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Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes.
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The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation.
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Aneurisma Roto , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/fisiopatologia , Masculino , Feminino , Aneurisma Roto/fisiopatologia , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Idoso , Adulto , Fatores de Risco , Modelos Cardiovasculares , Artéria Cerebral Média/fisiopatologiaRESUMO
STUDY DESIGN: A laboratory study comparing polyether ether ketone (PEEK)-zeolite and PEEK spinal implants in an ovine model. OBJECTIVE: This study challenges a conventional spinal implant material, PEEK, to PEEK-zeolite using a nonplated cervical ovine model. SUMMARY OF BACKGROUND DATA: Although widely used for spinal implants due to its material properties, PEEK is hydrophobic, resulting in poor osseointegration, and elicits a mild nonspecific foreign body response. Zeolites are negatively charged aluminosilicate materials that are hypothesized to reduce this pro-inflammatory response when used as a compounding material with PEEK. MATERIALS AND METHODS: Fourteen skeletally mature sheep were, each, implanted with one PEEK-zeolite interbody device and one PEEK interbody device. Both devices were packed with autograft and allograft material and randomly assigned to one of 2 cervical disc levels. The study involved 2 survival time points (12 and 26 weeks) and biomechanical, radiographic, and immunologic endpoints. One sheep expired from complications not related to the device or procedure. A biomechanical evaluation was based on measures of segmental flexibility, using 6 degrees of freedom pneumatic spine tester. Radiographic evaluation was performed using microcomputed tomography scans in a blinded manner by 3 physicians. Levels of the pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha at the implant, were quantified using immunohistochemistry. RESULTS: PEEK-zeolite and PEEK exhibited an equivalent range of motion in flexion extension, lateral bending, and axial torsion. A motion was significantly reduced for implanted devices at both time points as compared with native segments. Radiographic assessments of fusion and bone formation were similar for both devices. PEEK-zeolite exhibited lower levels of IL-1ß ( P = 0.0003) and IL-6 ( P = 0.03). CONCLUSION: PEEK-zeolite interbody fusion devices provide initial fixation substantially equivalent to PEEK implants but exhibit a reduced pro-inflammatory response. PEEK-zeolite devices may reduce the chronic inflammation and fibrosis previously observed with PEEK devices.
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Fusão Vertebral , Zeolitas , Animais , Ovinos , Microtomografia por Raio-X/métodos , Interleucina-6 , Polietilenoglicóis/química , Cetonas/química , Éteres , Fusão Vertebral/métodos , Fenômenos BiomecânicosRESUMO
Introduction The geriatric population is the fastest growing segment of the American population, and octogenarians are increasingly seen by neurosurgeons for relatively common lesions such as meningiomas. Unfortunately, providers do not have clear data to guide decision-making regarding these lesions, particularly if they involve the skull base. Current research in outcomes among the elderly looks at a wide range of ages, often anyone older than 65. Previous studies in octogenarians report a wide-range of mortality rates and do not focus on skull base lesions. This paper strives to clarify the experiences and outcomes of octogenarians. Patients and Methods This retrospective series reviews skull base tumor surgeries performed at a single academic institution over the past 15 years in octogenarian patients. Primary endpoint was 30-day mortality; however, potential risk factors, perioperative morbidity, postdischarge disposition, and longer term follow-up were also captured. Multivariate logistic regression was performed to identify relevant perioperative and medical characteristics that increases the risk of adverse events. Results Fourteen patients underwent craniotomies for skull base procedures with an average age of 84.5, with a 14% 30-day mortality rate. One patient required a tracheostomy on discharge and approximately half were able to either go home or rehabilitation after their procedure. On statistical analysis, there were no noted characteristics that predisposed any of the patients to a poorer outcome. Conclusion Octogenarian patients were able to tolerate surgery for skull base meningiomas resection. This outcome data may be used to inform surgical decision and guide conversation with patients and their families.
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PURPOSE: Complications related to vascular damage such as intra-operative bleeding may be avoided during neurosurgical procedures such as petroclival meningioma surgery. To address this and improve the patient's safety, we designed a real-time blood vessel avoidance strategy that enables operation on deformable tissue during petroclival meningioma surgery using Micron, a handheld surgical robotic tool. METHODS: We integrated real-time intra-operative blood vessel segmentation of brain vasculature using deep learning, with a 3D reconstruction algorithm to obtain the vessel point cloud in real time. We then implemented a virtual-fixture-based strategy that prevented Micron's tooltip from entering a forbidden region around the vessel, thus avoiding damage to it. RESULTS: We achieved a median Dice similarity coefficient of 0.97, 0.86, 0.87 and 0.77 on datasets of phantom blood vessels, petrosal vein, internal carotid artery and superficial vessels, respectively. We conducted trials with deformable clay vessel phantoms, keeping the forbidden region 400 [Formula: see text]m outside and 400 [Formula: see text]m inside the vessel. Micron's tip entered the forbidden region with a median penetration of just 8.84 [Formula: see text]m and 9.63 [Formula: see text]m, compared to 148.74 [Formula: see text]m and 117.17 [Formula: see text]m without our strategy, for the former and latter trials, respectively. CONCLUSION: Real-time control of Micron was achieved at 33.3 fps. We achieved improvements in real-time segmentation of brain vasculature from intra-operative images and showed that our approach works even on non-stationary vessel phantoms. The results suggest that by enabling precise, real-time control, we are one step closer to using Micron in real neurosurgical procedures.
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Neoplasias Meníngeas , Meningioma , Algoritmos , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Imagens de FantasmasRESUMO
BACKGROUND: Bleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability. OBJECTIVE: To develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population. METHODS: Cross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy. RESULTS: The final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%). CONCLUSIONS: Based on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.
