Clinical Effectiveness of Percutaneous Epidural Neuroplasty According to the Type of Single-Level Lumbar Disc Herniation : A 12-Month Follow-Up Study

Objective: To determine whether the outcomes of percutaneous epidural neuroplasty (PEN) are influenced by the type of lumbar disc herniation (LDH) and evaluate the effectiveness of PEN in patients with single-level LDH. Methods: This study included 430 consecutive patients with single-level LDH who underwent PEN. Before treatment, the LDH type was categorized as bulging, protrusion, extrusion, and sequestration, while Pfirrmann grades were assigned according to imaging findings. Visual analog scale (VAS) scores for back and leg pain and success rates (Odom's criteria) were assessed at 1, 3, 6, and 12 months after treatment. Results: The mean preoperative VAS scores for back and leg pain were 6.90 and 4.23, respectively; these decreased after PEN as follows : 2.25 and 1.45, respectively, at 1 month; 2.61 and 1.68, respectively, at 3 months; 2.28 and 1.48, respectively, at 6 months; and 2.88 and 1.48, respectively, at 12 months (p70% patients with extrusion or sequestration. Patients with Pfirrmann grades 1-3 (14.0-21.5%) showed a significantly higher rate of subsequent surgery than those with Pfirrmann grade 0 (4.9%; p<0.05). Conclusion: Our findings suggest that PEN is an effective treatment for back and leg pain caused by single-level LDH, with the outcomes remaining unaffected by the LDH type.ope

Efficacy of a Novel Annular Closure Device After Lumbar Discectomy in Korean Patients : A 24-Month Follow-Up of a Randomized Controlled Trial

Objective: Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH); however, up to 2-18% of patients with LDH have experienced recurrent disc herniation. The purpose of this study was to evaluate the efficacy of a novel annular closure device (ACD) for preventing LDH recurrence and re-operation compared with that of conventional lumbar discectomy (CLD). Methods: In this prospective randomized controlled trial, we compared CLD with discectomy utilizing the Barricaid® (Intrinsic Therapeutics, Inc., Woburn, MA, USA) ACD. Primary radiologic outcomes included disc height, percentage of preoperative disc height maintained, and re-herniation rates. Additional clinical outcomes included visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and 12-item short-form health survey (SF-12) quality of life scores. Outcomes were measured at preoperation and at 1 week, 1, 3, 6, 12, and 24 months postoperation. Results: Sixty patients (30 CLD, 30 ACD) were enrolled in this study. At 24-month follow-up, the disc height in the ACD group was significantly greater than that in the CLD group (11.4±1.5 vs. 10.2±1.2 mm, p=0.006). Re-herniation occurred in one patient in the ACD group versus six patients in the CLD group (χ2=4.04, p=0.044). Back and leg VAS scores, ODI scores, and SF-12 scores improved significantly in both groups compared with preoperative scores in the first 7 days following surgery and remained at significantly improved levels at a 24-month follow-up. However, no statistical difference was found between the two groups. Conclusion: Lumbar discectomy with the Barricaid® (Intrinsic Therapeutics, Inc.) ACD is more effective at maintaining disc height and preventing re-herniation compared with conventional discectomy. Our results suggest that adoption of ACD in lumbar discectomy can help improve the treatment outcome.ope

