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PURPOSE: Minimally invasive cochlear implant surgery using a micro-stereotactic surgical targeting system with on-site moulding of the template aims for a reliable, less experience-dependent access to the inner ear under maximal reduction of trauma to anatomic structures. We present an accuracy evaluation of our system in ex-vivo testing. METHODS: Eleven drilling experiments were performed on four cadaveric temporal bone specimens. The process involved preoperative imaging after affixing the reference frame to the skull, planning of a safe trajectory preserving relevant anatomical structures, customization of the surgical template, execution of the guided drilling and postoperative imaging for determination of the drilling accuracy. Deviation between the drilled and desired trajectories was measured at different depths. RESULTS: All drilling experiments were successfully performed. Other than purposely sacrificing the chorda tympani in one experiment, no other relevant anatomy, such as facial nerve, chorda tympani, ossicles or external auditory canal were harmed. Deviation between the desired and achieved path was found to be 0.25 ± 0.16 mm at skulls' surface and 0.51 ± 0.35 mm at the target level. The closest distance of the drilled trajectories' outer circumference to the facial nerve was 0.44 mm. CONCLUSIONS: We demonstrated the usability for drilling to the middle ear on human cadaveric specimen in a pre-clinical setting. Accuracy proved to be suitable for many applications such as procedures within the field of image-guided neurosurgery. Promising approaches to reach sufficient submillimetre accuracy for CI surgery have been outlined.
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Implante Coclear , Implantes Cocleares , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , Implante Coclear/métodos , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , CadáverRESUMO
OBJECTIVES: (1) To evaluate the feasibility of a non-invasive, novel, simple insertion tool to perform automated, slow insertions of cochlear implant electrode arrays (EA) into a human cadaver cochlea; (2) to estimate the handling time required by our tool. METHODS: Basic science study conducted in an experimental OR. Two previously anonymized human cadaver heads, three commercially available EAs, and our novel insertion tool were used for the experiments. Our tool operates as a hydraulic actuator that delivers an EA at continuous velocities slower than manually feasible. INTERVENTION(S): the human cadaver heads were prepared with a round-window approach for CI surgery in a standard fashion. Twelve EA insertion trials using our tool involved: non-invasive fixation of the tool to the head; directing the tool to the round window and EA mounting onto the tool; automated EA insertion at approximately 0.1 mm/s driven by hydraulic actuation. Outcome measurement(s): handling time of the tool; post-insertion cone-beam CT scans to provide intracochlear evaluation of the EA insertions. RESULTS: Our insertion tool successfully inserted an EA into the human cadaver cochlea (n = 12) while being attached to the human cadaver head in a non-invasive fashion. Median time to set up the tool was 8.8 (7.2-9.4) min. CONCLUSION: The first insertions into the human cochlea using our novel, simple insertion tool were successful without the need for invasive fixation. The tool requires < 10 min to set up, which is clinically acceptable. Future assessment of intracochlear trauma is needed to support its safety profile for clinical translation.
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Implante Coclear , Implantes Cocleares , Cadáver , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Eletrodos Implantados , Humanos , Janela da Cóclea/cirurgiaRESUMO
Undecylenic acid, a monounsaturated fatty acid, is currently in clinical use as a topical antifungal agent, however the potential for therapeutic application in other disease settings has not been investigated. In this study, we describe a novel platform for the solubilization of fatty acids using amino acids and utilize this approach to define a tumoricidal activity and underlying mechanism for undecylenic acid. We examined a novel formulation of undecylenic acid compounded with L-Arginine, called GS-1, that induced concentration-dependent tumor cell death, with undecylenic acid being the cytotoxic component. Further investigation revealed that GS-1-mediated cell death was caspase-dependent with a reduction in mitochondrial membrane potential, suggesting a pro-apoptotic mechanism of action. Additionally, GS-1 was found to localize intracellularly to lipid droplets. In contrast to previous studies where lipid droplets have been shown to be protective against fatty acid-induced cell death, we showed that lipid droplets could not protect against GS-1-induced cytotoxicity. We also found a role for Fatty Acid Transport Protein 2 (FATP2) in the uptake of this compound. Collectively, this study demonstrates that GS-1 has effective pro-apoptotic antitumor activity in vitro and, together with the novel platform of fatty acid solubilization, contributes to the re-emerging field of fatty acids as potential anti-cancer therapeutics.
