Tibia

胫骨
  • 文章类型: Journal Article
    这项研究调查了添加羟基磷灰石纳米颗粒到经过氧化锆喷砂和酸蚀刻(ZiHa)处理的植入物表面的影响,关注低密度骨部位的结构变化和骨愈合参数。使用扫描电子显微镜对具有ZiHa表面和商业改性的氧化锆喷砂和酸蚀刻表面(Zi)的钛圆盘进行了形貌表征,轮廓术,和表面自由能。对于体内评估,22只雌性大鼠切除卵巢,饲养90天,之后,将每组的一个植入物随机放置在动物的每个胫骨干and端。在术后14天和28天进行组织学和免疫组织化学分析(脱钙实验室处理),反向扭矩测试在28天进行,和组织学从钙化实验室处理在60天进行ZiHa组促进表面形态的变化,形成均匀分布的孔隙。为了骨骼愈合,ZiHa表现出更大的反向扭矩,新形成的骨骼区域,和骨/植入物接触值与Zi组相比(p<0.05;t检验)。定性组织学和免疫组织化学分析显示,第14天和第28天ZiHa的骨成熟特征更高。这项临床前研究表明,在氧化锆喷砂和酸蚀表面添加羟基磷灰石可增强卵巢切除大鼠的种植体周围骨愈合。这些发现支持了改善牙科植入物骨整合的潜力,尤其是骨代谢受损的患者。
    This study investigated the impact of adding hydroxyapatite nanoparticles to implant surfaces treated with zirconia blasting and acid etching (ZiHa), focusing on structural changes and bone healing parameters in low-density bone sites. The topographical characterization of titanium discs with a ZiHa surface and a commercially modified zirconia-blasted and acid-etched surface (Zi) was performed using scanning electron microscopy, profilometry, and surface-free energy. For the in vivo assessment, 22 female rats were ovariectomized and kept for 90 days, after which one implant from each group was randomly placed in each tibial metaphysis of the animals. Histological and immunohistochemical analyses were performed at 14 and 28 days postoperatively (decalcified lab processing), reverse torque testing was performed at 28 days, and histometry from calcified lab processing was performed at 60 days The group ZiHa promoted changes in surface morphology, forming evenly distributed pores. For bone healing, ZiHa showed a greater reverse torque, newly formed bone area, and bone/implant contact values compared to group Zi (p < 0.05; t-test). Qualitative histological and immunohistochemical analyses showed higher features of bone maturation for ZiHa on days 14 and 28. This preclinical study demonstrated that adding hydroxyapatite to zirconia-blasted and acid-etched surfaces enhanced peri-implant bone healing in ovariectomized rats. These findings support the potential for improving osseointegration of dental implants, especially in patients with compromised bone metabolism.
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  • 文章类型: Journal Article
    背景:本研究旨在开发一种称为双路径双注意转换器(DDA-Transformer)的新型深度卷积神经网络,旨在实现精确,快速的膝关节CT图像分割,并在机器人辅助的全膝关节置换术(TKA)中进行验证。
    方法:股骨,胫骨,髌骨,和腓骨分割的性能和速度进行了评估,组件尺寸的准确性,在临床上验证了使用该深度学习网络构建的机器人辅助TKA系统的骨切除和对齐.
    结果:总体而言,DDA-Transformer在Dice系数方面优于其他六个网络,在联合上相交,平均表面距离,和Hausdorff距离.DDA-Transformer的分割速度明显快于nnUnet,TransUnet和3D-Unet(p<0.01)。此外,机器人辅助TKA系统在手术准确性方面优于手动组.
    结论:DDA-Transformer在膝关节分割中显示出显着提高的准确性和鲁棒性,这种方便稳定的膝关节CT图像分割网络显著提高了TKA程序的准确性。
    BACKGROUND: This study aimed to develop a novel deep convolutional neural network called Dual-path Double Attention Transformer (DDA-Transformer) designed to achieve precise and fast knee joint CT image segmentation and to validate it in robotic-assisted total knee arthroplasty (TKA).
    METHODS: The femoral, tibial, patellar, and fibular segmentation performance and speed were evaluated and the accuracy of component sizing, bone resection and alignment of the robotic-assisted TKA system constructed using this deep learning network was clinically validated.