심폐소생술에 대한 수학적 모델링 기반의 접근

학위논문(박사) -- 서울대학교대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021.8. 이정찬.심폐소생술의 생리학적 현상에 대한 이해를 위해 심폐소생술의 메커니즘과 이를 기반으로 한 수학적 모델링에 대한 연구들이 많이 진행되어왔다. 하지만, 기존의 수학적 모델이 아직까지 심폐소생술 중의 혈역학적 현상을 제대로 반영하지 못하고 있는 부분이 있다. 또한, 최근 심폐소생술 연구의 방향성은 환자 맞춤형으로 나아가고 있다. 하지만, 환자 맞춤형 심폐소생술은 환자 개인의 요소 및 주변 환경 요소들의 영향을 받기 때문에 임상환경에서 접근하는 것이 쉽지 않다. 따라서, 본 연구는 시뮬레이션 기반의 이론적 연구를 통해 심폐소생술 중의 혈역학에 대한 이해와 통찰력을 제공하고자 3가지 목표를 기반으로 연구를 수행하였다. 첫번째는 현재 심폐소생술의 혈역학적 현상을 반영할 수 있는 개선된 일반화된 심폐소생모델을 개발하는 것을 목표로 하였다. 본 연구에서 제안하는 개선된 심폐소생모델은 기존 모델에 상대정맥과 하대정맥 구획을 추가하였고, “하이브리드 펌프” 메커니즘을 적용하였다. 기존 모델과 개선된 모델의 혈역학적인 현상을 비교하기 위해 다양한 기법에 대한 시뮬레이션 및 동물 모델로부터 얻은 데이터를 비교하였다. 동물 모델과 기존 모델, 개선한 모델의 압력 곡선 및 관상동맥관류압 등을 비교한 결과, 본 연구에서 개선한 모델이 현재의 심폐소생술 메커니즘을 더 잘 반영하는 심폐소생모델임을 검증하였다. 두 번째 목표는 개선한 모델을 기반으로 현재의 심폐소생술 방법으로부터 발생하는 이슈인 흉강의 탄성력 감소에 의한 부정적인 영향과 최적의 압박 위치에 대해 시뮬레이션을 통해 혈역학적인 해석을 제공하고자 하였다. 결과에서 흉강의 탄성력이 감소함에 따라 압박 중 최대 압력이 감소하며, 정맥 복귀 및 혈류 역시 감소하는 결과를 보였다. 압박 위치 변화는 심실과 심방의 압박 비율을 조절하여 시뮬레이션을 수행하였다. 이 결과에서 심실보다 심방이 더 많이 압박될 경우 1회 박출량 및 관상동맥 관류 압이 감소하면서 혈역학이 제한되는 결과를 보여주었다. 따라서, 압박 중 최대 압력 변화와 관상동맥관류압의 변화는 흉강의 탄성력 변화 추정 및 압박 위치 가이드를 해줄 수 있는 잠재력을 가질 수 있음을 입증하였다. 마지막으로 환자 맞춤형 심폐소생술모델의 가능성을 제시하고자 하였다. 본 연구에서는 유전자 알고리즘을 통해 환자 개별에 대한 심혈관계 파라미터를 추정하였고, 환자마다 다른 심혈관계 파라미터 세트를 가짐으로써 맞춤형 심혈관계 모델을 구성할 수 있음을 검증하였다. 또한, 맞춤형 심혈관계 모델에 심폐소생모델을 적용하여 심혈관계 파라미터 구성에 따라 흉부 압박 시 혈역학적 영향이 달라짐을 검증하였다. 추가적으로 돼지 모델에서 다양한 압박 조건 변화에 대한 혈역학적 변화를 비교하였고, 이를 통해 맞춤형 모델을 통해 최적의 혈역학적 효과를 갖는 압박 조건을 제시할 수 있음을 보였다. 결론적으로 본 연구를 통해 제안하는 심폐소생 모델이 현재 심폐소생술에 의한 메커니즘을 더 잘 반영하는 일반화된 모델임을 보여주었고, 이를 통해 현재 심폐소생술 방법에 의한 이슈에 대해서 혈역학적인 해석이 가능함을 입증하였다. 또한, 이를 기반으로 환자 맞춤형 심폐소생 모델의 가능성 제시함으로써 맞춤형 심폐소생 모델링에 대한 연구의 기반이 될 수 있음을 보여주었다.For a long time, many studies based on mathematical modeling have been conducted to understand cardiopulmonary resuscitation (CPR) physiology. However, some aspects of the existing CPR model do not reflect the current CPR physiology appropriately. If the generalized CPR model does not suitably reflect the hemodynamic phenomena of current CPR, errors may exist in the hemodynamic interpretation. In addition, it is suggested that the one-size-fits-all CPR specified in the guidelines is not suitable, and the direction of recent CPR research is shifting toward personalized CPR. However, in personalized CPR, it is difficult to use preclinical or clinical trial approaches because various factors associated with the patient and environment interact and affect the patient. Therefore, this study was conducted with three goals to provide insight into the hemodynamics during CPR through a simulation-based approach. The first objective was to develop an improved generalized CPR model that can reflect the current CPR physiology. The modified CPR model proposed herein added superior and inferior vena cava compartments in the thoracic cavity of the existing model, as well as a “hybrid pump” mechanism. To compare the hemodynamic effects of the existing and modified models, various maneuvers such as the active compression-decompression CPR combined with the impedance threshold device, head-up tilt, and head-down tilt were simulated. Additionally, the modified model was compared with an animal model to confirm that it reflects the current CPR physiology more than the existing model does. The comparison showed that the pressure waveform and coronary perfusion pressure (CPP) were more appropriately reflected than in the existing model. Therefore, it was verified that the improved model developed in this study is a generalized CPR model that reflects the current CPR physiology more accurately. The second goal was to verify the hemodynamic effects on the reduced thoracic elasticity and compression position—which are the current issues of the existing CPR technique—through simulation based on the improved model. The reduced elasticity of the thorax was simulated to decrease linearly for 1 min immediately after the start of CPR. The results show that as the elasticity of the thorax decreased, the pressure amplitude of the aorta and vena cava decreased during compression, along with the venous return and blood flow. Furthermore, a