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Apoptose , Ácidos Undecilênicos , Ácidos Undecilênicos/farmacologia , Ácidos Graxos/química , Caspases , Ácidos Graxos Monoinsaturados/farmacologiaRESUMO
OBJECTIVES: (1) To assess variations of the human intracochlear anatomy and quantify factors which might be relevant for cochlear implantation (CI) regarding surgical technique and electrode design. (2) Search for correlations of these factors with clinically assessable measurements. DESIGN: Human temporal bone study with micro computed tomography (µCT) data and analysis of intracochlear geometrical variations: µCT data of 15 fresh human temporal bones was generated, and the intracochlear lumina scala tympani (ST) and scala vestibuli were manually segmented using custom software specifically designed for accurate cochlear segmentation. The corresponding datasets were processed yielding 15 detailed, three-dimensional cochlear models which were investigated in terms of the scalae height, cross-sectional size, and rotation as well as the interrelation of these factors and correlations to others. RESULTS: The greatest anatomical variability was observed within the round window region of the cochlea (basal 45°), especially regarding the cross-sectional size of the ST and its orientation relative to the scala vestibuli, which were found to be correlated (p < 0.001). The cross-sectional height of the ST changes substantially for both increasing cochlear angles and lateral wall distances. Even small cochleae were found to contain enough space for all commercially available CI arrays. Significant correlations of individual intracochlear parameters to clinically assessable ones were found despite the small sample size. CONCLUSION: While there is generally enough space within the ST for CI, strong intracochlear anatomical variations could be observed highlighting the relevance of both soft surgical technique as well as a highly flexible and self-adapting cochlear implant electrode array design. Cochlear dimensions (especially at the round window) could potentially be used to indicate surgically challenging anatomies.
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Implante Coclear , Implantes Cocleares , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Estudos Transversais , Humanos , Rampa do Tímpano/diagnóstico por imagem , Osso Temporal/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
PURPOSE: Latest research on cochlear implantations focuses on hearing preservation during insertion of the implant's electrode array by reducing insertion trauma. One parameter which may influence trauma is insertion speed. The objective of this study was to extend the range of examined insertion speeds to include ultra-low velocities, being lower than manually feasible, and investigate whether these reduce insertion forces. METHODS: 24 custom-made cochlear implant test samples were fabricated and inserted into an artificial scala tympani model using 12 different insertion speeds while measuring the resulting insertion forces. Three commercially available slim straight electrode carriers were inserted using the same setup to analyze whether the results are comparable. RESULTS: Insertions of the test samples using high insertion speeds (2.0/2.8 mm/s) showed significantly higher insertion forces than insertions done with low insertion speeds (0.2 mm/s) or ultra-low insertion speeds (< 0.1 mm/s). The insertions with commercial slim straight electrode arrays showed significantly reduced insertion forces when using a low insertion speed as well. CONCLUSIONS: Slow insertions showed significantly reduced insertion forces. Insertion speeds which are lower than manually feasible showed even lower insertion forces.
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Implante Coclear/métodos , Implantes Cocleares , Humanos , Modelos AnatômicosRESUMO
PURPOSE: Patient specific selection of cochlear implants would benefit from pre-operative knowledge of cochlear length. Several methods for its measurement or estimation have been described in literature. This study focused on the achievable accuracy in clinically available imaging. METHODS: Five simplified cochlea models milled into porcine bone were scanned in water using clinical cone beam computed tomography. Due to their well-known dimensions these phantoms served as gold standard for the length measurements. Each phantom was measured ten times using the custom software Comet. In addition, cochleae in ten image datasets taken indiscriminately from clinical routine were measured ten times each to test the precision under realistic conditions. The results were also compared to estimations based on the diameter of the basal turn (A value) as described in literature. RESULTS: Measurement accuracy of the phantoms' lengths was high (average error: - 0.2 mm; standard deviation: 0.3 mm). The pooled standard deviation for the measurements in clinical datasets was 0.6 mm. Errors resulted mainly from problems locating the helicotrema. The estimations differed on average - 1.7 to + 0.4 mm from the manual measurements and had standard deviations between 0.5 and 0.6 mm depending on the algorithm. CONCLUSIONS: The program Comet was successfully used to accurately measure the length of the cochlea models in clinically available imaging. The lower image quality of patient scans reduced the precision of the measurement. Estimations using the A value are a quicker alternative for averagely sized cochleae in cases where the lack of accuracy is tolerable.
