Expression of Wnt genes in human breast cancer cell lines and tumor-associated macrophages

Die Interaktion zwischen Tumorzellen und Stromazellen spielt eine wichtige Rolle für die lokale Tumorprogression, die Invasivität und Metastasierung von soliden Tumoren wie dem Mammakarzinom. Es ist bekannt, dass die Kokultivierung von MCF-7 Mammakarzinomzellen mit humanen Makrophagen zu einer Wnt5a abhängigen Invasivitätssteigerung der Mammkarzinomzellen führt, welche durch den Wnt-Antagonisten Dkk-1 verhindert werden kann. Unbekannt war, ob sich primär hoch invasive Mammakarzinomzellen wie etwa die tripe-negative (TN) Mammakarzinomzelllinie MDA-MB-231 und die schwach invasive Zelllinie MCF-7 hinsichtlich ihrer Expression von Wnt- und Wnt-abhängigen Genen unterscheiden. So zeigten sich sowohl die nicht-kanonischen Wnt-Liganden Wnt5a und Wnt5b als auch die Wnt-assoziierten Gene VEGF-A und PLAU-R in der MDA-MB-231 Zelllinie als deutlich höher exprimiert im Vergleich zu MCF-7. Insbesondere die Expressionsunterschiede von Wnt5a und Wnt5b waren zuvor unbekannt und erweitern die molekulare Charakteristik dieser Zelllinien. In Kokulturexperimten von MCF-7 Mammakarzinomzellen und humanen Makrophagen zeigte sich in dieser Arbeit eine signifkant höhere Expression von Wnt5a, VEGF-A und TNF-α in MCF-7 nach 24h. Dies ist ein weiterer Aspekt für die molekularen Mechanismen, welche zu einer Invasivitätssteigerung solider Tumore durch Tumor-assoziierte Makrophagen (TAM) führen können. Interessanterweise blieb diese Regulation unter Zugabe von rh Dkk-1 aus, was eine wichtige Rolle von Dkk-1 möglicherweise auch aus therapeutischer Sicht nahelegt

The impact of endovascular rescue therapy on the clinical and radiological outcome after aneurysmal subarachnoid hemorrhage: a safe and effective treatment option for hemodynamically relevant vasospasm?

OBJECTIVE: Cerebral vasospasm (CVS) represents one of the multiple contributors to delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Especially the management of CVS, refractory to medical treatment, is a challenging task during the acute phase after aSAH. Endovascular rescue therapies (ERT), such as medical and mechanical dilation, are possible treatment options on an individual basis. However, data about the influence on the patients' functional outcomes are limited. This study aims to assess the impact of ERT on the long-term functional outcome in aSAH-patients with refractory CVS. METHODS: We performed a retrospective analysis of aSAH patients treated between 2012 and 2018. CVS was considered refractory, if it persisted despite oral/intravenous nimodipine application and induced hypertension. The decision to perform ETR was made on an individual basis, according to the detection of “tissue at risk” on computed tomography perfusion (CTP) scans and CVS on computed tomography angiography (CTA) or digital subtraction angiography (DSA). The functional outcome was assessed according to the modified Rankin scale (mRS) 3 months after the ictus, whereas an mRS ≤ 2 was considered as a good outcome. RESULTS: A total of 268 patients were included. Out of these, 205 patients (76.5%) were treated without ERT (group 1) and 63 patients (23.5%) with ERT (group 2). In 20 patients (31.8%) balloon dilatation was performed, in 23 patients (36.5%) intra-arterial nimodipine injection alone, and in 20 patients (31.8%) both procedures were combined. Considering only the patient group with DCI, the patients who were treated with ERT had a significantly better outcome compared to the patients without ERT (Mann–Whitney test, p = 0.02). CONCLUSION: Endovascular rescue therapies resulted in a significantly better functional outcome in patients with DCI compared to the patient group treated without ETR. CTP and CTA-based identification of “tissue at risk” might be a reliable tool for patient selection for performing ERT

Fully Reversible Contrast-Induced Encephalopathy Mimicking Stroke after Flow Diverter Treatment of Carotid Cave Aneurysm

Contrast-induced encephalopathy (CIE) is a rare complication of coronary and neurointerventional procedures. The condition is believed to arise from endothelial damage secondary to exposure to iodinated contrast media. A wide spectrum of clinical manifestations has been reported including seizures, cortical blindness, and focal neurological deficits. This report details the case of fully reversible CIE mimicking severe anterior circulation stroke in a 55-year-old female following elective endovascular treatment with a flow diverter of a carotid cave aneurysm. The patient was managed conservatively with intravenous hydration and steroids and showed an excellent prognosis with supportive management

Automated brain segmentation and volumetry in dementia diagnostics: a narrative review with emphasis on FreeSurfer

BackgroundDementia can be caused by numerous different diseases that present variable clinical courses and reveal multiple patterns of brain atrophy, making its accurate early diagnosis by conventional examinative means challenging. Although highly accurate and powerful, magnetic resonance imaging (MRI) currently plays only a supportive role in dementia diagnosis, largely due to the enormous volume and diversity of data it generates. AI-based software solutions/algorithms that can perform automated segmentation and volumetry analyses of MRI data are being increasingly used to address this issue. Numerous commercial and non-commercial software solutions for automated brain segmentation and volumetry exist, with FreeSurfer being the most frequently used.ObjectivesThis Review is an account of the current situation regarding the application of automated brain segmentation and volumetry to dementia diagnosis.MethodsWe performed a PubMed search for “FreeSurfer AND Dementia” and obtained 493 results. Based on these search results, we conducted an in-depth source analysis to identify additional publications, software tools, and methods. Studies were analyzed for design, patient collective, and for statistical evaluation (mathematical methods, correlations).ResultsIn the studies identified, the main diseases and cohorts represented were Alzheimer’s disease (n = 276), mild cognitive impairment (n = 157), frontotemporal dementia (n = 34), Parkinson’s disease (n = 29), dementia with Lewy bodies (n = 20), and healthy controls (n = 356). The findings and methods of a selection of the studies identified were summarized and discussed.ConclusionOur evaluation showed that, while a large number of studies and software solutions are available, many diseases are underrepresented in terms of their incidence. There is therefore plenty of scope for targeted research

