Abstract
目的
观察牙周炎病史患者种植后的中,长期临床效果,探讨软组织垂直厚度对植体周组织健康及植体周病发生的影响.
方法
根据种植术中测量的植入位点软组织垂直厚度,将66名患者的66颗植体分为正常组(normal,软组织垂直厚度 ≤4.5 mm)及过厚组(thick,软组织垂直厚度 >4.5 mm)两组.随访至少2年后进行复查,记录植体留存情况,植体周探诊深度,出血指数,菌斑指数,植体周边缘骨吸收量及植体周病发生情况,并进行统计分析,比较两组之间的差异.
结果
植体留存率为100%.复查时过厚组植体的植体周探诊深度最大值(max PDi),植体周探诊深度平均值(mean PDi),植体周出血指数最大值(max BIi),植体周出血指数平均值(mean BIi),植体近中边缘骨吸收量平均值,植体远中边缘骨吸收量平均值,植体周边缘骨吸收量平均值,植体周菌斑指数平均值(mean PLIi)均显著高于正常组(P＜0.05).此外,正常组复查时植体周炎发病率2.3%,过厚组复查时植体周炎发病率34.8%,两组植体周炎发病率的差异有统计学意义(P＜0.05).
结论
牙周炎患者种植位点的软组织垂直厚度对植体周软硬组织健康存在显著影响;过厚的软组织垂直厚度与植体周探诊深度及植体周边缘骨吸收量增多有关,最终可能增加植体周病的发病风险.
Keywords: 牙科种植体, 软组织垂直厚度, 植体边缘骨吸收, 植体周病, 植体周炎
Abstract
Objective
To observe and investigate the effect of vertical soft tissue thickness on the peri-implant tissue condition and the prevalence of peri-implant disease in patients with history of periodontitis.
Methods
Among 210 patients who showed initial interest of implant therapy, 92 patients were included in this study and received implant surgery during 2010 and 2015. Sixty-six patients with 66 implants finally came back for T2 evaluation. Prior to the implant therapy, all the patients had received periodontal treatment. During the implant placement surgery, the distance from palatal soft tissue edge to the alveolar crest, which was defined as vertical soft tissue thickness (VT), was measured after the buccal full thickness flap was elevated. According to the cut off point which was adopted from the operating characteristic curve, 66 implants within 66 patients were divided into two groups, which were called normal group (VT≤4.5 mm) and thick group (VT>4.5 mm), respectively. Information of the patient's general status, periodontal situation and implant information were recorded. After a follow-up period of 42.9 months, the parameters of peri-implant tissue and condition of peri-implant disease were recorded. Mann-Whitney U test as well as Chi-square test were used to compare the parameters between two groups. Moreover, Kaplan-Meier method was chosen to draw the event(peri-implantitis)-free survival curve.
Results
The survival rate of the implants was 100%. At the end of the follow-up examination(T2), the parameters including max PDi, mean PDi, max BIi, mean BIi, mean MBL, MBL at distal side, MBL at mesial side, mean PLIi presented significantly higher values in thick group than in normal group (P ＜ 0.05). Moreover, the prevalence of peri-implantitis and peri-implant disease(peri-implant mucositis & peri-implantitis) in thick group was respectively 34.8% and 73.9%, which was significantly higher than 2.3% and 48.8% respectively in normal group (P＜0.05). The prevalence of peri-implant mucositis did not show significant difference in the two groups. In addition, Kaplan-Meier analysis showed that there was significant difference between the event-free survivals of the two groups.
Conclusion
The vertical soft tissue thickness around implants in patients with periodontitis has a significant effect on the health of the peri-implant tissue. Excessive vertical soft tissue thickness may result in deeper peri-implant probing depth as well as more peri-implant marginal bone loss, and eventually increase the risk of peri-implant disease. The vertical remodeling of soft tissue may be a new direction to indicate the role of periodontitis in peri-implant tissue condition. Moreover, the biological mechanism of the association between soft tissue thickness and peri-implantitis risk as well as effective approaches to prevent the adverse effect of excessive soft tissue thickness on peri-implant tissue is necessary to be investigated.
