Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry's disease.

Introduction: Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry's disease and healthy controls. Methods: Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness. Results: It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, p = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, p = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical staining revealed an adventitial VEGFα signal in α-GAL-Tg/KO mice, whereas no VEGFα signal could be detected in WT mice aortas. No differences in aortic angiostatin expression between α-GAL-Tg/KO- and WT mice could be visualized. The serum levels of VEGFα were significantly upregulated in patients with Fabry's disease compared with that in healthy controls (708.5 ± 426.3 vs. 458.5 ± 181.5 pg/ml, p = 0.048) and positively associated with albuminuria (r = 0.82, p < 0.0001) and elevated NTproBNP (r = 0.87, p < 0.0001) and hsTNT values (r = 0.41, p = 0.048) in male patients with Fabry's disease. For angiostatin, no significant difference was found between patients with Fabry's disease and healthy controls (747.6 ± 390.3 vs. 858.8 ± 599.3 pg/ml). Discussion: In conclusion, an overexpression of VEGFα and downregulation of its counter player angiostatin in aortic tissue of α-GAL-Tg/KO mice support the hypothesis of an underlying vasculopathy in Fabry's disease. Elevated VEGFα serum levels were also observed in patients with Fabry's disease and were positively associated with elevated markers of organ manifestation in males. These findings suggest that angiogenetic markers, such as VEGFα, may be potentially useful biomarkers for the detection of endothelial dysfunction in classical Fabry's disease.

Education Team Time Out in Oncologic Visceral Surgery Optimizes Surgical Resident Training and Team Communication-Results of a Prospective Trial.

BACKGROUND: Surgical education is highly dependent on intraoperative communication. Trainers must know the trainee's training level to ensure high-quality surgical training. A systematic preoperative dialogue (Educational Team Time Out, ETO) was established to discuss the steps of each surgical procedure. METHODS: Over 6 months, ETO was performed within a time limit of 3 minutes. Digital surveys on the utility of ETO and its impact on performance were conducted immediately after surgery and at the end of the study period among the staff of the participating disciplines (trainer, trainee, surgical nursing staff, anaesthesiologists, and medical students). The number of surgical substeps performed was recorded and compared with the equivalent period one year earlier. RESULTS: ETO was performed in 64 of the 103 eligible operations (62%). Liver resection (n = 37) was the most frequent procedure, followed by left-sided colorectal surgery (n = 12), partial pancreaticoduodenectomy (n = 6), right-sided hemicolectomies (n = 5), and thyroidectomies (n = 4). Anaesthesiologists most frequently reported that ETO had a direct impact on their work during surgery (90.9%). The influence scores were 46.8% for trainees, 8.8% for trainers, 53.3% for surgical nursing staff and 66.6% for medical students. During the implementation of ETO, a trend towards more assisted substeps in oncologic visceral surgery was seen compared to the corresponding period one year earlier (51% vs.40%; p = 0.11). CONCLUSION: ETO leads to improved intraoperative communication and more performed substeps during complex procedures, which increases motivation and practical training. This concept can easily be implemented in all surgical specialties to improve surgical education.

Monolithic high contrast grating on GaSb/AlAsSb based epitaxial structures for mid-infrared wavelength applications.

We demonstrate monolithic high contrast gratings (MHCG) based on GaSb/AlAs0.08Sb0.92 epitaxial structures with sub-wavelength gratings enabling high reflection of unpolarized mid-infrared radiation at the wavelength range from 2.5 to 5 µm. We study the reflectivity wavelength dependence of MHCGs with ridge widths ranging from 220 to 984 nm and fixed 2.6 µm grating period and demonstrate that peak reflectivity of above 0.7 can be shifted from 3.0 to 4.3 µm for ridge widths from 220 to 984 nm, respectively. Maximum reflectivity of up to 0.9 at 4 µm can be achieved. The experiments are in good agreement with numerical simulations, confirming high process flexibility in terms of peak reflectivity and wavelength selection. MHCGs have hitherto been regarded as mirrors enabling high reflection of selected light polarization. With this work, we show that thoughtfully designed MHCG yields high reflectivity for both orthogonal polarizations simultaneously. Our experiment demonstrates that MHCGs are promising candidates to replace conventional mirrors like distributed Bragg reflectors to realize resonator based optical and optoelectronic devices such as resonant cavity enhanced light emitting diodes and resonant cavity enhanced photodetectors in the mid-infrared spectral region, for which epitaxial growth of distributed Bragg reflectors is challenging.

Assessment of a novel smartglass-based point-of-care fusion approach for mixed reality-assisted targeted prostate biopsy: A pilot proof-of-concept study.