Angioplasty with the scepter C dual lumen balloon catheter and postprocedural result evaluation in patients with subarachnoid hemorrhage related vasospasms

Open-Access-Publikationsfonds 202

Endoscope-enhanced fluorescence-guided microsurgery increases survival in patients with glioblastoma

Abstract Purpose Extent of resection (EOR) predicts progression-free survival (PFS) and may impact overall survival (OS) in patients with glioblastoma. We recently demonstrated that 5-aminolevulinic acid-(5-ALA)-fluorescence-enhanced endoscopic surgery increase the rate of gross total resection. However, it is hitherto unknown whether fluorescence-enhanced endoscopic resection affects survival. Methods We conducted a retrospective single-center analysis of a consecutive series of patients who underwent surgery for non-eloquently located glioblastoma between 2011 and 2018. All patients underwent fluorescence-guided microscopic or fluorescence-guided combined microscopic and endoscopic resection. PFS, OS, EOR as well as clinical and demographic parameters, adjuvant treatment modalities, and molecular characteristics were compared between microscopy-only vs. endoscopy-assisted microsurgical resection. Results Out of 114 patients, 73 (65%) were male, and 57 (50%) were older than 65 years. Twenty patients (18%) were operated on using additional endoscopic assistance. Both cohorts were equally distributed in terms of age, performance status, lesion location, adjuvant treatment modalities, and molecular status. Gross total resection was achieved in all endoscopy-assisted patients compared to about three-quarters of microscope-only patients (100% vs. 75.9%, p =0.003). The PFS in the endoscope-assisted cohort was 19.3 months (CI95% 10.8–27.7) vs. 10.8 months (CI95% 8.2–13.4; p =0.012) in the microscope-only cohort. OS in the endoscope-assisted group was 28.9 months (CI95% 20.4–34.1) compared to 16.8 months (CI95% 14.0–20.9), in the microscope-only group ( p =0.001). Conclusion Endoscope-assisted fluorescence-guided resection of glioblastoma appears to substantially enhance gross total resection and OS. The strong effect size observed herein is contrasted by the limitations in study design. Therefore, prospective validation is required before we can generalize our findings

Venous Sinus Stenting Alone as an Effective Treatment for Complex Dural Arteriovenous Fistulas with Sinus Thrombosis

Dural arteriovenous fistulas (dAVFs) are rare vascular malformations, often complicated by sinus thrombosis and cortical reflux. We report a patient with a Cognard Type IIb dAVF at the right transverse sinus and ipsilateral sigmoid sinus thrombosis, unsuitable for conventional embolization due to contralateral sinus hypoplasia. A novel therapeutic approach involving direct jugular vein puncture, venous recanalization, and stenting using a stiff 0.035-inch guidewire effectively downgraded the dAVF to Cognard Type I. At 3-month follow-up, stable angiographic outcomes, marked clinical improvement, and absence of seizures confirmed the efficacy of sinus stenting as a standalone treatment in an anatomically challenging case

One-Stop Management of 230 Consecutive Acute Stroke Patients: Report of Procedural Times and Clinical Outcome.

BACKGROUND AND PURPOSE: Rapid thrombectomy for acute ischemic stroke caused by large vessel occlusion leads to improved outcome. Optimizing intrahospital management might diminish treatment delays. To examine if one-stop management reduces intrahospital treatment delays and improves functional outcome of acute stroke patients with large vessel occlusion. METHODS: We performed a single center, observational study from June 2016 to November 2018. Imaging was acquired with the latest generation angiography suite at a comprehensive stroke center. Two-hundred-thirty consecutive adults with suspected acute stroke presenting within 6 h after symptom onset with a moderate to severe National Institutes of Health Stroke Scale (≥10 in 2016; ≥7 since January 2017) were directly transported to the angiography suite by bypassing multidetector CT. Noncontrast flat-detector CT and biphasic flat-detector CT angiography were acquired with an angiography system. In case of a large vessel occlusion patients remained in the angiography suite, received intravenous rtPA therapy and underwent thrombectomy. As primary endpoints, door-to-reperfusion times and functional outcome at 90 days were recorded and compared in a case-control analysis with matched prior patients receiving standard management. RESULTS: A total of 230 patients (123 women, median age of 78 years (Interquartile Range (IQR) 69-84)) were included. Median symptom-to-door time was 130 min (IQR 70-195). Large vessel occlusion was diagnosed in 166/230 (72%) patients; 64/230 (28%) had conditions not suitable for thrombectomy. Median door-to-reperfusion time for M1 occlusions was 64 min (IQR 56-87). Compared to 43 case-matched patients triaged with multidetector CT, median door-to-reperfusion time was reduced from 102 (IQR 85-117) to 68 min (IQR 53-89; p < 0.001). Rate of good functional outcome was significantly better in the one-stop management group (p = 0.029). Safety parameters (mortality, sICH, any hemorrhage) did not differ significantly between groups. CONCLUSIONS: One-stop management for stroke triage reduces intrahospital time delays in our specific hospital setting

Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies—an observational proof-of-concept study

Background: Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology. Methods: As a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology. Results: In 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p < 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p < 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p < 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p > 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI. Conclusion: Risk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual’s risk of bleeding