Keywords: Dental implants, Vertical soft tissue thickness, Peri-implant marginal bone loss, Peri-implant disease, Peri-implantitis
大量临床研究显示牙周炎对植体长期留存和植体周炎发生存在显著影响[1,2,3],但关于牙周炎病史对植体周病的作用机制目前仍未明确.牙周炎失牙位点的软硬组织往往受到严重破坏,种植位点软组织垂直厚度是植体留存和植体周组织健康的影响因素之一.
我国是牙周炎患病大国,众多种植修复患者是因为牙周炎失牙,因此探明牙周炎病史对植体周炎的作用机制有助于早期评估牙周炎患者植体的长期预后,并及时进行干预治疗.本研究旨在探究牙周炎病史患者种植部位的软组织垂直厚度对植体中长期临床效果的影响.
1. 资料与方法
1.1. 病例选择
本前瞻性队列研究连续登记了210名于2010年至2015年在北京大学口腔医院牙周科本课题组医师处就诊的患者.所有患者均存在因牙周炎导致的牙齿丧失,并计划接受种植修复.在接受了完善的牙周系统治疗后,总计92名患者符合纳入标准.所有纳入患者的种植手术均由同一名经验丰富的牙周医生在2010年至2015年完成.本研究开始前获得北京大学口腔医院医学伦理委员会的审查批准(IRB00001052-10047),所有研究对象均签署知情同意书.
患者纳入标准:曾患有慢性或侵袭性牙周炎,并于种植手术前进行牙周系统治疗控制牙周炎;种植修复治疗口内单牙缺失,修复方式为单冠修复;具备完善的牙周检查记录;患者于2010年至2015年接受种植手术.
排除标准:患有影响种植修复的全身疾病者;具有口腔不良习惯(夜磨牙,紧咬牙等)者;妊娠期或哺乳期患者;种植手术前牙周疾病未得到控制者;患者拒绝接受种植修复者;拒绝参加研究者.
在92名符合纳入标准的患者中,最终有66名患者(71.7%)于2018年至2019年接受了随访期评估,其中3名患者(3.3%)失访,23名患者(25.0%)因为工作繁忙等原因拒绝复诊.
1.2. 牙周治疗
在种植手术开始前,所有患者均于龈上洁治后进行了详细的牙周组织检查评估,结果显示所有纳入研究的患者均患有不同程度的牙周炎.在接受了完善的牙周基础治疗(刮治+根面平整)及必要的牙周手术治疗后,行种植手术.
1.3. 种植手术及修复
使用的植体包括骨水平及软组织水平植体(Straumann®)或骨下植体(Bicon®),所有植体植入位点及手术操作均符合制造商推荐适应证及操作流程,种植包括常规种植和即刻种植,均采用单冠修复方式,植体负荷时机为植入后3~6个月.
1.4. 基线期(T1)指标
研究收集了患者全身健康状况,吸烟情况和种植术前牙周检查表.牙周检查表记录了全口临床探诊深度(probing depth, PD),出血指数(bleeding index, BI; Mazza,1981),牙齿松动度,牙龈退缩,探诊溢脓等指标.在种植手术中,翻开颊侧全厚瓣后,于种植位置测量腭侧软组织边缘到牙槽嵴顶距离,定义为软组织垂直厚度(vertical tissue thickness,VT).此外,植体植入后及负荷后的影像学资料也纳入数据库.
1.5. 随访期(T2)评估
在2018年至2019年,纳入患者被召集进行随访期复查.在T2期检查中,记录植体相关临床指标,包括:植体留存/失败情况;每个植体进行6个位点(近中颊侧,颊侧,远中颊侧,远中舌侧,舌侧,近中舌侧)的探诊,记录植体周探诊深度(peri-implant probing depth, PDi),同时记录最大探诊深度(max PDi)并计算平均探诊深度(mean PDi);每个植体进行颊舌侧的探诊,记录植体周出血指数(BIi),采用Mazza 出血指数,记录最大出血指数(max BIi)并计算平均出血指数(mean BIi);采用Mombelli (1987)的测量方法,分别记录植体颊侧,舌侧的菌斑指数(periimplant plaque index, PLIi).此外,考虑到纳入患者普遍复诊维护次数较少,因此将患者维护状况分为两类:(1)无维护:随访期间复诊维护次数为0次;(2)有维护:随访期间复诊维护次数≥1次.
