete (OKM D) and favorable (OKM C+D) aneurysm occlusion was obtained in 72.7% (24/33) and 87.9% (29/33), respectively. Conclusions Endovascular treatment of UIAs with the DED is associated with high procedural safety and adequate occlusion rates. Examinations at 1- and 2-year follow-up will provide data on the long-term safety and angiographic outcomes of this device

Childhood haemorrhagic stroke: a 7-year single-centre experience

Background In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS). Objective The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS. Design We performed a retrospective analysis of electronic medical records of children (28 days-18 years) diagnosed with HS between 2010 and 2016. Results We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home. Conclusions HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors ('mono-risk' disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy

Endovascular stroke treatment in orally anticoagulated patients: an analysis from the German Stroke Registry-Endovascular Treatment

Background Endovascular treatment (ET) in orally anticoagulated (OAC) patients has not been evaluated in randomized clinical trials and data regarding this issue are sparse. Methods We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET; NCT03356392, date of registration: 22 Nov 2017). The primary outcomes were successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI 2b-3), good outcome at 3 months (modified Rankin scale [mRS] 0–2 or back to baseline), and intracranial hemorrhage (ICH) on follow-up imaging at 24 h analyzed by unadjusted univariate and adjusted binary logistic regression analysis. Additionally, we analyzed mortality at 3 months with adjusted binary logistic regression analysis. Results Out of 6173 patients, there were 1306 (21.2%) OAC patients, 479 (7.8%) with vitamin K antagonists (VKA) and 827 (13.4%) with non-vitamin K antagonist oral anticoagulation (NOAC). The control group consisted of 4867 (78.8%) non-OAC patients. ET efficacy with the rates of mTICI 2b-3 was similar among the three groups (85.6%, 85.3% vs 84.3%, p = 0.93 and 1). On day 90, good outcome was less frequent in OAC patients (27.8%, 27.9% vs 39.5%, p < 0.005 and < 0.005). OAC status was not associated with ICH at 24 h (NOAC: odd’s ratio [OR] 0.89, 95% confidence interval [CI] 0.67–1.20; VKA: OR 1.04, CI 0.75–1.46). Binary logistic regression analysis revealed no influence of OAC status on good outcome at 3 months (NOAC: OR 1.25, CI 0.99–1.59; VKA: OR 1.18, CI 0.89–1.56) and mortality at 3 months (NOAC: OR 1.03, CI 0.81–1.30; VKA: OR 1.04, CI 0.78–1.1.37). Conclusions ET can be performed safely and successfully in LVO stroke patients treated with OAC. Clinical trial registration-URL http://www.clinicaltrials.gov. Unique identifier: NCT03356392

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I

BACKGROUND Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. METHODS We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients' past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. RESULTS Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21-89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431-6.771) both on uni- and multivariate analysis. CONCLUSION Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence

Magnetic Resonance Imaging-Based Robotic Radiosurgery of Arteriovenous Malformations

Objective: CyberKnife offers CT- and MRI-based treatment planning without the need for stereotactically acquired DSA. The literature on CyberKnife treatment of cerebral AVMs is sparse. Here, a large series focusing on cerebral AVMs treated by the frameless CyberKnife stereotactic radiosurgery (SRS) system was analyzed. Methods: In this retrospective study, patients with cerebral AVMs treated by CyberKnife SRS between 2005 and 2019 were included. Planning was MRI- and CT-based. Conventional DSA was not coregistered to the MRI and CT scans used for treatment planning and was only used as an adjunct. Obliteration dynamics and clinical outcome were analyzed. Results: 215 patients were included. 53.0% received SRS as first treatment; the rest underwent previous surgery, embolization, SRS, or a combination. Most AVMs were classified as Spetzler-Martin grade I to III (54.9%). Hemorrhage before treatment occurred in 46.0%. Patients suffered from headache (28.8%), and seizures (14.0%) in the majority of cases. The median SRS dose was 18 Gy and the median target volume was 2.4 cm³. New neurological deficits occurred in 5.1% after SRS, with all but one patient recovering. The yearly post-SRS hemorrhage incidence was 1.3%. In 152 patients who were followed-up for at least three years, 47.4% showed complete AVM obliteration within this period. Cox regression analysis revealed Spetzler-Martin grade (P = 0.006) to be the only independent predictor of complete obliteration. Conclusions: Although data on radiotherapy of AVMs is available, this is one of the largest series, focusing exclusively on CyberKnife treatment. Safety and efficacy compared favorably to frame-based systems. Non-invasive treatment planning, with a frameless SRS robotic system might provide higher patient comfort, a less invasive treatment option, and lower radiation exposure

General anesthesia versus conscious sedation in mechanical thrombectomy

BACKGROUND AND PURPOSE Anesthesia regimen in patients undergoing mechanical thrombectomy (MT) is still an unresolved issue. METHODS We compared the effect of anesthesia regimen using data from the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2019. Degree of disability was rated by the modified Rankin Scale (mRS), and good outcome was defined as mRS 0-2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction scale was 2b-3. RESULTS Out of 6,635 patients, 67.1% (n=4,453) patients underwent general anesthesia (GA), 24.9% (n=1,650) conscious sedation (CS), and 3.3% (n=219) conversion from CS to GA. Rate of successful reperfusion was similar across all three groups (83.0% vs. 84.2% vs. 82.6%, P=0.149). Compared to the CA-group, the GA-group had a delay from admission to groin (71.0 minutes vs. 61.0 minutes, P\textless0.001), but a comparable interval from groin to flow restoration (41.0 minutes vs. 39.0 minutes). The CS-group had the lowest rate of periprocedural complications (15.0% vs. 21.0% vs. 28.3%, P\textless0.001). The CS-group was more likely to have a good outcome at follow-up (42.1% vs. 34.2% vs. 33.5%, P\textless0.001) and a lower mortality rate (23.4% vs. 34.2% vs. 26.0%, P\textless0.001). In multivariable analysis, GA was associated with reduced achievement of good functional outcome (odds ratio OR, 0.82; 95{\%} confidence interval CI, 0.71 to 0.94; P=0.004) and increased mortality (OR, 1.42; 95{\%} CI, 1.23 to 1.64; P{\textless}0.001). Subgroup analysis for anterior circulation strokes (n=5,808) showed comparable results. CONCLUSIONS We provide further evidence that CS during MT has advantages over GA in terms of complications, time intervals, and functional outcome