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Aneurisma Roto , Aneurisma Intracraniano , Humanos , Aneurisma Roto/epidemiologia , Estudos Transversais , Hemodinâmica , Hidrodinâmica , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Aprendizado de MáquinaRESUMO
BACKGROUND: Blebs are rupture risk factors in intracranial aneurysms (IAs), but their prevalence, distribution, and associations with clinical factors as well as their causes and effects on aneurysm vulnerability remain unclear. METHODS: A total of 122 blebs in 270 IAs selected for surgery were studied using patient-specific vascular reconstructions from 3D angiographic images. Bleb geometry, location on the aneurysm, and frequency of occurrence in aneurysms at different locations were analyzed. Associations between gender, age, smoking, hypertension, hormone therapy, dental infection, and presence of blebs were investigated. RESULTS: Of all aneurysms with blebs, 77% had a single bleb and 23% had multiple blebs. Only 6% of blebs were at the neck, while 46% were in the body and 48% in the dome. Aneurysms with blebs were larger (p<0.0001), more elongated (p=0.0002), and with wider necks than aneurysms without blebs. Bleb presence was associated with dental infection (p=0.0426) and negatively associated with hormone therapy (p=0.0426) in women. Anterior and posterior communicating arteries had larger percentages of aneurysms with blebs than internal carotid arteries. Patients with a history of hypertension tended to have a larger percentage of aneurysms with blebs. However, these trends did not reach significance in this sample. CONCLUSIONS: Blebs are common in IAs, and most aneurysms harboring blebs have a single bleb. Blebs in the aneurysm neck are rare, but they are equally common in the body and dome. The presence of blebs in IAs was associated with dental infection, and negatively associated with hormone replacement therapy.
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Aneurisma Roto , Aneurisma Intracraniano , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Artéria Carótida Interna/fisiopatologia , Angiografia Cerebral/métodos , Hipertensão/diagnóstico por imagem , Hipertensão/epidemiologia , Hipertensão/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Prevalência , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
BACKGROUND: Blebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites. METHODS: Blebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs. RESULTS: Thin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%. CONCLUSIONS: Not all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.
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Aneurisma Roto , Hemodinâmica , Hidrodinâmica , Aneurisma Intracraniano , Feminino , Humanos , Masculino , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/fisiopatologia , Aneurisma Roto/cirurgia , Hemodinâmica/fisiologia , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Fatores de Risco , Estresse MecânicoRESUMO
STUDY DESIGN: A comparative biomechanical human cadaveric spine study of a dynamic fusion rod and a traditional titanium rod. OBJECTIVE: The purpose of this study was to measure and compare the biomechanical metrics associated with a dynamic fusion device, Isobar TTL Evolution, and a rigid rod. SUMMARY OF BACKGROUND DATA: Dynamic fusion rods may enhance arthrodesis compared with a rigid rod. Wolff's law implies that bone remodeling and growth may be enhanced through anterior column loading (AL). This is important for dynamic fusion rods because their purpose is to increase AL. METHODS: Six fresh-frozen lumbar cadaveric specimens were used. Each untreated specimen (Intact) underwent biomechanical testing. Next, each specimen had a unilateral transforaminal lumbar interbody fusion performed at L3-L4 using a cage with an integrated load cell. Pedicle screws were also placed at this time. Subsequently, the Isobar was implanted and tested, and finally, a rigid rod replaced the Isobar in the same pedicle screw arrangement. RESULTS: In terms of range of motion, the Isobar performed comparably to the rigid rod and there was no statistical difference found between Isobar and rigid rod. There was a significant difference between the intact and rigid rod and also between intact and Isobar conditions in flexion extension. For interpedicular displacement, there was a significant increase in flexion extension (P=0.017) for the Isobar compared with the rigid rod. Isobar showed increased AL under axial compression compared with the rigid rod (P=0.024). CONCLUSIONS: Isobar provided comparable stabilization to a rigid rod when using range of motion as the metric, however, AL was increased because of the greater interpedicular displacement of dynamic rod compared with a rigid rod. By increasing interpedicular displacement and AL, it potentially brings clinical benefit to procedures relying on arthrodesis.
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Vértebras Lombares/fisiologia , Parafusos Pediculares , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Cadáver , Humanos , Fixadores Internos , Região Lombossacral , RotaçãoRESUMO
OBJECT: The term VACTERL represents a nonrandom association of birth defects including vertebral malformations, anal atresia, cardiac anomalies, tracheoesophageal fistulas (TEFs), renal anomalies, and limb malformations. Clinical experience and a few published case series suggest that a tethered spinal cord (TSC) occurs commonly in children with VACTERL, but to date, no study has defined the prevalence of TSC in patients with VACTERL. Such information would guide decisions about the appropriateness of screening spinal imaging. METHODS: The authors reviewed the charts of all patients discharged from the neonatal intensive care unit at Children's Hospital Pittsburgh in the past 14 years with the diagnosis of VACTERL, TEF, or anal atresia. During that period, the authors' protocol has been to use spinal ultrasound to screen this population for TSC. The charts were reviewed for the presence of a TSC requiring surgery and for the features of VACTERL. RESULTS: Thirty-three patients with VACTERL and adequate spinal imaging studies were identified. In 13 (39%) of these, a TSC requiring surgery was identified. Among patients without VACTERL, the incidence of TSC was 7.9% in those with anal atresia and 2.4% in those with TEF. False-negative ultrasounds were identified in 21.4% of patients with TSC. CONCLUSIONS: Children with VACTERL should undergo MR imaging screening for TSC. In infants with anal atresia without VACTERL, the incidence of TSC is much lower than in those with VACTERL.