所有植体在T2期再次进行标准根尖片的拍摄,并与植体负荷时的根尖片进行影像学比较.在根尖片上测量植体近中及远中肩台到种植体-牙槽骨结合界面最冠方位点的距离(DIB)并记录.将植体肩部的直径作为已知数据通过似然比计算得到负荷时及T2期实际DIB,以补偿X线片上解剖结构的放大和变形.植体周边缘骨吸收量(marginal bleeding index, MBL)=T2期实际DIB-负荷时实际DIB,分别计算植体近中MBL,远中MBL及平均MBL.所有患者的影像学测量均为同一名研究者分两次(间隔时间≥2个月)测量获得,最终取平均值.研究者自身前后校准一致率为0.81,可靠性良好.
根据2017年国际牙周病和种植体周围病分类大会对植体周炎的共识报告,本研究将植体周黏膜炎定义为黏膜色红,组织水肿,探诊出血(包括线状或滴状)和/或溢脓,探诊深度较基线水平增加或无增加,除因初期骨改建所致的牙槽嵴顶水平改变外无骨丧失;植体周炎定义为轻探出血和/或溢脓,探诊深度较前检查增加,除最初骨改建外存在骨丧失.
1.6. 统计学分析
使用SPSS 21.0(SPSS Inc.,Chicago, IL, USA),Empower(R) 软件(www.empowerstats.com,X&Y solutions,inc.BostonMA)以及R软件(http://www.R-project.org)进行分析.
选取操作特性曲线中特异性和灵敏度最高的截止点4.5 mm(ROC曲线下面积=0.875,特异性0.737,灵敏度0.889,图1)作为软组织垂直厚度的界点,根据植入位点软组织垂直厚度将纳入植体分为正常组(种植位点VT≤4.5 mm) 和过厚组(种植位点VT>4.5 mm)两组.计量数据分别采用均数±标准差,中位数(下四分位数~上四分位数)或百分比表示.正常和过厚组采用独立样本t检验(变量符合正态分布),Mann-Whitney U 检验(变量不符合正态分布)或卡方检验对患者年龄,性别,牙周疾病类型,吸烟史,植体随访时间,植体种植位置,植体类型,植骨情况,复诊维护情况等信息进行一致性检验.因为变量均不符合正态分布,两组采用Mann-Whitney U 检验对植体周组织相关指标(max PDi,mean PDi,max BIi,mean BIi,MBL,PLIi)进行比较,并采用卡方检验分析两组植体周病及植体周炎发病率的差异.采用Kaplan-Meier分析,并运用Log-rank检验绘制以发生植体周炎为结局变量的植体未患植体周炎的生存曲线.P＜0.05(双侧)认为差异具有统计学意义.
1.
决定垂直软组织厚度分界点的ROC曲线
ROC curve for determining the cut-off point of soft tissue thickness
Cut off point of vertical soft tissue thickness with highest values of specificity and sensitivity (highest AUC=0.875) is 4.5 mm. AUC, area under the curve; ROC, receiver operating characteristic.
2. 结果
最终纳入分析66名患者,其中男性27例,女性39例,患者平均(51.2±10.7)岁(22~74岁).66例中55例(83.3%)为不吸烟或已戒烟患者,11例(16.7%)为吸烟患者.共66颗植体,包括25颗Bicon®植体,16颗Straumann®骨水平植体和25颗Straumann®软组织水平植体.植体负荷后平均随访时间(42.9±16.5)个月(24~94个月), 其中15颗植体(22.7%)的随访期达5年以上.
正常组包含43例患者的43颗植体, 过厚组包含23例患者的23颗植体,两组患者的基础信息见表1.两组患者的平均年龄,性别比例,牙周疾病类型(慢性/侵袭),牙周疾病分期(Grade Ⅰ~Ⅱ/Grade Ⅲ~Ⅳ),吸烟情况,植体负荷后随访时间及植体维护情况的差异无统计学意义.两组植体的口内分布,植体类型及植骨情况见表2.过厚组植入前牙区以及上颌的植体比例较正常组更高,但只有植体上,下颌分布情况在组间差异有统计学意义(P＜0.05).正常组软组织水平植体的比例更高,过厚组骨下型植体的比例更高,两组比较差异有统计学意义(P＜0.05).两组在植骨情况方面差异无统计学意义.
1.