simple simulation was performed by adjusting the compression ratio between the ventricle and atrium with the thoracic pump factor to compare the hemodynamic difference according to the compression position. Consequently, when the atrium was compressed more than the ventricle, the stroke volume and CPP decreased, indicating that hemodynamics was limited. Therefore, it was demonstrated that a change in the pressure amplitude and CPP during compression could potentially enable estimation of the change in the elasticity of the thorax and assist in determining the position of compression. Finally, this study attempted to present the possibility of a personalized CPR model. Cardiovascular parameters were estimated for different patients using a genetic algorithm. Additionally, it was confirmed that patient-specific cardiovascular models could be constructed with different sets of parameters for each patient. Furthermore, incorporating the CPR model into the patient-specific cardiovascular model revealed that the hemodynamic effect of chest compression varies according to the cardiovascular parameter configuration. The hemodynamic changes for different compression conditions were compared in a pig model. From the results, it was shown that various hemodynamics occurred depending on the compression condition when using the personalized CPR model. Thus, it is possible to determine the optimal compression condition for the patient-specific from this. In conclusion, this study showed that the modified CPR model is a generalized model that reflects the current CPR physiology more accurately. It also proved that hemodynamic interpretation can address the limitations of the current CPR technique through the modified model. Additionally, by presenting the possibility of a patient-specific CPR model based on this, this study can serve as the basis for research on personalized CPR modeling.Chapter 1. Introduction 1 1.1 Basic understanding of cardiovascular system 2 1.1.1 Cardiac output 2 1.1.2 Venous return and Frank-Starling law 5 1.1.3 Blood circulatory system 7 1.2 Cardiopulmonary resuscitation (CPR) 10 1.2.1 Basic concept for CPR 10 1.2.2 Theories for CPR mechanism 13 1.3 Mathematical modeling for CPR 15 1.3.1 Basic concept of lumped parameter model for cardiovascular system 15 1.3.2 Previous studies on CPR modeling 20 1.4 Motivation and objectives 22 Chapter 2. Materials and Methods 29 2.1 Modified CPR model for general CPR model 30 2.1.1 Modified hybrid CPR model 30 2.1.2 Simulations of various maneuvers for CPR model 35 2.1.2.1 Active compression-decompression CPR with an impedance threshold valve (ACD-CPR+ITV) 35 2.1.2.2 Head-up tilt (HUT) and head-down tilt (HDT) 37 2.1.3 Animal experiments for hemodynamic data acquisition 39 2.1.3.1 Experimental protocol 40 2.1.3.2 Data acquisition 41 2.2 Simulation-based approach to current issues in CPR using modified hybrid CPR model 42 2.2.1 Reduced elasticity of thorax 42 2.2.1 Ventricle-atrium compression ratio (VAR) for compression position 43 2.3 Parameter estimation of simple cardiovascular model for patient-specific CPR model 45 2.3.1 Simple cardiovascular model 45 2.3.2 Genetic algorithm for parameter estimation 47 2.3.3 Application of CPR model to patient-specific cardiovascular model 49 Chapter 3. Results and Discussion 51 3.1 Modified CPR model based on general CPR model 52 3.1.1 Comparison results of animal experiments and simulations 54 3.1.2 Hemodynamic effects on the various maneuvers 58 3.1.2.1 Comparison of CPR techniques 58 3.1.2.2 HUT and HDT 60 3.2 Simulation-based approach to current issues in CPR using modified CPR model 64 3.2.1 Hemodynamic effects on reduced elasticity of thorax 64 3.2.2 Coronary perfusion pressure for various VAR 68 3.3 Parameter estimation of simple cardiovascular model for patient-specific CPR model 72 3.3.1 Verification of parameter estimation using open dataset 74 3.3.2 Application to patient-specific CPR model 88 3.4 Limitations 100 Chapter 4. Conclusion 102 4.1 Dissertation summary 103 4.2 Future works 105 References 107 Abstract in Korean 117 Acknowledgement 119 감사의 글 120박