Purpose: While several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate. Methods: For prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10). Results: SMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p < 0.05) higher for SMART TB (47%) than for systematic biopsy (19%). Likelihood for PCA according to each core of a PIRADS lesion (17%, PIRADS 3; 58%, PIRADS 4; 67%, PIRADS 5) demonstrated convenient accuracy. Feasibility scores for SMART TB were high for practicality (10), multitasking (10), execution speed (9), comfort (8), improvement of surgery (8) and image quality (8), medium for physical stress (6) and device handling (6) and low for device weight (5) and battery autonomy (4). Conclusion: SMART TB has the potential to increase accuracy for PCA detection and might enhance cognitive MRI-guided targeted prostate biopsy in the future.

[Testing of practical surgical teaching at a distance-Experiences with a hybrid OSCE in surgery]. / Prüfung praktisch-chirurgischer Lehre auf Distanz ­ Erfahrungen mit einem Hybrid-OSCE in der Chirurgie.

BACKGROUND: The COVID-19 pandemic has changed medical teaching worldwide. Digital teaching and examinations are successful for cognitive learning objectives, whereas practical skills had to be carried out predominantly in person under strict hygiene standards. AIM: This study presents the opportunities and challenges of using a presence objective structured clinical examination (OSCE) at a distance with digital support. METHOD: Following surgical practical teaching an OSCE was conducted in presence, where students demonstrated practical skills in one room while the examiners were connected via videoconference from another room. Students were surveyed about the OSCE and sustained learning via a standardized online questionnaire after completion of the surgical teaching. Additionally, examiners were surveyed on their experiences. RESULTS: In the online survey 40 students participated (25% of n = 157 students contacted) and 36 completed questionnaires were analyzed. Overall, the implementation of an OSCE even under pandemic conditions was perceived as very positive by the students (92% of students n = 33). In particular, the acquisition of practical skills was rated as very high. For 78% (n = 28) of the students, the acquisition of competencies through the practical examination was particularly sustainable. The vast majority of students and examiners felt safe regarding infection control because of the hygiene concept (92%, n = 33). Overall, 80 students achieved grade 1 (51%), 71 students grade 2 (45.2%) and 6 students grade 3 (3.8%) (grade 1 = very good, grade 6 = very bad). CONCLUSION: Practical examinations are essential for checking practical learning objectives and can be implemented at a distance with a well-developed hygiene concept and digital support.

First-in-human study demonstrating the safety and clinical efficacy of novel anti-IL-17A monoclonal antibody CJM112 in moderate to severe plaque psoriasis.

BACKGROUND AND OBJECTIVE: Anti-IL-17A IgG/κ monoclonal antibody CJM112 binds both IL-17A and IL-17AF. The purpose of this First-in-Human study was to assess CJM112 effects on safety and efficacy in patients with moderate to severe plaque psoriasis. METHODS: This study had two parts: single ascending doses of 5-450 mg subcutaneous (s.c.) CJM112 (SAD) and multi-dose parallel groups of CJM112 15 mg, 50 mg and 150 mg s.c. low frequency or high frequency (MD). SAD/MD were double-blind, randomized and placebo-controlled; MD also included a secukinumab 150 mg s.c. arm as an active comparator. Patients 18-65 years with moderate to severe psoriasis were included in this study. The efficacy outcome was the change in Psoriasis Area Severity Index (PASI) from baseline to Week 4 in the SAD part of the study, and from baseline to Week 12 in the MD part. RESULTS: 96 patients were enrolled in this study (SAD, n = 42; MD, n = 54). In SAD, CJM112 doses from 15 mg and above demonstrated higher PASI responses compared with placebo at Week 12. CJM112 450 mg did not add further efficacy, but efficacy duration was prolonged compared with CJM112 150 mg. CJM112 MD resulted in a dose-dependent decrease in PASI over time to Week 12. CJM112 150 mg high frequency did not exceed the effect of CJM112 150 mg low frequency and had similar efficacy to secukinumab 150 mg. The safety profile of CJM112 was as expected for an antibody targeting IL-17A/IL-17AF. CONCLUSIONS: CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL-17AF did not translate to increased clinical efficacy compared with secukinumab.

[Metabolic acidosis of surprising origin in a 61-year-old female patient]. / Metabolische Azidose mit überraschender Ursache bei einer 61-jährigen Patientin.

