Perioperative Funktionsdiagnostik der Sprache und Motorik mittels transkranieller Magnetstimulation

Durch die steigende medizinische Technisierung finden neuartige Diagnostika zunehmend Anwendung in den operativen Fachbereichen. Aufgrund der Diversität dieser technischen Mittel ist ein fundiertes Wissen über ihre Grundlagen, Interpretationsmöglichkeiten und jeweilige Präzision unabdingbar. Insbesondere in der Chirurgie hirneigener Tumore besteht eine Diskrepanz zwischen der Notwendigkeit, eine möglichst vollständige Resektion zu erreichen, um eine Verlängerung der Gesamtüberlebenszeit zu erzielen, ohne andererseits eine frühe Beeinträchtigung umgebener eloquenter Strukturen zu verursachen. Dies gilt neben lebenswichtigen Bereichen wie der Hirnstammregion, insbesondere für die Funktionen der Sprache und Motorik, deren Schädigung mit einer erheblichen Beeinträchtigung der Lebensqualität einhergeht. Durch die Läsions-bedingte Verschiebung anatomischer Areale ist eine dezidierte und individuelle Darstellung dieser Bereiche elementar. Die transkranielle Magnetstimulation (TMS) bietet, als nicht-invasives Diagnostikum, eine Kartierungsmöglichkeit eloquenter Funktionen und zeigt hierbei eine hohe Präzision im Vergleich zu der als Goldstandard geltenden Direkten Corticalen Stimulation (DCS). Methodik: Nach Erhebung der Ruhemotorschwelle erfolgt in den ersten beiden Studien eine TMS-gekoppelte kartographische Darstellung sprach-eloquenter Areale, bei Patienten mit linkshemisphärischen, intrinsischen Tumoren im Bereich der Sylvischen Fissur. Diese Kartierung wird in der ersten Studie mit der einer gesunden Vergleichskohorte und in der zweiten Studie mit den Resultaten der direkten Cortexstimulation korreliert und statistisch evaluiert. In der dritten Studie wird der zentralmotorische Cortex mit seinen assoziierten Faserbahnen nTMS-basiert dargestellt. Weiterhin wird der Einfluss diverser Variablen auf die Entstehung eines postoperativen motorischen Defizits analysiert. Ergebnisse: Die Resultate der ersten Studie zeigen, insbesondere in der Probandengruppe, eine hohe Sensitivität der repetitiven navigierten TMS für Sprachfunktion im Bereich des klassischen Broca-Areals und implizieren eine zunehmende Beteiligung rechtshemisphärischer Cortexareale bei Patienten mit linksseitigen perisylvischen Läsionen. Die zweite Studie bestätigt das Induktionspotential der TMS für diverse Sprachfehler, wobei insbesondere in anterioren Sprachregionen, wie dem frontalen Operculum, ein hoher negativer prädiktiver Wert im Vergleich zur direkten Cortexstimulation gezeigt werden konnte. Die dritten Studienergebnisse bestätigen die hohe Genauigkeit der TMS für die Visualisierung primärmotorischer Areale und demonstrieren einen prognostischen Stellenwert der Ruhemotorschwelle für die Entstehungswahrscheinlichkeit eines postoperativen Motordefizits in der Meningeomchirurgie. Zusammenfassung: Die TMS eignet sich als nebenwirkungsarmes, präzises und nicht-invasives Diagnostikum zur individuellen Repräsentation sprach- und motor-eloquenter Regionen und nimmt somit eine zentrale Rolle in der Risikostratifizierung und Operationsplanung neurochirurgischer Eingriffe ein.Due to the increase of medical technology, the integration of its technical instruments into the surgical field is on the rise. With a gaining amount of available tools, the exact knowledge of technical principles and their interpretation becomes mandatory. Particularly in neurosurgery a discrepancy between the need to achieve maximum resection to prolong overall survival, exists, in contrast to preserving functionality and avoiding a neurological impairment. This counts in particular for elementary neurological functions such as speech and movement. Disrupting these capacities has a lasting impact on the patients’ quality of life. Brain lesions can cause an alternation of anatomical landmarks and make their accurate identification challenging. Therefore, it is obligatory to be aware of the individual localisation of eloquent areas. Transcranial magnetic stimulation (TMS) enables a non-invasive visualization of the cortical representation of language and motor activity and demonstrates hereby a high reliability with regard to the gold standard of Direct Cortical Stimulation (DCS). Methods: After determining the resting motor threshold (RMT) in the first two studies, language mapping, with a TMS-triggered object-naming task, is carried out on patients with left-hemispheric lesions within the Sylvian Fissure, to identify speech eloquent areas and allocate them to their respective anatomical location. The first survey compares the obtained illustration of language to a group of healthy volunteers. The second draws a comparison to the cortical language representation, as registered using DCS. The third study uses nTMS to picture the motor pathway with its cortex and corticospinal tract. Followed by analysis of the predictive role of TMS on motor outcome. Results: The first study reveals a high sensitivity of rnTMS mapping on Broca’s classical speech area, which is particularly observed in healthy volunteers. Whereas an increased involvement of the right hemisphere in language processing becomes evident in patients with left sided perisylvian lesions. The second survey emphasises the TMS-capability of inducing speech disturbances primary in anterior language regions and its negative predictive value in correlation to DCS. The third study approves the precision of TMS-based motor mapping and identifies the RMT as an independent predictor for motor deficits in surgery for rolandic meningiomas. Conclusion: Our studies confirm TMS to be a safe, reliable and non-invasive tool on representing individual speech- and motor-eloquent areas. Herewith it demonstrates to be a useful instrument for risk stratification and the development of the surgical approach