The Risk Factors Associated With Delirium After Lumbar Spine Surgery in Elderly Patients

Background: To prospectively explore the incidence and risk factors for postoperative delirium in elderly patients following lumbar spine surgery. Methods: This prospective study enrolled 148 consecutive patients over the age of 65 who were scheduled to undergo spine surgery. Patients were screened for delirium using the short Confusion Assessment Method (CAM) postoperatively. Patient demographics and relevant medical information were collected. Logistic regression analysis was used to identify the risk factors associated with postoperative delirium. Results: Eighty-three patients (56.1%) who underwent lumbar spine surgery (not coexisting with cervical or thoracic spine surgery) were enrolled in our study. Post-operative delirium was noted in 14.5% of patients over 65 years old. The presence of preoperative Parkinsonism was significantly higher in the delirium group (41.7% vs. 8.5%, P=0.002), as was a higher preoperative C-reactive protein (CRP) (7.0±15.2 vs. 1.3±2.3 mg/L, P=0.017) when compared with the non-delirium group. Of the risk factors, male sex [odds ratio (OR) =0.10, 95% confidence interval (CI): 0.01-0.66, P=0.017], Parkinsonism (OR =5.83, 95% CI: 1.03-32.89, P=0.046), and lower baseline MMSE score (OR =0.71, 95% CI: 0.52-0.97, P=0.032) were independently associated with postoperative delirium in elderly patients undergoing lumbar spine surgery. Conclusions: Post-operative delirium occurred in 14.5% of elderly patients who underwent lumbar spine surgery. Male sex, Parkinsonism, and lower baseline MMSE score were identified as independent risk factors for postoperative delirium in elderly patients following lumbar surgery.ope

Influence of Diabetes Mellitus on Patients With Lumbar Spinal Stenosis: A Nationwide Population-Based Study

