Akustikusneurinome: Eine Studie zum Einfluss verschiedener Operationsprinzipien auf die Behandlungsmorbidität – Postoperative Liquorfisteln und die Funktion des Nervus Facialis

In retrospektiv angelegten Untersuchungen soll der Einfluss unterschiedlicher Operationsstrategien auf die Morbidität bei der Behandlung des Akustikusneurinoms aufgezeigt werden. In einer ersten Untersuchung wurde der Einfluss eines doppelten Verschlusses der Dura mater nach subokzipitaler Kraniotomie zur mikrochirurgischen Exstirpation eines Akustikusneurinoms im Hinblick auf die Vermeidung einer Liquorfistel analysiert. Hier wurden zwei Patientengruppen miteinander verglichen. Zum einen Patienten mit einem einfachen Duraverschluss, Duranaht plus alloplastisches Material epidural. Zum anderen Patienten mit einem doppelten Duraverschluss. Hier epidurales und subdurales alloplastisches Material plus Duranaht. Untersucht wurden das Auftreten von Liquorfisteln sowie die Häufigkeit von Wundheilungsstörungen. Es konnte keine signifikante Überlegenheit einer Operationstechnik zur Vermeidung von postoperativen Liquorfisteln gezeigt werden. In einer zweiten Untersuchung wurde der Zusammenhang einer inkompletten Resektion des Tumors (Belassen eines Kapselrestes) mit dem Ziel der Schonung des Nervus facialis untersucht. Hierzu wurden die postoperative Facialisfunktion sowie ein möglicherweise erhöhtes Rezidivrisiko im Verlauf betrachtet. Die postoperative Funktion des N. facialis wurde zwischen den Patientengruppen mit Kapselrest (inkomplette Entfernung) und ohne Kapselrest (komplette Entfernung) verglichen. Es zeigte sich bei vergleichbarer postoperativer Facialisfunktion kein signifikanter Unterschied im Auftreten von Rezidiven nach inkompletter Resektion. Nur gut ein Drittel der inkomplett resezierten Tumore zeigten im Nachbeobachtungszeitraum (im Mittel 52 Monate) überhaupt ein Wachstum

Neurosurgical Care during the COVID-19 Pandemic in Central Germany: A Retrospective Single Center Study of the Second Wave

The healthcare system has been placed under an enormous burden by the SARS-CoV-2 (COVID-19) pandemic. In addition to the challenge of providing sufficient care for COVID-19 patients, there is also a need to ensure adequate care for non-COVID-19 patients. We investigated neurosurgical care in a university hospital during the pandemic. We examined the second wave of the pandemic from 1 October 2020 to 15 March 2021 in this retrospective single-center study and compared it to a pre-pandemic period from 1 October 2019 to 15 March 2020. Any neurosurgical intervention, along with patient- and treatment-dependent factors, were recorded. We also examined perioperative complications and unplanned readmissions. A statistical comparison of the study groups was performed. We treated 535 patients with a total of 602 neurosurgical surgeries during the pandemic. This compares to 602 patients with 717 surgeries during the pre-pandemic period. There were 67 fewer patients (reduction to 88.87%) admitted and 115 fewer surgeries (reduction to 83.96%) performed, which were essentially highly elective procedures, such as cervical spinal stenosis, intracranial neurinomas, and peripheral nerve lesions. Regarding complication rates and unplanned readmissions, there was no significant difference between the COVID-19 pandemic and the non-pandemic patient group. Operative capacities were slightly reduced to 88% due to the pandemic. Nevertheless, comprehensive emergency and elective care was guaranteed in our university hospital. This speaks for the sufficient resources and high-quality processes that existed even before the pandemic

The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients

Background: IDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients. Methods: The records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value. Results: One hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p < 0.001), and neurological deterioration during follow-up (HR 1.38, p < 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p < 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points. Conclusion: Neurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM

Endovascular Treatment of Intracranial Aneurysms in Small Peripheral Vessel Segments—Efficacy and Intermediate Follow-Up Results of Flow Diversion With the Silk Vista Baby Low-Profile Flow Diverter

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events. Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O’Kelly Marotta (OKM) grading system. Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1–B3 and A2–A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery. Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events

Cortisol excess in patients with primary aldosteronism impacts on left ventricular hypertrophy

Context Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared to matched essential hypertensives. In recent studies frequent co-secretion of cortisol and aldosterone has been reported in PA patients. Objective Our aim was to investigate the impact of cortisol co-secretion on left ventricular hypertrophy in PA patients. We determined 24-h excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and one year after initiation of treatment for PA. Patients We included 73 patients from the Munich center of the German Conn's registry; 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. Results At the time of diagnosis, 85% of PA patients showed left ventricular hypertrophy according to left ventricular mass index (LVMI, median 62.4 g/m2.). LVMI correlated positively with total glucocorticoid excretion (r2=0.076, p=0.018) as well as with tetrahydroaldosterone excretion (r2=0.070, p=0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (p<0.001) while mineralocorticoid receptor antagonist therapy in bilateral adrenal hyperplasia patients reduced LVMI to a lesser degree (p=0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Conclusion Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion

Urine steroid metabolomics as a diagnostic tool in primary aldosteronism

Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs.</p

Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID mice

More effective treatment of metastasizing osteosarcoma with a current mean 5-year survival rate of less than 20% requires more detailed knowledge on mechanisms and key regulatory molecules of the complex metastatic process. CXCR4, the receptor of the chemokine CXCL12, has been reported to promote tumor progression and metastasis in osteosarcoma. CXCR7 is a recently deorphanized CXCL12-scavenging receptor with so far not well-defined functions in tumor biology. The present study focused on a potential malignancy enhancing function of CXCR7 in interaction with CXCR4 in osteosarcoma, which was investigated in an intratibial osteosarcoma model in SCID mice, making use of the human 143B osteosarcoma cell line that spontaneously metastasizes to the lung and expresses endogenous CXCR4. 143B osteosarcoma cells stably expressing LacZ (143B-LacZ cells) were retrovirally transduced with a gene encoding HA-tagged CXCR7 (143B-LacZ-X7-HA cells). 143B-LacZ-X7-HA cells coexpressing CXCR7 and CXCR4 exhibited CXCL12 scavenging and enhanced adhesion to IL-1β-activated HUVEC cells compared to 143B-LacZ cells expressing CXCR4 alone. SCID mice intratibially injected with 143B-LacZ-X7-HA cells had significantly (p<0.05) smaller primary tumors, but significantly (p<0.05) higher numbers of lung metastases than mice injected with 143B-LacZ cells. Unexpectedly, 143B-LacZ-X7-HA cells, unlike 143B-LacZ cells, also metastasized with high incidence to the auriculum cordis. In conclusion, expression of the CXCL12 scavenging receptor CXCR7 in the CXCR4-expressing human 143B osteosarcoma cell line enhances its metastatic activity in intratibial primary tumors in SCID mice that predominantly metastasize to the lung and thereby closely mimic the human disease. These findings point to CXCR7 as a target, complementary to previously proposed CXCR4, for more effective metastasis-suppressive treatment in osteosarcoma

Segment Occlusion vs. Reconstruction—A Single Center Experience With Endovascular Strategies for Ruptured Vertebrobasilar Dissecting Aneurysms

Objective: Ruptured dissecting aneurysms of the intracranial vertebral arteries exhibit an extraordinarily high risk for morbidity and mortality and are prone to re-rupture. Therefore, early treatment is mandatory to induce stagnation of the critical dynamic mural process. Appropriate endovascular approaches are segment sacrifice and reconstruction, however, both carry specific risks and benefits. To date most studies discuss only one of these approaches and focus on one specific device or technique. Therefore, our study aimed to present our experiences with both techniques, providing a considered approach on when to perform endovascular reconstruction or sacrifice.Materials and Methods: We retrospectively reviewed patients with subarachnoid hemorrhage in our database, suffering from dissecting aneurysms of the intradural vertebral arteries and treated endovascularly in the acute setting. A total of 16 cases were included. Clinical history, radiologic findings and outcomes were analyzed.Results: In 7 patients a reconstructive approach was chosen with 4 of them receiving stent-assisted coiling as primary strategy. One of the 7 patients suffered early re-bleeding due to progression of the dissection and therefore treatment was augmented with implantation of 2 flow diverters. The remaining 2 patients were primarily treated with flow diverters in telescoping technique. In 9 patients a deconstructive approach was followed: 6 patients were treated with proximal coil-occlusion of the V4 segment, 3 patients received distal coiling of the V4 segment. Two patients died (GOS 1) in the subacute stage due to sequelae of recurrent episodes of raised intracranial pressure and parenchymal hemorrhage. Two patients kept severe disability (GOS 3), six patients had moderate disability (GOS 4) and seven patients showed full recovery (GOS 5). None of the patients suffered from a procedural or postprocedural ischemic stroke.Conclusions: In patients with good collateral vascularization, proximal, or distal partial segment sacrifice via with endovascular coil occlusion seems to yield the best risk-benefit ratio for treatment of ruptured dissecting V4 aneurysms, especially since no continued anticoagulation is required and possibly essential surgery remains feasible in this scenario. If possible, PICA occlusion should be avoided—although even proximal PICA occlusion can become necessary, when weighing against the risk of an otherwise untreated ruptured V4 dissecting aneurysm. Contrarily, if the dominant V4 segment is affected, the hemodynamic asymmetry prohibits occlusion and necessitates reconstruction of the respective segment. For this, implants with high metal coverage treating the entire affected segment appear to be the most promising approach

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10−5) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10−5, ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutatio