Augmented 360° Three-Dimensional Virtual Reality for Enhanced Student Training and Education in Neurosurgery.

OBJECTIVE: This prospective study assesses the acceptance and usefulness of augmented 360° virtual reality (VR) videos for early student education and preparation in the field of neurosurgery. METHODS: Thirty-five third-year medical students participated. Augmented 360° VR videos depicting three neurosurgical procedures (lumbar discectomy, brain metastasis resection, clipping of an aneurysm) were presented during elective seminars. Multiple questionnaires were employed to evaluate conceptual and technical aspects of the videos. The analysis utilized ordinal logistic regression to identify crucial factors contributing to the learning experience of the videos. RESULTS: The videos were consistently rated as good to very good in quality, providing detailed demonstrations of intraoperative anatomy and surgical workflow. Students found the videos highly useful for their learning and preparation for surgical placements, and they strongly supported the establishment of a VR lounge for additional self-directed learning. Notably, 81% reported an increased interest in neurosurgery, and 47% acknowledged the potential influence of the videos on their future choice of specialization. Factors associated with a positive impact on students' interest and learning experience included high technical quality and comprehensive explanations of the surgical steps. CONCLUSIONS: This study demonstrated the high acceptance of augmented 360° VR videos as a valuable tool for early student education in neurosurgery. While hands-on training remains indispensable, these videos promote conceptual knowledge, ignite interest in neurosurgery, and provide a much-needed orientation within the operating room. The incorporation of detailed explanations throughout the surgeries with augmentation using superimposed elements, offers distinct advantages over simply observing live surgeries.

Comparison of intraoperative CT- and cone beam CT-based spinal navigation for the treatment of atlantoaxial instability.

BACKGROUND CONTEXT: Due to the complexity of neurovascular structures in the atlantoaxial region, spinal navigation for posterior C1-C2 instrumentation is nowadays a helpful tool to increase accuracy of surgery and safety of patients. Many available intraoperative navigation devices have proven their reliability in this part of the spine. Two main imaging techniques are used: intraoperative CT (iCT) and cone beam computed tomography (CBCT). PURPOSE: Comparison of iCT- and CBCT-based technologies for navigated posterior instrumentation in C1-C2 instability. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 81 consecutive patients from July 2014 to April 2020. OUTCOME MEASURES: Screw accuracy and operating time. METHODS: Patients with C1-C2 instability received posterior instrumentation using C2 pedicle screws, C1 lateral mass or pedicle screws. All screws were inserted using intraoperative imaging either using iCT or CBCT systems and spinal navigation with autoregistration technology. Following navigated screw insertion, a second intraoperative scan was performed to assess the accuracy of screw placement. Accuracy was defined as the percentage of correctly placed screws or with minor cortical breach (<2 mm) as graded by an independent observer compared to misplaced screws. RESULTS: A total of 81 patients with C1-C2 instability were retrospectively analyzed. Of these, 34 patients were operated with the use of iCT and 47 with CBCT. No significant demographic difference was found between groups. In the iCT group, 97.7% of the C1-C2 screws were correctly inserted; 2.3% showed a minor cortical breach (<2 mm); no misplacement (>2 mm). In the CBCT group, 98.9% of screws were correctly inserted; no minor pedicle breach; 1.1% showed misplacement >2 mm. Accuracy of screw placement demonstrated no significant difference between groups. Both technologies allowed sufficient identification of screw misplacement intraoperatively leading to two screw revisions in the iCT and three in the CBCT group. Median time of surgery was significantly shorter using CBCT technology (166.5 minutes [iCT] vs 122 minutes [CBCT]; p<.01). CONCLUSIONS: Spinal navigation using either iCT- or CBCT-based systems with autoregistration allows safe and reliable screw placement and intraoperative assessment of screw positioning. Using the herein presented procedural protocols, CBCT systems allow shorter operating time.

The Use of Intraoperative CT Hounsfield Unit Values for the Assessment of Bone Quality in Patients Undergoing Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To evaluate the accuracy of intraoperatively measured computed tomography (CT) Hounsfield unit (HU) values by comparison with preoperative CT HU values and to compare the radiation exposure between preoperative and intraoperative CT scans. METHODS: HU values of lumbar vertebrae were measured and compared between preoperative and intraoperative CT scans in patients undergoing lumbar interbody fusion. In patient group one, Canon CT scanners were used preoperatively and the AIRO CT scanner was used intraoperatively. In patient group two, Canon CT scanners were used preoperatively and the O-arm Cone Beam CT (CBCT) scanner was used intraoperatively. In a subgroup analysis of patient group one, radiation by means of CT Dose Index (CTDI) was compared between Canon and AIRO CT scanners. RESULTS: In the first patient group, a total of 250 vertebrae were analysed in 74 patients showing a strong Pearson correlation of >.94 between pre- and intraoperative HU values. Bland-Altman analysis indicated consistency and equivalence with a bias of 3.9 and 95% limits of agreement from -27.17 to 34.97 when comparing all pre- and intraoperative HU values of L1-5. In the second patient group, a total of 27 vertebrae were analysed in 10 patients showing weak Pearson correlation and Bland-Altman analysis indicated no equivalence. CTDI did not differ between Canon and AIRO CT scanners. CONCLUSION: Correct and reliable CT HU measurement as mandatory key factor for the intraoperative assessment of bone quality and robotic-assisted surgery is feasible with intraoperative AIRO CT imaging without increase of radiation exposure.

The gut hormone glucose-dependent insulinotropic polypeptide is downregulated in response to myocardial injury.

BACKGROUND: The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its metabolic function GIP has been found to exhibit direct cardio- and atheroprotective effects in mice and to be associated with cardiovascular prognosis in patients with myocardial infarction. The aim of this study was to characterize endogenous GIP levels in patients with acute myocardial infarction. METHODS AND RESULTS: Serum concentrations of GIP were assessed in 731 patients who presented with clinical indication of coronary angiography. Circulating GIP levels were significantly lower in patients with STEMI (ST-elevation myocardial infarction; n=100) compared to clinically stable patients without myocardial infarction (n=631) (216.82 pg/mL [Q1-Q3: 52.37-443.07] vs. 271.54 pg/mL [Q1-Q3: 70.12-542.41], p = 0.0266). To characterize endogenous GIP levels in patients with acute myocardial injury we enrolled 18 patients scheduled for cardiac surgery with cardiopulmonary bypass and requirement of extracorporeal circulation as a reproducible condition of myocardial injury. Blood samples were drawn directly before surgery (baseline), upon arrival at the intensive care unit (ICU), 6 h post arrival to the ICU and at the morning of the first and second postoperative days. Mean circulating GIP concentrations decreased in response to surgery from 45.3 ± 22.6 pg/mL at baseline to a minimum of 31.9 ± 19.8 pg/mL at the first postoperative day (p = 0.0384) and rose again at the second postoperative day (52.1 ± 28.0 pg/mL). CONCLUSIONS: Circulating GIP levels are downregulated in patients with myocardial infarction and following cardiac surgery. These results might suggest nutrition-independent regulation of GIP secretion following myocardial injury in humans.

Motor excitability in bilateral moyamoya vasculopathy and the impact of revascularization.

OBJECTIVE: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.

Oblique insertion of a straight cage during single level TLIF procedure proves to be non-inferior in terms of restoring segmental lordosis.

Introduction: With increasing relevance of the postoperative spinopelvic alignment, achieving optimal restoration of segmental lordosis (SL) during transforaminal lumbar interbody fusion (TLIF) has become increasingly important. However, despite the easier insertion of the straight cage, its potential to restore SL is still considered inferior to the preferred insert-and-rotate technique with a banana-shaped cage. Research question: To determine, if simple oblique insertion of a straight cage allows for an equally effective restoration of SL, but reduces risk for intraoperative cage subsidence requiring revision surgery. Material and methods: The authors retrospectively identified 81 patients who underwent single-level TLIF between 11/2017-03/2020. 40 patients were included in the straight cage group, 41 patients in the banana cage group. The authors determined pre- and postoperative SL from plain lateral radiographs. Bone density was analyzed on computed tomographs using Hounsfield unit (HU) values. Results: Both cage types were equally effective in restoring SL. However, 7.3% in the banana cage group, but none in the straight cage group, had to undergo revision surgery due to intraoperative cage subsidence. This was related to reduced bone density with lower HU values. Discussion: With an extended dorsal release, the straight cage may be equally effective in restoring SL. Since no repositioning is needed after oblique insertion, the straight cage might cause less intraoperative endplate violation. Conclusion: Provided an adequate surgical technique, both cage types might be equally effective in restoring SL after one-level TLIF surgery. However, the straight cage might represent the safer alternative in patients with reduced bone quality.

Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction.

AIMS: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1. Relevance of PYY in the context of cardiovascular disease has not been explored. In this study, we aimed to investigate PYY serum concentrations in patients with acute myocardial infarction and to evaluate their association with cardiovascular events. MATERIAL AND METHODS: PYY levels were assessed in 834 patients presenting with acute myocardial infarction (553 Non-ST-Elevation Myocardial Infarction (NSTEMI) and 281 ST-Elevation Myocardial Infarction (STEMI)) at the time of hospital admission. The composite outcomes of first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke (3-P-MACE), and all-cause mortality were assessed with a median follow-up of 338 days. RESULTS: PYY levels were significantly associated with age and cardiovascular risk factors, including hypertension, diabetes, and kidney function in addition to biomarkers of heart failure (NT-pro BNP) and inflammation (hs-CRP). Further, PYY was significantly associated with 3-P-MACE (HR: 1.7; 95% CI: 1-2.97; p = 0.0495) and all-cause mortality (HR: 2.69; 95% CI: 1.61-4.47; p = 0.0001) by univariable Cox regression analyses, which was however lost after adjusting for multiple confounders. CONCLUSIONS: PYY levels are associated with parameters of cardiovascular risk as well as cardiovascular events and mortality in patients presenting with acute myocardial infarction. However, this significant association is lost after adjustment for further confounders.

Glucagon-like peptide 1 levels predict cardiovascular risk in patients with acute myocardial infarction.

AIMS: Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone inducing post-prandial insulin secretion. Glucagon-like peptide 1 levels were recently found to be increased in patients with acute myocardial infarction. Glucagon-like peptide 1 receptor agonists improve cardiovascular outcomes in patients with diabetes. The aim of this study was to assess the predictive capacity of GLP-1 serum levels for cardiovascular outcome in patients with myocardial infarction. METHODS AND RESULTS: In 918 patients presenting with myocardial infarction [321 ST-segment elevation myocardial infarction and 597 non-ST-segment elevation myocardial infarction (NSTEMI)] total GLP-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of hospital admission. The primary composite outcome of the study was the first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Kaplan-Meier survival plots and univariable Cox regression analyses found GLP-1 to be associated with adverse outcome [hazard ratio (HR) of logarithmized GLP-1 values: 6.29, 95% confidence interval (CI): 2.67-14.81; P < 0.0001]. After further adjustment for age, sex, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterinaemia, glomerular filtration rate (GFR) CKD-EPI, hs-CRP, hs-Troponin T, and NT-proBNP levels the HR remained significant at 10.98 (95% CI: 2.63-45.90; P = 0.0010). Time-dependent receiver operating characteristic curve analyses illustrated that GLP-1 levels are a strong indicator for early events. For events up to 30 days after admission, GLP-1 proved to be superior to other biomarkers including hs-Troponin T, GFR CKD-EPI, hs-CRP, and NT-proBNP. Adjustment of the GRACE risk estimate by addition of GLP-1 increased the area under the receiver operating characteristic curve over time in NSTEMI patients. CONCLUSION: In patients hospitalized for myocardial infarction, GLP-1 levels are associated with cardiovascular events.

Epitope specificity of anti-synapsin autoantibodies: Differential targeting of synapsin I domains.

OBJECTIVE: To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin. METHODS: Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls. RESULTS: IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF. CONCLUSIONS: Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I.

The incretin hormone GIP is upregulated in patients with atherosclerosis and stabilizes plaques in ApoE-/- mice by blocking monocyte/macrophage activation.