Purpose: To evaluate the relationship between comorbidities, medical cost, and surgical outcome in patients with lumbar spinal stenosis (LSS) and diabetes mellitus (DM). Methods: Data on patients with LSS (n = 14,298) were collected from the Korean National Health Insurance Service database from 2005 to 2007. After 8 years of follow-up, a "DM group" (n = 3,478) and a "non-DM group" (n = 10,820) were compared according to outcome measures. Cox proportional hazard regressions were performed to examine the relationship between DM, hypertension (HTN), cardiovascular disease (CVD), chronic kidney disease (CKD), cerebrovascular disease (CbVD), and surgery for LSS. The admission rate and medical cost as well asthe overall survival rate for those who underwent lumbar surgery were also assessed among patients with DM and LSS. Results: Mortality was about 1.35 times higher in the DM group than in the non-DM group. Patients with DM and comorbidities including HTN (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.25-1.56; p<0.001), CVD (HR, 1.53; 95% CI, 1.36-1.73; p<0.001), CKD (HR, 3.18; 95% CI, 2.7-3.76; p<0.001), and CbVD (HR, 1.69; 95% CI, 1.49-1.91; p<0.001) showed an increased risk of mortality. The mean hospitalization time and average medical cost of patients with DM who underwent lumbar surgery were 60.8 days, and 7,127 USD, respectively. This was 31.3 days longer, and 6,207 USD higher, respectively, than those of patients with DM who underwent conservative treatment for LSS. Within the DM group, the survival rate of surgical management of LSS had a significant tendency for positive prognosis compared with those administered conservative treatment (p = 0.046). Conclusions: In patients with LSS, DM was associated both with poor prognosis (most significantly in those with CKD), and increased medical cost in those who underwent surgery. Nevertheless, surgical treatment for LSS in patients with DM was related to favorable prognosis compared with conservative treatment.ope

Biomechanical Analysis of Biodegradable Cervical Plates Developed for Anterior Cervical Discectomy and Fusion

STUDY DESIGN: In-vitro biomechanical investigation. PURPOSE: To evaluate the biomechanical effects of the degeneration of the biodegradable cervical plates developed for anterior cervical discectomy and fusion (ACDF) on fusion and adjacent levels. OVERVIEW OF LITERATURE: Biodegradable implants have been recently introduced for cervical spine surgery. However, their effectiveness and safety remains unclear. METHODS: A linear three-dimensional finite element (FE) model of the lower cervical spine, comprising the C4-C6 vertebrae was developed using computed tomography images of a 46-year-old woman. The model was validated by comparison with previous reports. Four models of ACDF were analyzed and compared: (1) a titanium plate and bone block (Tita), (2) strong biodegradable plate and bone block (PLA-4G) that represents the early state of the biodegradable plate with full strength, (3) weak biodegradable plate and bone block (PLA-1G) that represents the late state of the biodegradable plate with decreased strength, and (4) stand-alone bone block (Bloc). FE analysis was performed to investigate the relative motion and intervertebral disc stress at the surgical (C5-C6 segment) and adjacent (C4-C5 segment) levels. RESULTS: The Tita and PLA-4G models were superior to the other models in terms of higher segment stiffness, smaller relative motion, and lower bone stress at the surgical level. However, the maximal von Mises stress at the intervertebral disc at the adjacent level was significantly higher in the Tita and PLA-4G models than in the other models. The relative motion at the adjacent level was significantly lower in the PLA-1G and Bloc models than in the other models. CONCLUSIONS: The use of biodegradable plates will enhance spinal fusion in the initial stronger period and prevent adjacent segment degeneration in the later, weaker period.ope

Biomechanical Comparison of Spinal Fusion Methods Using Interspinous Process Compressor and Pedicle Screw Fixation System Based on Finite Element Method

OBJECTIVE: To investigate the biomechanical effects of a newly proposed Interspinous Process Compressor (IPC) and compare with pedicle screw fixation at surgical and adjacent levels of lumbar spine. METHODS: A three dimensional finite element model of intact lumbar spine was constructed and two spinal fusion models using pedicle screw fixation system and a new type of interspinous devices, IPC, were developed. The biomechanical effects such as range of motion (ROM) and facet contact force were analyzed at surgical level (L3/4) and adjacent levels (L2/3, L4/5). In addition, the stress in adjacent intervertebral discs (D2, D4) was investigated. RESULTS: The entire results show biomechanical parameters such as ROM, facet contact force, and stress in adjacent intervertebral discs were similar between PLIF and IPC models in all motions based on the assumption that the implants were perfectly fused with the spine. CONCLUSION: The newly proposed fusion device, IPC, had similar fusion effect at surgical level, and biomechanical effects at adjacent levels were also similar with those of pedicle screw fixation system. However, for clinical applications, real fusion effect between spinous process and hooks, duration of fusion, and influence on spinous process need to be investigated through clinical study.ope