患者基本信息
Patients demographics
| Soft tissue thickness |
Number of patients |
Mean age/ years |
Gender, male/female |
Periodontitis, chronic/aggressive |
Periodontitis, grade Ⅰ-Ⅱ/Ⅲ-Ⅳ |
Smoking, yes/no |
Follow-up period/months |
Maintenance frequency,M1/M0 |
| Normal | 43 | 51.4±10.1 | 16/27 | 39/4 | 5/38 | 7/36 | 37(26-55) | 29/14 |
| Thick | 23 | 51.0±11.9 | 11/12 | 18/5 | 1/22 | 4/19 | 45(32-53) | 11/12 |
2.
植体信息
The characteristics of implants
| Soft tissue thickness |
Number of implants |
Anterior region |
Posterior region |
Maxilla | Mandible | Type of implants | Bone grafting, yes/no |
||
| Subcrestal implants | Bone level | Tissue level | |||||||
| * P ＜ 0.05,statistically significant difference between normal and thick group. | |||||||||
| Normal | 43 | 9(20.9%) | 34(70.1%) | 16(37.2%) | 27(62.8) | 12(27.9%) | 10(23.3%) | 21(48.8%) | 25/18 |
| Thick | 23 | 10(43.5%) | 13(56.5%) | 16(69.6%)* | 7(30.4%)* | 13(56.5%)* | 6(26.1%) | 4(17.4%)* | 14/9 |
Mean age was expressed as x±s; Follow-up period was expressed as median.
T2期复查时无植体失败,植体留存率为100%.T2期过厚组植体的植体周探诊深度最大值(max PDi),植体周探诊深度平均值(mean PDi),植体周出血指数最大值(max BIi),植体周出血指数平均值(mean BIi),植体近中边缘骨吸收量平均值,植体远中边缘骨吸收量平均值,植体周边缘骨吸收量平均值,植体周菌斑指数平均值(mean PLIi)均高于正常组,差异有统计学意义(P＜0.05,表3).复诊时(T2)正常组中有21颗植体被诊断为植体周病(48.8%),植体周黏膜炎及植体周炎受累的植体分别为20颗(46.5%)和1颗(2.3%);过厚组中有17颗植体被诊断为植体周病(73.9%),植体周黏膜炎及植体周炎受累的植体分别为9颗(39.1%)和8颗(34.8%).过厚组植体周病及植体周炎的发病率高于正常组,差异有统计学意义(P＜0.05),两组植体周黏膜炎的发病率差异无统计学意义(表4).Kaplan-Meier分析显示植体未患植体周炎的生存曲线中,过厚组生存率低于正常组,差异具有统计学意义(P＜0.05,图2).患有植体周炎的植体相关信息见表5.
3.
随访时植体周相关指标
Peri-implant parameters at the follow up examination(T2) of ≤4.5 mm and >4.5 mm groups
| Soft tissue thickness |
Max PDi/ mm |
Mean PDi/ mm |
Max BIi | Mean BIi | Mean MBL/mm | Mean PLIi | ||
| Mesial side | Distal side | Mean | ||||||
| Normal | 4(3-5) | 3(2.3-3.5) | 2(1-3) | 2(1-2.5) | 0.39(0.00-0.67) | 0.40(0.03-0.67) | 0.38(0.16-0.64) | 2(1-2) |
| Thick | 5(4-7)* | 4.8(3-5)* | 3(2-4)* | 2.5(2-4)* | 0.74(0.52-1.07)* | 0.81(0.45-1.06)* | 0.69(0.44-1.07)* | 2(2-3)* |
4.
随访时植体周黏膜炎,植体周炎及植体周病发病情况
Prevalence of peri-implant mucositis at the follow up examination(T2) of ≤4.5 mm and >4.5 mm groups
| Soft tissue thickness | Number of implants | Peri-implant mucositis | Peri-implantitis | Peri-implant disease (Peri-implant mucositis & Peri-implantitis) |
| * P ＜ 0.05,statistically significant difference between normal and thick group. | ||||
| Normal | 43 | 30(69.8%) | 1(2.3%) | 31(72.1%) |
| Thick | 23 | 13(56.5%) | 8(34.8%)* | 21(91.3%) |
2.
植体无植体周炎发生的生存曲线图
Event-free survival rate of implants Event: peri-implantitis.
5.
患植体周炎植体的相关信息
The characteristics of implants with peri-implantitis
| Soft tissue thickness | Number of implants | Position of implants | Type of implants | Bone grafting, yes/no |
| Normal | 1 | 26 | Subcrestal implant | Yes |
| Thick | 1 | 43 | Subcrestal implant | No |
| 2 | 46 | Tissue level | Yes | |
| 3 | 16 | Tissue level | Yes | |
| 4 | 25 | Subcrestal implant | Yes | |
| 5 | 12 | Bone level | Yes | |
| 6 | 11 | Subcrestal implant | Yes | |
| 7 | 11 | Subcrestal implant | Yes | |
| 8 | 15 | Bone level | Yes |
All parameters were expressed as median (Q1-Q3). * P ＜0.05,statistically significant difference between normal and thick group. PDi, peri-implant probing depth; BIi, peri-implant bleeding index; MBL, marginal bleeding index; PLIi, peri-implant plaque index.
3. 讨论
本实验探究有牙周炎病史的患者种植位点软组织垂直厚度对植体周软硬组织健康状况及植体周炎发病率的影响,发现相较正常的软组织垂直厚度(≤4.5 mm),过厚的软组织垂直厚度(>4.5 mm)可能导致更深的植体周探诊深度,以及更多的植体周边缘骨吸收,更重要的是,软组织垂直厚度过厚(>4.5 mm)的植体发生植体周病及植体周炎的风险高于正常厚度(≤4.5 mm)的植体.
本研究软组织垂直厚度的测量方法为术中翻瓣后使用牙周探针直接测量腭侧软组织厚度,与Linkevicius等[4]的测量方法相似,该方法比超声或放射影像学测量法更为直观,且牙周探诊是测量牙周和种植体周围软组织的可靠方法.
目前,种植修复治疗已经具有很高的长期留存率,成为众多牙列缺损及牙列缺失患者修复的首选方法.植体周病是与菌斑相关的发生于植体周组织的炎症性损害,包括仅累及植体周软组织的植体周黏膜炎和同时累及植体周软硬组织的植体周围炎,是临床上常见的种植体生物学并发症.随着种植修复的广泛应用,植体周病变不容忽视.Lee等[5]对1900年至2016年的相关文献进行了meta分析,发现种植病例中46.83%的患者和29.48%的植体患有植体周黏膜炎; 19.83%的患者和9.25%的植体患有植体周炎,种植位点软组织垂直厚度是植体留存和植体周组织健康的影响因素之一.
早在1996年,Berglundh等[6]的动物研究就提出植体周围需要一定厚度的软组织,以形成生物学宽度.近年来,学者们逐渐关注到植入时软组织垂直厚度对植体早期骨结合的影响,Linkevicius等[4]的1年随访研究显示,thin组(软组织垂直厚度≤2 mm)植体植入后1年平均边缘骨吸收量,近中位点为(1.61±0.24) mm,远中位点为(1.28±0.17) mm;thick组(软组织垂直厚度>2 mm)植体植入后1年平均边缘骨吸收量,近中位点为(0.26±0.08) mm,远中位点为(0.09±0.05) mm,充足的软组织垂直厚度减少了早期植体周骨吸收,两者比较差异有统计学意义(P＜0.05).后续研究进一步证实了垂直软组织较薄可能导致更多的早期植体周骨吸收[7,8,9],而通过软组织增量手术增加软组织垂直厚度能有效减少早期植体周骨丧失.有学者复习了5篇关于植体周软组织垂直厚度的短期研究(12个月)[10],meta分析显示在早期骨结合过程中,种植部位充足的软组织垂直厚度(>2 mm)有利于生物学宽度的形成,减少植体周边缘骨吸收量.关于这一发现,有一种假设认为与植体周生物学宽度的形成有关[11,12],植体周生物学宽度较天然牙生物学宽度更宽(超过2 mm),因此当植体周围软组织厚度不足时,植体周牙槽骨可能出现吸收改建以形成植体周生物学宽度.
目前,关于种植位点软组织厚度的研究均为短期研究(随访时间1年), 研究目的主要集中在探讨种植位点软组织垂直厚度对手术后早期植体周牙槽骨吸收改建的影响.而从中长期角度看,植体植入时过厚的垂直软组织是否对植体周软硬组织健康及植体周病的发生存在影响,目前尚未见相关报道.