OBJECTIVE: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists. However, little is known on the role of the other main incretin in the cardiovascular system. The aim of this study was to characterize GIP in atherosclerotic cardiovascular disease. METHODS AND RESULTS: Serum concentrations of GIP were assessed in 731 patients who presented for elective coronary angiography at the University Hospital Aachen. While GIP concentrations were not associated with coronary artery disease (CAD), we found 97 patients with PAD (peripheral artery disease) vs. 634 without PAD to have higher circulating GIP levels (413.0 ± 315.3 vs. 332.7 ± 292.5 pg/mL, p = 0.0165). GIP levels were independently related to PAD after multivariable adjustment for CAD, age, sex, BMI, hypertension, diabetes, CRP, WBC, and smoking. To investigate the functional relevance of elevated GIP levels in human atherosclerotic disease, we overexpressed GIP (1-42) in ApoE-/- mice fed a Western diet for 12 weeks using an adeno-associated viral vector system. GIP overexpression led to reduced atherosclerotic plaque macrophage infiltration and increased collagen content compared to control (LacZ) with no change in overall lesion size, suggesting improved plaque stability. Mechanistically, we found GIP treatment to reduce MCP-1-induced monocyte migration under In vitro conditions. Additionally, GIP prevented proinflammatory macrophage activation leading to reduced LPS-induced IL-6 secretion and inhibition of MMP-9 activity, which was attributable to GIP dependent inhibition of NfκB, JNK-, ERK, and p38 in endotoxin activated macrophages. CONCLUSION: Elevated concentrations of the incretin hormone GIP are found in patients with atherosclerotic cardiovascular disease, while GIP treatment attenuates atherosclerotic plaque inflammation in mice and abrogates inflammatory macrophage activation in vitro. These observations identified GIP as a counterregulatory vasoprotective peptide, which might open new therapeutic avenues for the treatment of patients with high cardiovascular risk.

Synapsin-antibodies in psychiatric and neurological disorders: Prevalence and clinical findings.

OBJECTIVE: To study the prevalence of autoantibodies to synapsin in patients with psychiatric and neurological disorders and to describe clinical findings in synapsin antibody positive patients. METHODS: Sera of 375 patients with different psychiatric and neurological disorders and sera of 97 healthy controls were screened (dilution 1:320) for anti-synapsin IgG using HEK293 cells transfected with rat synapsin Ia. Positive sera were further analyzed by immunoblots with brain tissue from wild type and synapsin knock out mice and with HEK293 cells transfected with human synapsin Ia and Ib. Binding of synapsin IgG positive sera to primary neurons was studied using murine hippocampal neurons. RESULTS: IgG in serum from 23 (6.1%) of 375 patients, but from none of the 97 healthy controls (p=0.007), bound to rat synapsin Ia transfected cells with a median (range) titer of 1:1000 (1:320-1:100,000). Twelve of the 23 positive sera reacted with a protein of the molecular size of synapsin I in immunoblots of wild type but not of synapsin knock out mouse brain tissue. Out of 19/23 positive sera available for testing, 13 bound to human synapsin Ia and 16 to human synapsin Ib transfected cells. Synapsin IgG positive sera stained fixed and permeabilized murine hippocampal neurons. Synapsin IgG positive patients had various psychiatric and neurological disorders. Tumors were documented in 2 patients (melanoma, small cell lung carcinoma); concomitant anti-neuronal or other autoantibodies were present in 8 patients. CONCLUSIONS: Autoantibodies to human synapsin Ia and Ib are detectable in a proportion of sera from patients with different psychiatric and neurological disorders, warranting further investigation into the potential pathophysiological relevance of these antibodies.

Disordered nanostructures by hole-mask colloidal lithography for advanced light trapping in silicon solar cells.

We report on the fabrication of disordered nanostructures by combining colloidal lithography and silicon etching. We show good control of the short-range ordered colloidal pattern for a wide range of bead sizes from 170 to 850 nm. The inter-particle spacing follows a Gaussian distribution with the average distance between two neighboring beads (center to center) being approximately twice their diameter, thus enabling the nanopatterning with dimensions relevant to the light wavelength scale. The disordered nanostructures result in a lower integrated reflectance (8.1%) than state-of-the-art random pyramid texturing (11.7%) when fabricated on 700 µm thick wafers. When integrated in a 1.1 µm thin crystalline silicon slab, the absorption is enhanced from 24.0% up to 64.3%. The broadening of resonant modes present for the disordered nanopattern offers a more broadband light confinement compared to a periodic nanopattern. Owing to its simplicity, versatility and the degrees of freedom it offers, this potentially low-cost bottom-up nanopatterning process opens perspectives towards the integration of advanced light-trapping schemes in thin solar cells.