Diagnostic Relevance of Pressure-Controlled Discography

Discogenic pain is a leading cause of chronic low back pain. The authors investigated the efficacy of pressure-controlled discography to determine its role in clinical decision-making for the management of patients with discogenic pain. Pressure-controlled discography was performed in 21 patients (51 discs) with pain-provocation, followed by post-discography computerized tomography scans. Pain response was classified as positive response and negative response, and measured with visual analog scale scores. Discographic findings were graded by the modified Dallas discogram scale. Elastance, pain provocation on intradiscal pressure, pressure and volume of initial pain response, and pain response intensity were statistically analyzed. Elastance showed significant differences between Grade 0 and Grade 4 & 5. Decreased elastance with positive pain response group was a good indicator to imply that disc degeneration presumably is a pain generator. Results of pain response were well correlated with intradiscal pressure but not with the amount of injected volume. Among 31 discs of Grade 4 and 5, 74% showed negative pain response and 26% showed positive response. It was concluded that pressure-controlled discography was useful to diagnose discogenic pain and excellent guide in decision-making for spinal operations.ope

Combinatorial physicochemical stimuli in the three-dimensional environment of a hyaluronic acid hydrogel amplify chondrogenesis by stimulating phosphorylation of the Smad and MAPK signaling pathways

The chondrogenesis of stem cells and cartilage tissue regeneration are more efficient in a three-dimensional (3D) environment than in a two-dimensional (2D) environment. Although extensive studies have examined the effects of biochemical or physical cues alone, it is not fully understood how these biochemical and biophysical cues in the 3D environment are intertwined and orchestrated with chondrogenesis for cartilage tissue regeneration. In this study, we used photocrosslinked hyaluronic acid (HA), the extracellular matrix of cartilage, as a general 3D microenvironment to characterize the effects of dimensionality, localization of biochemical cues, regulation of biophysical cues, and external stimulation on chondrogenic signaling pathways in adipose-derived stem cells (hASCs). TGF-β3 was immobilized in HA hydrogels by ionic or covalent conjugation. The stiffness of the hydrogels was tuned by varying the crosslinking density, and an external stimulus for chondrogenesis was provided by ultrasound. The results revealed that the levels of chondrogenic signals in hASCs cultured in the 3D HA hydrogel depended on the presence of TGF-β3, and a reduction in the stiffness of the TGF-β3 covalent conjugated hydrogel increased the chance of interaction with encapsulated hASCs, leading to an increase in chondrogenic signals. External stimulation with ultrasound increased the interaction of hASCs with HA via CD44, thereby increasing chondrogenesis. Our results present a new understanding of the intertwined mechanisms of chondrogenesis in 3D hydrogels connecting TGF-β3 sequestration, mechanical properties, and ultrasound-based external stimulation. Overall, our results suggest that when designing novel biomaterials for tissue engineering, it is necessary to consider the combinatorial mechanism of action in 3D microenvironments.ope

Intradural extramedullary ependymoma with spinal root attachment: a case report

A 36-year-old female patient presented with shoulder pain experienced over a period of one year and progressive weakness in both legs for one month. A magnetic resonance imaging scan revealed an intradural extramedullary (IDEM) fusiform mass about 9.8 cm in length, heterogeneously enhanced at the level of C6-T4 with spinal cord compression. At the time of surgery, the surgeon found an encapsulated IDEM tumor with spinal root attachment. The tumor was completely resected and the histologic diagnosis revealed ependymoma. The patient showed a favorable outcome with no recurrence at the 6-month follow-up. This paper reports a rare case of intradural extramedullary ependymoma with spinal root attachment.ope