Augmented reality visualization in brain lesions: a prospective randomized controlled evaluation of its potential and current limitations in navigated microneurosurgery

Background: Augmented reality (AR) has the potential to support complex neurosurgical interventions by including visual information seamlessly. This study examines intraoperative visualization parameters and clinical impact of AR in brain tumor surgery. Methods: Fifty-five intracranial lesions, operated either with AR-navigated microscope (n = 39) or conventional neuronavigation (n = 16) after randomization, have been included prospectively. Surgical resection time, duration/type/mode of AR, displayed objects (n, type), pointer-based navigation checks (n), usability of control, quality indicators, and overall surgical usefulness of AR have been assessed. Results: AR display has been used in 44.4% of resection time. Predominant AR type was navigation view (75.7%), followed by target volumes (20.1%). Predominant AR mode was picture-in-picture (PiP) (72.5%), followed by 23.3% overlay display. In 43.6% of cases, vision of important anatomical structures has been partially or entirely blocked by AR information. A total of 7.7% of cases used MRI navigation only, 30.8% used one, 23.1% used two, and 38.5% used three or more object segmentations in AR navigation. A total of 66.7% of surgeons found AR visualization helpful in the individual surgical case. AR depth information and accuracy have been rated acceptable (median 3.0 vs. median 5.0 in conventional neuronavigation). The mean utilization of the navigation pointer was 2.6 x /resection hour (AR) vs. 9.7 x /resection hour (neuronavigation); navigation effort was significantly reduced in AR (P < 0.001). Conclusions: The main benefit of HUD-based AR visualization in brain tumor surgery is the integrated continuous display allowing for pointer-less navigation. Navigation view (PiP) provides the highest usability while blocking the operative field less frequently. Visualization quality will benefit from improvements in registration accuracy and depth impression

BRAF inhibitor treatment of classical hairy cell leukemia allows successful vaccination against SARS-CoV-2

In classical hairy cell leukemia (HCL), standard treatments including purine analogs achieve a durable response (up to 90%), but lead to severe immunosuppression and long-lasting depletion of CD4 + T lymphocytes. The BRAF inhibitor vemurafenib is effective in HCL, but its use in first-line treatment is restricted to select clinical situations (e.g. active infection). Its impact on immune function or response to vaccines in HCL is unclear. We treated four HCL patients with vemurafenib during the COVID-19 pandemic and monitored immune reconstitution and response to SARS-CoV-2 immunization. All patients responded to HCL treatment with normalization of peripheral blood counts. No severe infections occurred. As an indication of limited immunosuppression by vemurafenib, stable CD4 + and CD8 + T lymphocyte counts and immunoglobulin levels were observed. Three out of four patients received SARS-CoV-2 vaccination (Pfizer-BioNTech) during treatment with vemurafenib. IgG antibody levels against the spike-protein of SARS-CoV-2 were detected (40-818 AE/ml). Our data suggest that vemurafenib has limited effects on cellular and humoral immune function in HCL, which allows for successful SARS-CoV-2 vaccination. These data support the use of BRAF inhibitors during the current pandemic where continued immune response is necessary for minimizing the COVID-19-related risk of non-vaccinated patients

Quantification of glyphosate and aminomethylphosphonic acid from microbiome reactor fluids

Rationale: Glyphosate is one of the most widely used herbicides and it is suspected to affect the intestinal microbiota through inhibition of aromatic amino acid synthesis via the shikimate pathway.In vitromicrobiome bioreactors are increasingly used as model systems to investigate effects on intestinal microbiota and consequently methods for the quantitation of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in microbiome model systems are required. Methods: An optimized protocol enables the analysis of both glyphosate and AMPA by simple extraction with methanol:acetonitrile:water (2:3:1) without further enrichment steps. Glyphosate and AMPA are separated by liquid chromatography on an amide column and identified and quantified with a targeted tandem mass spectrometry method using a QTRAP 5500 system (AB Sciex). Results: Our method has a limit of detection (LOD) in extracted water samples of <2 ng/mL for both glyphosate and AMPA. In complex intestinal medium, the LOD is 2 and 5 ng/mL for glyphosate and AMPA, respectively. These LODs allow for measurement at exposure-relevant concentrations. Glyphosate levels in a bioreactor model of porcine colon were determined and consequently it was verified whether AMPA was produced by porcine gut microbiota. Conclusions: The method presented here allows quantitation of glyphosate and AMPA in complex bioreactor fluids and thus enables studies of the impact of glyphosate and its metabolism on intestinal microbiota. In addition, the extraction protocol is compatible with an untargeted metabolomics analysis, thus allowing one to look for other perturbations caused by glyphosate in the same sample

The glyphosate formulation Roundup® LB plus influences the global metabolome of pig gut microbiota in vitro

Glyphosate is the world's most widely used herbicide, and its potential side effects on the intestinal microbiota of various animals, from honeybees to livestock and humans, are currently under discussion. Pigs are among the most abundant livestock animals worldwide and an impact of glyphosate on their intestinal microbiota function can have serious consequences on their health, not to mention the economic effects. Recent studies that addressed microbiota-disrupting effects focused on microbial taxonomy but lacked functional information. Therefore, we chose an experimental design with a short incubation time in which effects on the community structure are not expected, but functional effects can be detected. We cultivated intestinal microbiota derived from pig colon in chemostats and investigated the acute effect of 228 mg/d glyphosate acid equivalents from Roundup® LB plus, a frequently applied glyphosate formulation. The applied glyphosate concentration resembles a worst-case scenario for an 8–9 week-old pig and relates to the maximum residue levels of glyphosate on animal fodder. The effects were determined on the functional level by metaproteomics, targeted and untargeted meta-metabolomics, while variations in community structure were analyzed by 16S rRNA gene profiling and on the single cell level by microbiota flow cytometry. Roundup® LB plus did not affect the community taxonomy or the enzymatic repertoire of the cultivated microbiota in general or on the expression of the glyphosate target enzyme 5-enolpyruvylshikimate-3-phosphate synthase in detail. On the functional level, targeted metabolite analysis of short chain fatty acids (SCFAs), free amino acids and bile acids did not reveal significant changes, whereas untargeted meta-metabolomics did identify some effects on the functional level. This multi-omics approach provides evidence for subtle metabolic effects of Roundup® LB plus under the conditions applied

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies

Erneuerbare Energien in der Raumplanung. Ein Hindernislauf mit Tücken.

Die Energiewende stellt die Raumplanung vor große Herausforderungen. Insbesondere die Plannung und der Bau von Anlagen zur Gewinnung erneuerbarer Energien sind immer wieder hoch umstritten und selten einfach umzusetzen. Der Sammenband präsentiert mehrere Seminararbeiten, die unterschiedliche Aspekte zum Thema erörtern und viele Beispiele aus der Praxis darstellen

Recommendation of Good Practice in the Food-Processing Industry for Preventing and Handling Food Loss and Waste

Food-processing companies are controlled by societal influences and economic interests, but their efforts with regard to reducing food loss and waste are very different. This qualitative study aims to identify basic recommendations of good practice for the food-processing industry in order to prevent and handle food loss and waste. For this purpose, a comprehensive literature review was conducted in the field of food waste prevention and data was collected from thirteen German companies. The findings summarize the recommendations of good practice, which cover the entire supply chain from supplier to consumer and beyond. The analysis showed that the participating companies are already partially aware of operational measures, even if they are applied or mentioned without a systematic approach. Furthermore, the analysis revealed that most activities relate to internal matters, like processing, employees and utilization. However, the responsibility of food-processing companies does not end with internal processes to reduce food waste. The results show that some companies are already aware of their responsibility to be involved along the entire supply chain. Finally, the results show that the needs of consumers and suppliers must also be considered in order to reduce food waste, in addition to direct reduction measures. This paper highlights nine important stages and 53 basic recommendations for companies to address food loss and waste in order to improve their practices