A 61-year-old female patient presented to the emergency room with nausea. Laboratory findings revealed metabolic acidosis, which had to be associated with a sodium-glucose co-transporter­2 (SGLT2) inhibitor. Due to increasing prescription rates of SGLT2 inhibitors for diabetes mellitus, congestive heart failure or chronic renal insufficiency, a growing numbers of cases of SGLT2 inhibitor-associated ketoacidosis should be expected. Calculating the anion gap can provide orientation in the case of acidosis of unknown origin. Presumably, a relevant proportion of such cases of ketoacidosis is currently being overlooked or its diagnosis delayed.

Cost-effectiveness of stress CTP versus CTA in detecting obstructive CAD or in-stent restenosis in stented patients.

OBJECTIVES: The aim of this retrospective study was to determine cost-effectiveness of stress myocardial CT perfusion (CTP), coronary CT angiography (CTA), and the combination of both in suspected obstructive coronary artery disease (CAD) or in-stent restenosis (ISR) in patients with previous coronary stent implantation. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with CTA, CTP, and CTA + CTP. Model input parameters were obtained from published literature. Probabilistic sensitivity analysis was performed to evaluate overall model uncertainty. A single-variable deterministic sensitivity analysis evaluated the sensitivity of the results to plausible variations in model inputs. Cost-effectiveness was assessed based on a cost-effectiveness threshold of $100,000 per QALY. RESULTS: In the base-case scenario with willingness to pay of $100,000 per QALY, CTA resulted in total costs of $47,013.87 and an expected effectiveness of 6.84 QALYs, whereas CTP resulted in total costs of $46,758.83 with 6.93 QALYs. CTA + CTP reached costs of $47,455.63 with 6.85 QALYs. Therefore, strategies CTA and CTA + CTP were dominated by CTP in the base-case scenario. Deterministic sensitivity analysis demonstrated robustness of the model to variations of diagnostic efficacy parameters and costs in a broad range. CTP was cost-effective in the majority of iterations in the probabilistic sensitivity analysis as compared with CTA. CONCLUSIONS: CTP is cost-effective for the detection of obstructive CAD or ISR in patients with previous stenting and therefore should be considered a feasible approach in daily clinical practice. KEY POINTS: • CTP provides added diagnostic value in patients with previous coronary stents. • CTP is a cost-effective method for the detection of obstructive CAD or ISR in patients with previous stenting.

See (n)One, Do (n)One, Teach (n)One: Reality of Surgical Resident Training in Germany.

INTRODUCTION: Due to technological changes, working time restrictions and the creation of specialized centers, surgical training has changed. A competence-based learning technique of surgical skills is the sub-step practice approach, which has been proven important in nationwide opinion surveys. The aim of this prospective multi-center trial was to determine the status quo of the sub-step concept in Germany. METHODS: Over 6 months, the voluntarily participating centers evaluated the following index procedures: laparoscopic cholecystectomy (LCHE), laparoscopic and open sigmoid resection, minimally invasive inguinal hernia repair, thyroid resection and pylorus-preserving pancreaticoduodenectomy (PPPD). Patients with private insurance were excluded. The detailed sub-steps were documented as well as the reason why these were not performed. In addition, an online survey regarding the sub-step concept was performed before and after the study. RESULTS: In total, 21 centers included 2969 surgical procedures in 2018 for final analyses. While 24.4% of the procedures were performed by residents, sub-steps were performed in 22.2%. LCHE was most often performed completely by residents (43.3%), and PPPD revealed the highest rate of performed sub-steps (43.3%). Reasons for not assisting sub-steps to residents were often organizational and other reasons. After an initial increase, the number of performed sub-steps decreased significantly during the second half of the survey. The opinion survey revealed a high importance of the sub-step concept. The number of resident procedures was overestimated, and the number of performed sub-steps was underestimated. After the study, these estimations were more realistic. CONCLUSION: Even though the sub-step practice concept is considered highly important for surgical education, it needs to be put into practice more consequently. The current data suggest a low participation of surgical residents in the operating room, although the participating hospitals are most likely highly interested in surgical education, hence their voluntary participation. Conceptual changes and a control of surgical education are needed.

Magnetic Resonance Imaging Characteristics of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare hereditary disease presenting with distinct imaging features in middle-aged adults. This article describes the typical imaging features focusing on the longitudinal course of RVCL-S lesions. METHODS: In this study six subjects (five male, five related) with RVCL-S were retrospectively included from two university hospitals. The median age of symptom onset was 40 ± 6 years. Magnetic resonance imaging (MRI) covering baseline and a median follow-up period of 33 months was reviewed in a structured way focusing on morphology, contrast enhancement and diffusion restriction of brain lesions. RESULTS: All patients showed patchy, T2 hyperintense white matter lesions (mean number 7.7 ± 1.8) with a periventricular predominance at the frontal lobes (59%). In all subjects, rim-enhancing white matter lesions with temporary diffusion restriction were present for a mean of 5.0 ± 3.9 months. Median duration of blood brain barrier disruption was 20 months. CONCLUSION: Periventricular patchy white matter lesions in the frontal lobes as well as rim-enhancing lesions with prolonged diffusion restriction and long-lasting contrast enhancement are characteristic imaging findings in RCVL-S and can be helpful in the differential diagnosis.