    RESULTS: Overall, DDA-Transformer outperformed six other networks in terms of the Dice coefficient, intersection over union, average surface distance, and Hausdorff distance. DDA-Transformer exhibited significantly faster segmentation speeds than nnUnet, TransUnet and 3D-Unet (p < 0.01). Furthermore, the robotic-assisted TKA system outperforms the manual group in surgical accuracy.
    CONCLUSIONS: DDA-Transformer exhibited significantly improved accuracy and robustness in knee joint segmentation, and this convenient and stable knee joint CT image segmentation network significantly improved the accuracy of the TKA procedure.
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  • 文章类型: Journal Article
    经胫骨截肢者肢体体积和形状的变化会影响承窝的贴合性和舒适性。精确测量残肢体积和形状并将其与舒适度相关联的能力可能有助于插座设计和整体护理的进步。这项工作设计并验证了一种新颖的3D激光扫描仪,可以测量残肢的体积和形状。该系统旨在提供准确和可重复的扫描,最小化扫描持续时间,并解释扫描过程中的肢体运动。首先使用具有已知形状的圆柱体对扫描仪进行验证。在静态条件下,平均体积误差为0.17%,对应于0.1毫米的径向空间分辨率。还对胫骨截肢者进行了肢体扫描,五次扫描的标准偏差为8.1ml(0.7%)。和46毫升(4%)的肢体体积的变化时,脱窝后15分钟的站立。
    Changes in limb volume and shape among transtibial amputees affects socket fit and comfort. The ability to accurately measure residual limb volume and shape and relate it to comfort could contribute to advances in socket design and overall care. This work designed and validated a novel 3D laser scanner that measures the volume and shape of residual limbs. The system was designed to provide accurate and repeatable scans, minimize scan duration, and account for limb motion during scans. The scanner was first validated using a cylindrical body with a known shape. Mean volumetric errors of 0.17% were found under static conditions, corresponding to a radial spatial resolution of 0.1 mm. Limb scans were also performed on a transtibial amputee and yielded a standard deviation of 8.1 ml (0.7%) across five scans, and a 46 ml (4%) change in limb volume when the socket was doffed after 15 minutes of standing.
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  • 文章类型: Journal Article
    髌骨是一种临床疾病,其中髌骨相对于股骨滑车定位得太近。这种异常可能导致髌骨不稳定,并容易导致复发性髌股脱位和髌股疼痛。没有结论性的指导方针来确定髌骨位置过高的阈值,已经描述了几种不同的方法来测量髌骨高度。作为一种手术解决方案,胫骨结节截骨术已被描述为纠正髌骨高度过高。在胫骨结节截骨术术后方案的早期阶段,通常使用支具限制负重和膝关节屈曲4-8周,以避免潜在的植入物失败,导致截骨移位或不愈合。与限制康复方案相关的不良反应的潜在风险包括恢复膝关节运动范围的延迟,僵硬和肌肉无力。因此,手术后的恢复会延迟,并可能导致额外的手术和膝关节功能的长期发病。这是一个潜在的,随机化,控制,单盲,单中心试验将新型加速康复方案与传统的,运动限制康复方案。所有35岁及以下的骨骼成熟患者,称为胫骨结节截骨术组,有资格纳入研究。患者将被随机分配到快速康复组或传统康复组。髌骨不稳定的患者将接受内侧髌股韧带重建治疗。该试验的假设是,与保守的康复方案相比,新的加速康复方案将在6、12和24周导致更快的恢复和改善的功能结果。次要假设是两组的并发症发生率相似。该研究将记录短期恢复情况,计划的随访时间为3年。经过1年的随访,试验结果将在同行评审的主要骨科出版物中传播.议定书3.6版,日期:2023年11月28日。
    Patella alta is a clinical condition where the patella is positioned too proximal in relation to the femoral trochlea. Such an abnormality may cause patellar instability and predispose to recurrent patellofemoral dislocations and patellofemoral pain. There are no conclusive guidelines for determining a threshold for too high positioned patella, as several different methods have been described to measure patellar height. As a surgical solution, distalising tibial tubercle osteotomy has been described to correct excessive patellar height. In the early phase of the distalising tibial tubercle osteotomy postoperative protocol, weightbearing and knee flexion are limited with a brace commonly for 4-8 weeks to avoid potential implant failure leading to displacement of the osteotomy or non-union. The potential risks for adverse effects associated with the limitation rehabilitation protocol include a delay in regaining knee range of motion, stiffness and muscle weakness. As a result, recovery from surgery is delayed and may lead to additional procedures and long-term morbidity in knee function. This is a prospective, randomised, controlled, single-blinded, single centre trial comparing a novel accelerated rehabilitation protocol with the traditional, motion restricting rehabilitation protocol. All skeletally mature patients aged 35 years and younger, referred to as the distalising tibial tubercle osteotomy procedure group, are eligible for inclusion in the study. Patients will be randomised to either the fast rehabilitation group or the traditional rehabilitation group. Patients with patellar instability will be additionally treated with medial patellofemoral ligament reconstruction. The hypothesis of the trial is that the novel accelerated rehabilitation protocol will lead to faster recovery and improved functional outcome at 6, 12 and 24 weeks compared with the conservative rehabilitation protocol. A secondary hypothesis is that the complication rate will be similar in both groups. The study will document short-term recovery and the planned follow-up will be 3 years. After the 1-year follow-up, the trial results will be disseminated in a major peer-reviewed orthopaedic publication. Protocol version 3.6, date 28/11/2023.