有学者发现[13],与健康植体相比,患有植体周炎的植体周龈沟内牙周炎致病菌(如牙龈卟啉单胞菌,福赛坦氏菌)及机会致病菌(如铜绿假单胞菌和金黄色葡萄球菌)的含量更多.Papaioannou等[14]对因牙周炎失牙患者的植体进行的微生物学分析发现,植体周探诊深度与植体周沟内菌斑的致病性相关,探诊深度越深,牙周致病菌比例越大,植体患植体周炎的风险就越高.闫夏[15]对负荷后随访两年的植体的微生物分析显示,植体周探诊深度越深,植体周牙周致病菌定植的风险越高.考虑到种植位点的软组织垂直厚度与修复后植体周探诊深度关系密切,因此种植位点软组织垂直厚度对植体周组织健康的影响也应得到重视.
牙周炎是一种非常普遍的疾病,位列全球发病率最高的6种疾病之一[16].已有大量研究显示牙周炎病史是植体患植体周炎的重要风险因素之一[17,18,19,20].2017年国际牙周病和植体周病分类大会(the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions)对植体周病的影响因素进行了详细报道[1],明确指出牙周炎尤其是重度牙周炎是植体周炎的重要危险因素.相较于西方国家,我国牙周病患者病程普遍更长,牙周组织破坏程度更重.Han等[21]的多中心临床研究显示,在相同纳入标准下,中国患者的初始牙周状况更差,且随访1年后植体菌斑指数和探诊出血情况均高于西方国家纳入患者.考虑到以上问题,我国因牙周病失牙患者,拔牙前可能经历了长期的牙槽骨吸收破坏,天然牙存在深牙周袋,拔牙后软组织愈合可能导致种植位点软组织垂直厚度较厚,继而在植体周生物学宽度相对稳定的情况下形成更深的植体周沟,易于牙周致病菌的定植,导致植体周软组织炎症及边缘骨吸收,最终增加植体周病的患病风险.
需要注意的是,本研究所有纳入患者均为具有牙周病病史的患者,纳入植体的平均软组织垂直厚度为(3.8±1.4) mm.当软组织垂直厚度>4.5 mm时,植体周疾病的患病风险显著增高.Fuchigami等[22]对未患牙周炎的健康患者进行的模型和影像学测量中,种植位点平均软组织厚度与本研究相似[(3.6±1.4) mm],但该研究的垂直软组织测量时机为取模时,通过植体的工作模型进行影像学测量来分析植体周软组织垂直厚度的分布,与本研究有所不同,故结果无法比较.对于未患牙周病的健康人群,软组织垂直厚度是否对植体周组织的健康存在影响,以及软组织垂直厚度的界值设定,均需要进一步的研究探讨.
本研究正常组植体周炎发病率为2.3%,过厚组植体周炎发病率为34.8%,两组发病率差异有统计学意义,其中种植位点软组织垂直厚度>4.5 mm的植体,平均3~4年随访后植体周炎的发病率高于以往文献,Karoussis等[2]随访10年的临床研究中,有牙周炎病史的患者植体周炎发病率为 28.6%.本课题组既往研究显示[23],随访两年后,牙周炎患者的植体周炎发病率为19%,这种现象出现的原因可能为研究中绝大部分纳入患者被诊断为重度牙周炎(Grade Ⅲ or Ⅳ), 并且不同研究植体周炎诊断标准可能存在差异.
本研究为前瞻性队列研究,样本量相对较少.在以后的研究中,将延长随访时间,扩大样本量,从而进一步验证本研究的相关机制及结论.
尽管存在一定局限性,本研究仍然具有一定理论和实践意义.本研究以亚洲人群为样本,探讨种植位点软组织垂直厚度对植体周软硬组织影响,发现对于牙周炎病史患者,种植位点软组织垂直厚度对植体周组织健康及植体周病的发生存在重要的影响,过厚的软组织垂直厚度(>4.5 mm),可能导致更深的植体周探诊深度及更多的植体周边缘骨吸收,并最终增加植体周病的发病风险.
Contributor Information
孟 焕新 (Huan-xin MENG), Email: kqhxmeng@bjmu.edu.cn.
韩 劼 (Jie HAN), Email: han_jie17@sina.com.
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