["Dr. Google"-information-seeking behavior and disease-specific anxiety among men with localized prostate cancer]. / "Dr. Google" ­ Informationssuche und Krankheitsangst bei Männern mit lokal begrenztem Prostatakarzinom.

BACKGROUND AND OBJECTIVE: After the diagnosis of localized prostate cancer (LPCa), many men seek additional information about their disease. However, it is not yet proven how different sources of information influence uncertainty and disease-specific anxiety. The aim of this study is to investigate to what extent different types of information sources, the number of used sources and the perceived level of information are predictive of disease-specific anxiety. MATERIALS AND METHODS: Men with LPCa (N = 292; n = 150 radical prostatectomy, n = 142 active surveillance) completed questionnaires assessing sociodemographic variables, number and type of sources of information used, perceived level of information, and disease-specific anxiety. The association of information-seeking behavior with anxiety was tested using moderated sequential multiple regression. RESULTS: Men were 70 ± 7.2 years old and the survey was taken 47.9 ± 15.4 months after decision for therapy. The multiple regression analysis showed that, after controlling for potential covariates, internet usage (ß = 3.28; p > 0.001), number of sources (ß = 1.09; p > 0.01) and a lower level of informedness (ß = 4.49; p > 0.001) independently predicted variability of anxiety. In addition, the 3­way interaction (ß = 2.03; p > 0.05) accounted for a significant proportion of variance. Overall, the model explained 30% of the criterion variance. CONCLUSIONS: Our results show that many men with LPCa already use the internet as a source of information and that this online search is associated with increased disease-specific anxiety. It may be possible to reduce disease-specific anxiety and uncertainty if physicians advise their patients on the selection of reliable online sources.

Ultrafast Relaxation Dynamics of the Antiferrodistortive Phase in Ca Doped SrTiO_{3}.

The ultrafast dynamics of the octahedral rotation in Ca:SrTiO_{3} is studied by time-resolved x-ray diffraction after photoexcitation over the band gap. By monitoring the diffraction intensity of a superlattice reflection that is directly related to the structural order parameter of the soft-mode driven antiferrodistortive phase in Ca:SrTiO_{3}, we observe an ultrafast relaxation on a 0.2 ps timescale of the rotation of the oxygen octahedron, which is found to be independent of the initial temperature despite large changes in the corresponding soft-mode frequency. A further, much smaller reduction on a slower picosecond timescale is attributed to thermal effects. Time-dependent density-functional-theory calculations show that the fast response can be ascribed to an ultrafast displacive modification of the soft-mode potential towards the normal state induced by holes created in the oxygen 2p states.

Structured assessment of laparoscopic camera navigation skills: the SALAS score.

BACKGROUND: Tools are needed to assess laparoscopic camera navigation (LCN) in the operating room. Here, we aimed to develop an objective rating scale for LCN. STUDY DESIGN: We defined the following key aspects of LCN: operational field centering, correct angle of the horizon, correct instrument visualization, verbal commands from the operating surgeon, and manual corrections from the operating surgeon. We then developed a score based on intraoperative error evaluation from intraoperative recordings of 80 procedures. Finally, the newly developed score was validated by four different raters using video-based analysis of 20 elective laparoscopic cholecystectomies. RESULTS: We developed and validated a tool for the structured assessment of laparoscopic assistant skills (SALAS). This score showed good internal consistency, with a Cronbach's alpha of > 0.7. Intraclass correlation revealed a low interrater variability (ICC 0.866) for the total score. Comparison of experienced and inexperienced camera assistants revealed significantly better SALAS scores for experienced assistants (p < 0.05). CONCLUSION: Our present results show that SALAS score is valid, reliable, and practicable. This score can be used for future investigations of camera navigation efficiency and training.

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.

Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement.

The WD40-domain containing protein CORO2B is specifically enriched in glomerular podocytes and regulates the ventral actin cytoskeleton.