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  • 文章类型: Journal Article
    背景:这项实验研究旨在直接比较常规和内窥镜辅助刮治(1)残留肿瘤组织(RTT)的数量和(2)在手术时间和外科医生经验水平方面的技术差异。
    方法:三名整形外科医生(受训人员,顾问,高级顾问)在专门准备的皮质-软松质股骨和胫骨锯骨模型上进行了常规(每次4次)和内窥镜辅助刮宫(每次4次)。“肿瘤”由注入到准备好的孔中的不透射线的聚氨酯基泡沫组成。进行介入前和介入后的CT扫描,并在CT扫描上评估RTT。对于统计分析,使用RTT相对于总病变体积的百分比。T-tests,Wilcoxon秩和检验,和Kruskal-Wallis试验用于评估外科医生和外科技术在RTT和时间安排方面的差异。
    结果:总RTT中位数为1%(IQR1-4%)。内镜辅助刮治与较低的RTT(中位数,1%,IQR0-5%)与常规刮宫术(中位数,4%,IQR0-15%,p=0.024)。内镜辅助下的平均手术时间(9.2±2.9分钟)比常规刮宫(5.9±2.0分钟;p=0.004)延长。根据外科医生的经验水平,RTT量(p=0.571)或刮动时间(p=0.251)没有显着差异。
    结论:内镜辅助刮宫术在完全切除组织方面优于常规刮宫术,然而,以延长刮宫时间为代价。在临床实践中,此程序可能保留用于复发风险高的病例(例如解剖学,组织学)。
    BACKGROUND: This experimental study aimed at directly comparing conventional and endoscopic-assisted curettage towards (1) amount of residual tumour tissue (RTT) and (2) differences between techniques regarding surgical time and surgeons\' experience level.
    METHODS: Three orthopaedic surgeons (trainee, consultant, senior consultant) performed both conventional (4x each) and endoscopic-assisted curettages (4x each) on specifically prepared cortical-soft cancellous femur and tibia sawbone models. \"Tumours\" consisted of radio-opaque polyurethane-based foam injected into prepared holes. Pre- and postinterventional CT-scans were carried out and RTT assessed on CT-scans. For statistical analyses, percentage of RTT in relation to total lesion\'s volume was used. T-tests, Wilcoxon rank-sum tests, and Kruskal-Wallis tests were applied to assess differences between surgeons and surgical techniques regarding RTT and timing.
    RESULTS: Median overall RTT was 1% (IQR 1 - 4%). Endoscopic-assisted curettage was associated with lower amount of RTT (median, 1%, IQR 0 - 5%) compared to conventional curettage (median, 4%, IQR 0 - 15%, p = 0.024). Mean surgical time was prolonged with endoscopic-assisted (9.2 ± 2.9 min) versus conventional curettage (5.9 ± 2.0 min; p = 0.004). No significant difference in RTT amount (p = 0.571) or curetting time (p = 0.251) depending on surgeons\' experience level was found.
    CONCLUSIONS: Endoscopic-assisted curettage appears superior to conventional curettage regarding complete tissue removal, yet at expenses of prolonged curetting time. In clinical practice, this procedure may be reserved for cases at high risk of recurrence (e.g. anatomy, histology).
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  • 文章类型: Journal Article
    儿童期和青春期的身体活动(PA)对于最大峰值骨量的积累很重要。对骨骼有益的精确剂量尚不清楚,因为通常用于分析PA数据的方法不适合测量骨骼相关的PA。使用改进的加速度测量方法,这项研究确定了PA的数量和强度与11-12岁儿童的骨结局最密切相关.参与者(n=770;382名男孩)接受了胫骨外周定量计算机断层扫描,以评估小梁和皮质密度,骨内膜和骨膜围和极应力应变指数。使用在1s时间内平均的7天腕部佩戴原始加速度数据来估计在PA强度增量(从200到3000mg的50毫重力单位(mg)增量)以上累积的时间。使用多元线性回归评估超过50mg增量的时间与骨结局之间的关联。根据年龄调整,性别,高度,体重,成熟,社会经济地位,肌肉横截面积和PA低于感兴趣的强度。随着强度从>200mg增加到>700mg,所有骨相关结局的平均R2变化逐渐增加。所有结果在>700mg时变得显著(R2变化=0.6%-1.3%,p=0.001-0.02)。强度的任何进一步增加导致平均R2变化的降低,并且对于>1500mg的所有结果,关联变得不显著。使用更合适的加速度测量方法(1-s时期;没有传统切点的先验应用)使我们能够确定PA>700mg(相当于跑步〜10km/h)的〜10分钟/天与pQCT衍生的骨密度测量呈正相关,11-12岁儿童的几何形状和力量。
    Physical activity (PA) during childhood and adolescence is important for the accrual of maximal peak bone mass. The precise dose that benefits bone remains unclear as methods commonly used to analyze PA data are unsuitable for measuring bone-relevant PA. Using improved accelerometry methods, this study identified the amount and intensity of PA most strongly associated with bone outcomes in 11-12-year-olds. Participants (n = 770; 382 boys) underwent tibial peripheral quantitative computed tomography to assess trabecular and cortical density, endosteal and periosteal circumference and polar stress-strain index. Seven-day wrist-worn raw acceleration data averaged over 1-s epochs was used to estimate time accumulated above incremental PA intensities (50 milli-gravitational unit (mg) increments from 200 to 3000 mg). Associations between time spent above each 50 mg increment and bone outcomes were assessed using multiple linear regression, adjusted for age, sex, height, weight, maturity, socioeconomic position, muscle cross-sectional area and PA below the intensity of interest. There was a gradual increase in mean R2 change across all bone-related outcomes as the intensity increased in 50 mg increments from >200 to >700 mg. All outcomes became significant at >700 mg (R2 change = 0.6%-1.3% and p = 0.001-0.02). Any further increases in intensity led to a reduction in mean R2 change and associations became non-significant for all outcomes >1500 mg. Using more appropriate accelerometry methods (1-s epochs; no a priori application of traditional cut-points) enabled us to identify that ∼10 min/day of PA >700 mg (equivalent to running ∼10 km/h) was positively associated with pQCT-derived measures of bone density, geometry and strength in 11-12-year-olds.
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  • 文章类型: Journal Article
    背景:目前的研究,深入研究了希腊样本中胫骨近端形态参数,不仅分析了特定的线性距离比率是否一致,而且为使用恒定比率进行膝关节置换术成像研究的潜在新型公制系统铺平了道路。这些发现可能对未来扩大的研究和临床实践具有重要意义。
    方法:由两名独立研究者对38只干燥的胫骨进行了评估。使用数字游标器滑动卡尺测量以下距离:(1)近端表面的中侧距离(A),(2)近端表面的前后距离(B),(3)骨的纵向长度(C),(4)连接近端表面前缘与胫骨结节最高峰的线(D),(5)内侧关节小平面(AF)(内侧平台)的近端边缘的深度(E)和(6)外侧AF(外侧平台)的近端边缘的深度(F)。
    结果:A,B,C,D,E,F的平均距离为71.3毫米,47.4mm,340.2mm,37.1mm,42mm,和35.9毫米。每个观察者对所有测量的可靠性分析显示,类间相关性(ICC)得分为0.975(观察者1)和0.971(观察者2)。比率A/B为1.5,A/C为常数0.2,D/C为0.1。E/F比为1.2。六个测量值(A-F)显示出优异的观察者间可靠性(所有ICC值>0.990)。
    结论:研究确定了胫骨近端周围线性距离的恒定比率。考虑到这些比率,膝关节置换术中的不对称胫骨组件似乎更紧密地复制了天然解剖结构。此外,从近端表面的前缘到胫骨结节峰的距离,构成胫骨纵向长度的十分之一,显示出作为成像研究的公制系统的希望,尤其是评估胫骨组件周围的病变。
    BACKGROUND: The current study, which delves into proximal tibia morphometric parameters in a Greek sample, not only analyzes whether specific linear distance ratios are consistent but also paves the way for a potential novel metric system for knee arthroplasty imaging studies using constant ratios. These findings could have significant implications for future enlarged research and clinical practice.
    METHODS: A total of 38 dried tibiae were evaluated by two independent investigators. The following distances were measured with a digital Vernier sliding caliper: (1) the mediolateral distance of the proximal surface (A), (2) the anteroposterior distance of the proximal surface (B), (3) The longitudinal length of the bone (C), (4) the line connecting the anterior margin of the proximal surface with the highest peak of the tibia tuberosity (D), (5) the depth of the proximal margin of the medial articular facet (AF) (medial plateau) (E) and (6) the depth of the proximal margin of the lateral AF (lateral plateau) (F).
    RESULTS: The A, B, C, D, E, and F mean distances were 71.3 mm, 47.4 mm, 340.2 mm, 37.1 mm, 42 mm, and 35.9 mm. Reliability analysis for each observer on all measurements revealed an interclass correlation (ICC) score of 0.975 (observer 1) and 0.971 (observer 2). The ratio A/B was 1.5, A/C was a constant 0.2, and D/C was 0.1. The ratio E/F was 1.2. The six measurements (A-F) showed excellent inter-observer reliability (all ICC values > 0.990).
    CONCLUSIONS: The study established constant ratios of the studied linear distances around the proximal tibia. Considering these ratios, asymmetrical tibial components in knee arthroplasty seem to replicate the native anatomy more closely. Furthermore, the distance from the anterior margin of the proximal surface to the tibial tuberosity peak, constituting one-tenth of the longitudinal length of the tibia, shows promise as a metric system for imaging studies, especially in assessing lesions around tibial components.
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  • 文章类型: Journal Article
    骨折被认为是导致严重并发症的医疗紧急情况。
    本研究旨在描述Ag-NPs-FG对兔骨折愈合的加速作用。
    用胡芦巴(FG)还原银NPs(AgNPs),装入淀粉凝胶基质中,并研究了它们的形态,尺寸,和收费。40只成年雄性兔随机组成4组。在每只兔的右胫骨的近端干meta处产生3.5mm直径的骨缺损。第1-4组注射安慰剂生理盐水,AgNPs-FG,普通凝胶,和骨缺损区的FG凝胶,分别。术后8周根据影像学评估愈合情况,骨转换标记,和组织病理学检查。
    获得的AgNPs-FG为淡红色,球形,吸光度为423nm,尺寸为118.0±1.7nm,和-7.8±0.518mV的表面电荷。制备的AgNPs-FG水凝胶清晰,半透明,和同质的。pH值为6.55-6.5±0.2,粘度为4,000和1,875cPs,FG和AgNPs-FG水凝胶的铺展性分别为1.6±0.14和2.0±0.15,分别。与其他治疗组相比,第2组的放射学结合量表显着改善(p<0.05),骨转换标志物显着增加(p<0.05)。组织病理学检查显示,第2组和第4组在术后第28天形成成熟骨。
    载有AgNPs-FG水凝胶的胶体纳米制剂可能是加速兔胫骨骨愈合过程的有前途的制剂。
    UNASSIGNED: A fracture is considered a medical emergency leading to considerable complications.
    UNASSIGNED: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits.
    UNASSIGNED: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1-4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations.
    UNASSIGNED: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of -7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly (p < 0.05) improved in group 2 with a significant (p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4.
    UNASSIGNED: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits\' tibial bone healing process.
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  • 文章类型: Journal Article
    目的:验证单阶段双侧与单侧内侧开放楔形胫骨高位截骨术(HTO)的安全性和临床效果。
    方法:一项倾向匹配队列研究于2020年3月至2021年3月在我们的医疗中心进行。数据是前瞻性收集的。包括34例接受单阶段双侧内侧开放HTO(SSBHTO)的患者,单侧组68例。基于年龄,倾向匹配比例为2:1,性别,和体重指数使用R软件。住院时间的比较,手术时间,失血,术后不良事件,90天再入院率,转换为TKA率,我们进行了自我报告的VAS和WOMAC评分,以调查双侧HTO的安全性和临床结果.