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Ducto Coclear/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Animais , Ducto Coclear/anatomia & histologia , Implante Coclear/instrumentação , Implantes Cocleares , Humanos , Modelos Anatômicos , Imagens de Fantasmas , Software , SuínosRESUMO
PRIMARY OBJECTIVE: The purpose of this study was to investigate the effects of mild traumatic brain injury (mTBI) on multiple postural indices that characterize body sway behaviour. METHODS AND PROCEDURES: The body's centre of pressure (COP) displacement was recorded from 11 individuals with a history of mTBI (29.4 ± 6.7 years old) and 11 healthy controls (26.8 ± 3.7 years old) performing bipedal stance on a force platform for 120 seconds. Spatio-temporal (area, amplitude and mean velocity of the COP displacement) and frequency characteristics (frequency containing 80% of the power spectral density) of the body oscillation, as well as its dynamic characteristics (sample entropy estimate of the COP displacement) were extracted from COP signals. MAIN OUTCOMES AND RESULTS: All postural indices studied were significantly affected by mTBI (p < 0.010). Participants with a history of mTBI presented a larger, slower, and more random body oscillation compared to controls. CONCLUSION: The results suggest that (a) balance deficits can be recognized as an effect of mTBI; (b) balance deficits induced by mTBI are multi-dimensional, affecting all three domains included in this study; and
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Concussão Encefálica/fisiopatologia , Equilíbrio Postural/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The aim of the study was to evaluate insertion forces during manual insertion of a straight atraumatic electrode in human temporal bones, and post-implantation histologic evaluation of the samples to determine whether violation of intracochlear structures is related to insertion forces. In order to minimize intracochlear trauma and preserve residual hearing during cochlear implantation, knowledge of the insertion forces is necessary. Ten fresh frozen human temporal bones were prepared with canal wall down mastoidectomy. All samples were mounted on a one-axis force sensor. Insertion of a 16-mm straight atraumatic electrode was performed from different angles to induce "traumatic" insertion. Histologic evaluation was performed in order to evaluate intracochlear trauma. In 4 of 10 samples, dislocation of the electrode into scala vestibuli was observed. The mean insertion force for all 10 procedures was 0.003 ± 0.005 N. Insertion forces measured around the site of dislocation to scala vestibuli in 3 of 4 samples were significantly higher than insertion forces at the same location of the cochleae measured in samples without trauma (p < 0.04). Mean force during the whole insertion process of the straight atraumatic electrode is lower than reported by other studies using longer electrodes. Based on our study, insertion forces leading to basilar membrane trauma may be lower than the previously reported direct rupture forces.
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Membrana Basilar , Implante Coclear , Implantes Cocleares/efeitos adversos , Complicações Intraoperatórias , Osso Temporal , Membrana Basilar/lesões , Membrana Basilar/patologia , Implante Coclear/efeitos adversos , Implante Coclear/métodos , Humanos , Complicações Intraoperatórias/patologia , Complicações Intraoperatórias/prevenção & controle , Modelos Anatômicos , Ruptura/etiologia , Ruptura/patologia , Ruptura/prevenção & controle , Osso Temporal/patologia , Osso Temporal/cirurgiaRESUMO
Within the field of hearing prosthetics it is known that patients with sufficient residual hearing benefit from the simultaneous employment of hearing aid and cochlear implant. Several attempts have been proposed to combine the sources of the corresponding acoustic and electric stimuli in a single, implantable device. However, since only little is known about the effect of also applying the acoustic stimulus locally from within the inner ear, the current state of research lacks detailed knowledge on the optimal stimulation at the corresponding bionic interface. Within this manuscript, a simple but yet physiologically-based inner ear model is presented which was designed specifically for the analysis of local acoustic or mechanical inner ear stimulation. A detailed model analysis is performed showing that it is capable of mirroring the known mechanical phenomena of this particular stimulation approach. Using the model, it is demonstrated how amplitude and phase shift values of stimuli applied from within the inner ear should be chosen for optimal inner ear stimulation.