Podocytes are highly specialized epithelial cells essentially required to establish and maintain the kidney filtration barrier. Due to their complex cellular architecture these cells rely on an elaborated cytoskeletal apparatus providing plasticity as well as adaptive adhesion properties to withstand significant physical filtration forces. However, our knowledge about podocyte specific components of the cytoskeletal machinery is still incomplete. Employing cross-analysis of various quantitative omics-data sets we identify the WD40-domain containing protein CORO2B as a podocyte enriched protein. Furthermore, we demonstrate the distinct localization pattern of CORO2B to the ventral actin cytoskeleton serving as a physical linkage module to cell-matrix adhesion sites. Analysis of a novel Coro2b knockout mouse revealed that CORO2B modulates stress response of podocytes in an experimental nephropathy model. Using quantitative focal adhesome proteomics we identify the recruitment of CFL1 via CORO2B to focal adhesions as an underlying mechanism. Thus, we describe CORO2B as a novel podocyte enriched protein influencing cytoskeletal plasticity and stress adaptation.

Ultrafast Formation of a Charge Density Wave State in 1T-TaS_{2}: Observation at Nanometer Scales Using Time-Resolved X-Ray Diffraction.

Femtosecond time-resolved x-ray diffraction is used to study a photoinduced phase transition between two charge density wave (CDW) states in 1T-TaS_{2}, namely the nearly commensurate (NC) and the incommensurate (I) CDW states. Structural modulations associated with the NC-CDW order are found to disappear within 400 fs. The photoinduced I-CDW phase then develops through a nucleation and growth process which ends 100 ps after laser excitation. We demonstrate that the newly formed I-CDW phase is fragmented into several nanometric domains that are growing through a coarsening process. The coarsening dynamics is found to follow the universal Lifshitz-Allen-Cahn growth law, which describes the ordering kinetics in systems exhibiting a nonconservative order parameter.

["I will do laparoscopy somewhere else" : Total, highly immersive virtual reality without side effects?] / "Ich laparoskopier' dann woanders weiter" : Totale, hochimmersive virtuelle Realität ohne Nebenwirkungen?

BACKGROUND: For virtual reality laparosopic simulation we developed a new, highly immersive simulation mode. The goal of the current pilot study was to investigate if kinetosis or other negative vegetative side effects can be caused by a total virtual training set-up (TVRL). METHODS: In this study 20 participants with varying degrees of expertise in laparoscopy performed 3 tasks (i.e. ring exchange, fine dissection and cholecystectomy) in regular (VRL) and immersive mode (TVRL) with a head-mounted display (HMD) on a laparoscopic simulator. Aside from performance scores, the heart rate was recorded and the occurrence of vertigo was investigated. RESULTS: Surgical performance was independent of the VR mode (VRL or TVRL). Participants' heart rate was higher in TVRL without reaching statistical significance. Kinetosis occurred in two participants (10%) with a history of motion sickness. CONCLUSION: Laparoscopic training can take place in a total virtual environment with limited nagative vegetative side effects. Special attention should be paid to participants with a history of motion sickness. The development of TVRL enables new perspectives for surgical training.

Risk of Thrombus Fragmentation during Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: Periprocedural thrombus fragmentation is a relevant risk in endovascular stroke treatment. Because factors influencing its occurrence are largely unknown, this study addresses a potential relationship between thrombus histology and clot stability. MATERIALS AND METHODS: Eighty-five patients with anterior circulation stroke treated with thrombectomy were included in this retrospective study. The number and location of emboli after retrieving the primary thrombus, the number of maneuvers, and TICI scores were evaluated. H&E and neutrophil elastase staining of retrieved clots was performed, and semiquantitative measurements of thrombus components were correlated with procedural parameters. RESULTS: An inverse correlation between maneuvers required for thrombus retrieval and the number of distal and intermediate emboli was observed (Spearman r, -0.23; P = .032). Younger patients were at higher risk for periprocedural thrombus fragmentation (Spearman r, -0.23; P = .032). Bridging thrombolysis tended to be associated with fewer maneuvers (2 vs 3, P = .054) but more emboli (1 vs 0, P = .067). While no consistent correlation between procedural parameters and red/white blood cells and fibrin-/platelet fractions could be found, higher amounts of neutrophil elastase-positive cells within the thrombus were independently associated with the occurrence of multiple emboli (adjusted OR, 4.6; 95% CI, 1.1-19.7; P = .041) and lower rates of complete recanalization (adjusted OR, 0.3; 95% CI, 0.1-0.9; P = .050). CONCLUSIONS: Younger age, easy-to-retrieve thrombi, and bridging thrombolysis may be risk factors for periprocedural thrombus fragmentation. Findings from standard histologic stains did not provide insight into thrombectomy-relevant thrombus stability. However, higher neutrophil levels in the thrombus tissue were related to an increased risk of periprocedural thrombus fragmentation. This observation aligns with the proposed thrombolytic capacity of neutrophil elastase and points to its potential clinical relevance in the context of stroke thrombectomy.