    结果:SSBHTO的平均住院时间为7.36±2.23天,平均住院时间为7天(IQR,3天;范围,4至23天)为单侧组(P=0.219)。双侧HTO的平均手术时间为144±47分钟,单侧OWHTO的平均手术时间为105(37.5)分钟(P<0.001)。SSBHTO的平均失血量为150(100)ml,单侧OWHTO的平均失血量为100(50)ml(P<0.001)。两组患者的不良事件和90d再入院率差异无统计学意义。随访结束时,未观察到HTO失败或转换为膝关节置换术。VAS,疼痛,刚度,术后1年,两组WOMAC量表功能评分基本具有可比性(P>0.05)。
    结论:膝关节骨性关节炎患者宜采用单阶段双侧内侧开口楔形胫骨高位截骨术。患者受益于避免二次麻醉,术后并发症,和大量的成本节约。
    方法:治疗级别III。
    OBJECTIVE: To validate the safety and clinical results of single-stage bilateral versus unilateral medial opening wedge high tibial osteotomy (HTO).
    METHODS: A propensity-matched cohort study was performed from March 2020 to March 2021 in our medical center. Data were prospectively collected. Including 34 patients who underwent single-stage bilateral medial opening HTO(SSBHTO), and 68 cases in the unilateral group. Propensity-matched ration was 2:1 based on age, sex, and body mass index using R software. Comparisons of the length of hospital stay, operative time, blood loss, postoperative adverse events, 90-day readmission rate, conversion to TKA rate, self-reported VAS and WOMAC scores were made to investigate the safety and clinical results of bilateral HTO.
    RESULTS: The mean length of hospital stay was 7.36 ± 2.23 days for SSBHTO and 7 days (IQR, 3 days; range, 4 to 23 days) for the unilateral group (P = 0.219). The mean operative time was 144 ± 47 min for bilateral HTO and 105(37.5) mins for a unilateral OWHTO (P < 0.001). The mean blood loss was 150(100) ml for SSBHTO and 100(50) ml for unilateral OWHTO (P < 0.001). There were no significant difference of the adverse events and 90-day readmission rate between two groups. No failed HTO or conversion to knee arthroplasty were observed at the end of follow-up. VAS, pain, stiffness, and functional scores of the WOMAC scale were essentially comparable of two groups one year after surgery (P > 0.05).
    CONCLUSIONS: A single-stage bilateral medial opening wedge high tibial osteotomy is advisable for patients with knee osteoarthritis. Patients benefit from avoiding secondary anesthesia, postoperative complications, and substantial cost savings.
    METHODS: Therapeutic Level III.
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  • 文章类型: Journal Article
    先天性胫骨假关节(CPT)是一种严重的病理特征是自发性骨折无法愈合,导致纤维状骨不连。一半的CPT患者受到NF1肿瘤抑制基因突变引起的多系统遗传性疾病1型神经纤维瘤病(NF1)的影响,RAS-丝裂原活化蛋白激酶(MAPK)信号通路的负调节因子。这里,我们分析了CPT和Prss56-Nf1基因敲除小鼠的患者,以阐明CPT相关的纤维骨不连的致病机制,并探索了治疗CPT的药理学方法.我们确定了病理性骨膜中NF1缺陷的雪旺氏细胞和骨骼干/祖细胞(SSPC)为驱动纤维化的受影响细胞类型。而缺乏NF1的SSPC采用了纤维化的命运,NF1缺陷的雪旺氏细胞产生关键的旁分泌因子,包括转化生长因子-β,并诱导野生型SSPC的纤维化分化。为了抵消NF1缺陷的施万细胞和SSPC中RAS-MAPK信号传导的升高,我们使用MAPK激酶(MEK)和Src同源2含蛋白酪氨酸磷酸酶2(SHP2)抑制剂。在Prss56-Nf1基因敲除小鼠模型中,体内联合抑制MEK-SHP2可预防纤维骨不连,为CPT中骨不愈合的治疗提供了一种有前途的治疗策略。
    Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the NF1 tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and Prss56-Nf1 knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified NF1-deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas NF1-deficient SSPCs adopted a fibrotic fate, NF1-deficient Schwann cells produced critical paracrine factors including transforming growth factor-β and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both NF1-deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the Prss56-Nf1 knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.
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