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Cóclea/fisiologia , Fenômenos Mecânicos , Modelos Biológicos , Acústica , Fenômenos Biomecânicos , Próteses NeuraisRESUMO
The integration of a shape memory actuator is a potential mechanism to achieve a consistent perimodiolar position after electrode insertion during cochlear implant surgery. After warming up, and therefore activation of the shape memory effect, the electrode array will change from a straight configuration into a spiral shaped one leading to a final position close to the modiolus. The aim of this study was to investigate whether the integration of an additional thin wire (referred to as an "inlay") made of Nitinol, a well-established shape memory alloy, in a conventional hearing preservation electrode array will affect the insertion behaviour in terms of increased risk of insertion trauma. Six conventional Hybrid-L electrode arrays (Cochlear Ltd., Sydney, Australia) were modified to incorporate a wire inlay made of Nitinol. The diameter of the wires was 100 µm with a tapered tip region. Electrodes were inserted into human temporal bone specimens using a standard surgical approach. After insertion and embedding in epoxy resin, histological sections were prepared to evaluate insertion trauma. Insertion was straightforward and no difficulties were observed. The addition of a shape memory wire, thin but also strong enough to curl the electrode array, does not result in histologically detectable insertion trauma. Atraumatic insertion seems possible.
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Ligas , Implante Coclear/métodos , Implantes Cocleares , Osso Temporal/cirurgia , Cadáver , Implante Coclear/efeitos adversos , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Desenho de PróteseRESUMO
Phenoxybenzamine (PBZ) is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI). While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD). Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM-1 mM) and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1ß, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.
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Lesões Encefálicas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fenoxibenzamina/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Morte Celular , Sobrevivência Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Aprendizagem em Labirinto , Memória , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Fenoxibenzamina/administração & dosagem , Fenoxibenzamina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: During the insertion of cochlear implant (CI) electrode arrays, forces occur which may cause trauma and poorer hearing outcomes. Unfortunately, research groups investigating factors influencing insertion forces come to contradicting results, especially regarding insertion speed. This study was conducted to investigate the origin of these contradicting results and to determine how different testing conditions influence experimental findings. METHODS: Repeated, automated insertions with three different FLEX28 CI electrode arrays (MED-EL, Innsbruck, Austria) were performed into a newly developed, anatomically correct and 3D-printed mean scala tympani phantom. The testing protocol for each electrode included variations in insertion speed (v = 0.1-2.0 mm/s) and lubrication (90%, 50%, and 10% liquid soap), resulting in 51 insertions per electrode array and a total of 153 insertions. RESULTS: The test setup and protocol allowed for repeatable insertions with only minimal change in the morphology of the insertion force profiles per testing condition. Strong but varying dependencies of the maximal insertion forces and work were found regarding both lubrication and speed: work-speed dependency is constant for the 10% lubricant, negative for the 50% lubricant and positive for the 90% lubricant. CONCLUSION: Our results can explain part of the contradicting results found within previous studies by translating interrelations known from lubricated rubber friction to the field of CI electrode array insertion. We show that the main driver behind measured bulk forces are most likely the generated friction forces, which are strongly dependent on insertion speed and lubrication. The employed test setup allows for conducting repeatable and comparable insertion studies, which can be recapitulated by other centers due to the detailed explanation of the test setup as well as the developed and freely available insertion phantom. This study hence represents another important step toward standardizing CI array insertion testing.
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Implante Coclear , Implantes Cocleares , Lubrificação , Cóclea , LubrificantesRESUMO
BACKGROUND: Minimally invasive cochlear implant surgery by using a microstereotactic frame demands solid connection to the bone. We aimed to determine the stability of commercially available orthodontic miniscrews to evaluate their feasibility for frame's fixation. In addition, which substitute material most closely resembles the mechanical properties of the human temporal bone was evaluated. METHODS: Pull-out tests were carried out with five different types of orthodontic miniscrews in human temporal bone specimens. Furthermore, short fiber filled epoxy (SFFE), solid rigid polyurethane (SRPU50), bovine femur, and porcine iliac bone were evaluated as substitute materials. In total, 57 tests in human specimens and 180 tests in the substitute materials were performed. RESULTS: In human temporal bone, average pull-out forces ranged from 220 N to 285 N between screws. Joint stiffness in human temporal bone ranged between 14 N/mm and 358 N/mm. Statistically significant differences between the tested screws were measured in terms of stiffness and elastic energy. One screw type failed insertion due to tip breakage. No significant differences occurred between screws in maximum pull-out force. The average pull-out values of SFFE were 14.1 N higher compared to human specimen. CONCLUSION: Orthodontic miniscrews provided rigid fixation when partially inserted in human temporal bone, as evidenced by pull-out forces and joint stiffness. Average values exceeded requirements despite variations between screws. Differences in stiffness and elastic energy indicate screw-specific interface mechanics. With proper insertion, orthodontic miniscrews appear suitable for microstereotactic frame anchoring during minimally invasive cochlear implant surgery. However, testing under more complex loading is needed to better predict clinical performance. For further pull-out tests, the most suitable substitute material is SFFE.
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Parafusos Ósseos , Osso Temporal , Osso Temporal/cirurgia , Humanos , Animais , Suínos , Implante Coclear/métodos , Teste de Materiais , Cadáver , Bovinos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Objectives: Despite the success of cochlear implant (CI) surgery for hearing restoration, reducing CI electrode insertion forces is an ongoing challenge with the goal to further reduce post-implantation hearing loss. While research in this field shows that both friction and quasistatic pressure forces occur during CI insertion, there is a lack of studies distinguishing between these origins. The present study was conducted to analyze the contribution of both force phenomena during automated CI insertion. Methods: Five MED-EL FLEX28 CI electrode arrays were inserted into both a regular and uncoiled version of the same average scala tympani (ST). Both ST models had a pressure release hole at the apical end, which was kept open or closed to quantify pressure forces. ST models were filled with different sodium dodecyl sulfate (SDS) lubricants (1, 5, and 10% SDS, water). The viscosity of lubricants was determined using a rheometer. Insertions were conducted with velocities ranging from v= 0.125 mm/s to 2.0 mm/s. Results: Viscosity of SDS lubricants at 20°C was 1.28, 1.96, and 2.51 mPas for 1, 5, and 10% SDS, respectively, which lies within the values reported for human perilymph. In the uncoiled ST model, forces remained within the noise floor (maximum: 0.049 × 10-3 N ± 1.5 × 10-3 N), indicating minimal contribution from quasistatic pressure. Conversely, forces using the regular, coiled ST model were at least an order of magnitude larger (minimum: Fmax = 28.95 × 10-3 N, v = 1 mm/s, 10% SDS), confirming that friction forces are the main contributor to total insertion forces. An N-way ANOVA revealed that both lubricant viscosity and insertion speed significantly reduce insertion forces (p < 0.001). Conclusion: For the first time, this study demonstrates that at realistic perilymph viscosities, quasistatic pressure forces minimally affect the total insertion force profile during insertion. Mixed friction is the main determinant, and significantly decreases with increaseing insertion speeds. This suggests that in clinical settings with similar ST geometries and surgical preparation, quasistatic pressure plays a subordinate role. Moreover, the findings indicate that managing the hydrodynamics of the cochlear environment, possibly through pre-surgical preparation or the use of specific lubricants, could effectively reduce insertion forces.
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Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts.
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Ácido Araquidônico , Ferroptose , Ferroptose/efeitos dos fármacos , Ácido Araquidônico/metabolismo , Ácido Araquidônico/farmacologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linhagem Celular Tumoral , Água/química , Solubilidade , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/genética , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/efeitos dos fármacosRESUMO
Purpose: The significance of atraumatic electrode array (EA) insertion in cochlear implant (CI) surgery is widely acknowledged, with consensus that forces due to EA insertion are directly correlated with insertion trauma. Unfortunately, the manual perception of these forces through haptic feedback is inherently limited, and techniques for in vivo force measurements to monitor the insertion are not yet available. Addressing this gap, we developed of a force-sensitive insertion tool capable of capturing real-time insertion forces during standard CI surgery. Methods: This paper describes the tool and its pioneering application in a clinical setting and reports initial findings from an ongoing clinical study. Data and experiences from five patients have been evaluated so far, including force profiles of four patients. Results: The initial intraoperative experiences are promising, with successful integration into the conventional workflow. Feasibility of in vivo insertion force measurement and practicability of the tool's intraoperative use could be demonstrated. The recorded in vivo insertion forces show the expected rise with increasing insertion depth. Forces at the end of insertion range from 17.2 mN to 43.6 mN, while maximal peak forces were observed in the range from 44.8 mN to 102.4 mN. Conclusion: We hypothesize that this novel method holds the potential to assist surgeons in monitoring the insertion forces and, thus, minimizing insertion trauma and ensuring better preservation of residual hearing. Future data recording with this tool can form the basis of ongoing research into the causes of insertion trauma, paving the way for new and improved prevention strategies.
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AIMS: Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. METHODS AND RESULTS: A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001). CONCLUSION: Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.
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Neutrófilos/enzimologia , Peroxidase/deficiência , Sistema Vasomotor/enzimologia , Adulto , Idoso , Animais , Velocidade do Fluxo Sanguíneo , Circulação Coronária/fisiologia , Endotélio Vascular/enzimologia , Hemodinâmica/fisiologia , Humanos , Masculino , Artéria Torácica Interna/fisiologia , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Ativação de Neutrófilo , Nicotina/farmacologia , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Peroxidase/farmacologia , Sus scrofa , Vasodilatação/fisiologia , Adulto JovemRESUMO
PURPOSE: The trajectory along which the cochlear implant electrode array is inserted influences the insertion forces and the probability for intracochlear trauma. Controlling the trajectory is especially relevant for reproducible conditions in electrode insertion tests. Using ex vivo cochlear specimens, manual alignment of the invisibly embedded cochlea is imprecise and hardly reproducible. The aim of this study was to develop a method for creating a 3D printable pose setting adapter to align a specimen along a desired trajectory toward an insertion axis. METHODS: Planning points of the desired trajectory into the cochlea were set using CBCT images. A new custom-made algorithm processed these points for automated calculation of a pose setting adapter. Its shape ensures coaxial positioning of the planned trajectory to both the force sensor measuring direction and the insertion axis. The performance of the approach was evaluated by dissecting and aligning 15 porcine cochlear specimens of which four were subsequently used for automated electrode insertions. RESULTS: The pose setting adapter could easily be integrated into an insertion force test setup. Its calculation and 3D printing was possible in all 15 cases. Compared to planning data, a mean positioning accuracy of 0.21 ± 0.10 mm at the level of the round window and a mean angular accuracy of 0.43° ± 0.21° were measured. After alignment, four specimens were used for electrode insertions, demonstrating the practical applicability of our method. CONCLUSION: In this work, we present a new method, which enables automated calculation and creation of a ready-to-print pose setting adapter for alignment of cochlear specimens in insertion test setups. The approach is characterized by a high level of accuracy and reproducibility in controlling the insertion trajectory. Therefore, it enables a higher degree of standardization in force measurement when performing ex vivo insertion tests and thereby improves reliability in electrode testing.
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PURPOSE: Trauma that may be inflicted to the inner ear (cochlea) during the insertion of an electrode array (EA) in cochlear implant (CI) surgery can significantly decrease the hearing outcome of patients with residual hearing. Interaction forces between the EA and the cochlea are a promising indicator for the likelihood of intracochlear trauma. However, insertion forces have only been measured in laboratory setups. We recently developed a tool to measure the insertion force during CI surgery. Here, we present the first ex vivo evaluation of our tool with a focus on usability in the standard surgical workflow. METHODS: Two CI surgeons inserted commercially available EAs into three temporal bone specimens. The insertion force and the orientation of the tool were recorded together with camera footage. The surgeons answered a questionnaire after each insertion to evaluate the surgical workflow with respect to CI surgery. RESULTS: The EA insertion using our tool was rated successful in all 18 trials. The surgical workflow was evaluated to be equivalent to standard CI surgery. Minor handling challenges can be overcome through surgeon training. The peak insertion forces were 62.4 mN ± 26.7 mN on average. Peak forces significantly correlated to the final electrode insertion depth, supporting the assumption that the measured forces mainly correspond to intracochlear events and not extracochlear friction. Gravity-induced forces of up to 28.8 mN were removed from the signal, illustrating the importance of the compensation of such forces in manual surgery. CONCLUSION: The results show that the tool is ready for intraoperative use. In vivo insertion force data will improve the interpretability of experimental results in laboratory settings. The implementation of live insertion force feedback to surgeons could further improve residual hearing preservation.