肝移植术后并发症的介入治疗

目的评价肝移植术后多种并发症的介入治疗。方法回顾性的分析肝移植术后出现各种并发症并进行介入治疗的82例患者,胆管病变62例;肝动脉病变8例;下腔静脉病变13例;肝静脉狭窄7例;门静脉病变9例。胆管并发症采用经T管置入引流管、经皮肝穿刺胆管行胆汁引流或球囊扩张术。球囊扩张成形术或(和)金属支架植入术处理血管狭窄的患者;局部溶栓治疗用于术后血管内血栓形成的病例。结果在胆管并发症患者中,41例经T管置入引流管,34例行经皮穿刺胆汁引流(PTBD),球囊扩张胆道成形术9例。3例肝动脉狭窄的患者接受了球囊扩张成形术或支架植入术,1例肝动脉形成血栓者行插管溶栓,效果良好。9例下腔静脉狭窄患者行支架植入术,1例接受了球囊扩张成形术。5例肝静脉狭窄患者接受了球囊扩张成形术或支架治疗。门静脉狭窄患者中6例接受支架治疗,1例门脉血栓形成行局部溶栓,治疗不满意。结论介入治疗是处理肝移植术后胆管和血管并发症不可或缺的临床治疗方法。     

血管内支架成形术治疗基底动脉狭窄

目的 探讨血管内支架成形术治疗基底动脉狭窄的近期疗效。方法 20例症状性基底动脉狭窄应用球囊膨胀支架行血管内成形术治疗。结果 12例基底动脉恢复正常管径，8例狭窄程度减小80％以上，无手术相关并发症。无短暂性脑缺血发作(Transient ischemic sttack，TIA)或卒中再发作。脑血管造影随访13例，均无血管再狭窄。结论 血管内支架成形术治疗基底动脉狭窄的近期疗效令人满意。     

球囊扩张Apollo支架植入术治疗症状性基底动脉狭窄

目的观察球囊扩张支架植入术治疗症状性基底动脉狭窄的疗效及安全性。方法应用Apollo支架治疗18例症状性基底动脉严重狭窄（〉70%）患者,术后平均随访11个月,以改良Rankin量表（mRS）评分为基础评价治疗效果。结果对所有患者均成功植入支架,16例患者临床症状得到不同程度改善;18例中,14例mRS评分≤2分,4例mRS评分〉2分。结论球囊扩张支架植入术治疗症状性基底动脉狭窄安全、有效。     

症状性大脑中动脉狭窄的血管内干预治疗

目的 探讨经皮腔内血管成形术及血管成形支架置入术治疗症状性大脑中动脉狭窄的可行性、安全性及有效性.方法 回顾性分析39例患者经药物治疗无效、反复短暂性脑缺血发作(TIA)或有明显脑缺血症状的大脑中动脉狭窄,经皮腔内血管成形或支架置入术的治疗及术后随访结果.结果 39例大脑中动脉狭窄(左侧23例,右侧13例,双侧3例,合并颈动脉狭窄5例)患者经皮腔内血管成形术9例、血管成形支架置入术30例(术后残余狭窄程度均<10%)均获成功,术后给予抗血小板聚集治疗,临床脑缺血症状和体征明显改善.2例患者术中见对比剂外泄,但无明显临床症状,且恢复良好;1例在术后1 h出现意识变化、对侧肢体活动障碍,CT提示支架侧底节区脑出血,经手术治疗后患者遗留语言障碍及右侧肢体不全偏瘫.其余患者无并发症发生.临床随访5～60个月,仅1例在支架置入7个月后右上肢无力症状复发,但较前轻微.经颅多普勒复查26例,显示原病变侧大脑中动脉血流速度增快2例;行数字减影血管造影复查14例,2例支架内发生再狭窄,均行药物治疗观察.结论 经皮腔内血管成形术及血管成形支架置入术治疗大脑中动脉狭窄是可行、安全、有效的;大样本的长期疗效有待于进一步观察.     

血管内介入治疗肝移植术后门静脉狭窄或闭塞:5例报告

目的 观察血管内介入治疗肝移植术后门静脉狭窄或闭塞的效果。方法 对肝移植后3例门静脉狭窄及2例闭塞患者行血管内介入治疗,观察治疗效果。结果 对3例门静脉狭窄、1例门静脉闭塞行球囊扩张及支架植入术,术后造影示狭窄消失,血流通畅;对1例门静脉闭塞行球囊扩张并置管溶栓术,术后3天造影示门静脉通畅,血栓减少。1例术中发生肋间动脉出血,未见门静脉治疗相关并发症。术后4例症状逐渐消失、肝功能逐步恢复,随访期间门静脉通畅,1例支架内见少许附壁血栓;1例术后胆总管狭窄,植入胆道支架后,因重症肺炎、急性呼吸窘迫综合征、脓毒性休克死亡。结论 血管内介入治疗肝移植术后门静脉狭窄或闭塞效果良好;对移植后急性血栓形成可行球囊扩张术联合置管溶栓。     

肠系膜上动脉狭窄的血管腔内治疗

目的探讨介入治疗肠系膜上动脉狭窄的安全性及临床疗效。方法对12例肠系膜上动脉狭窄的患者行选择性肠系膜上动脉造影,然后行球囊扩张或支架植入治疗,评价疗效。结果 12例肠系膜上动脉狭窄的患者技术成功率100%,其中单纯球囊扩张2例,球囊扩张+内支架植入术10例。对所有患者随访6~24个月,平均16个月,其中10例无明显症状,2例有腹痛症状,经再次腔内治疗,症状得到明显改善。随访中所有患者均未出现肠坏死、死亡等严重并发症。结论血管腔内介入治疗肠系膜上动脉狭窄是一种安全、有效的方法。     

肝移植术后肝动脉狭窄的内支架治疗

目的 对内支架植入术治疗肝移植术后肝动脉狭窄的价值进行初步的探讨。方法 对34例肝移植发生肝动脉狭窄、闭塞患者行球囊扩张治疗，其中5例患者接受内支架植入治疗，3例为球囊扩张治疗无效患者，1例为球囊扩张后出现肝动脉内膜撕裂，另1例为肝动脉狭窄伴吻合口破裂出血。结果 5例患者均成功进行了内支架植入治疗，其中1例肝动脉狭窄伴吻合口破裂出血的患者植入支架后24h内发生支架内急性血栓形成，经手术行肝动脉重建治疗，其余4例术后治疗效果良好。结论 介入方法治疗肝移植术后肝动脉狭窄具有微创、安全、有效的优势，对于球囊扩张治疗无效或合并吻合口破裂出血的病例，可采用内支架植入治疗。     

颈动脉支架植入术并发症分析

目的 总结颈动脉球囊扩张及支架植入术(carotid artery stenting,CAS)治疗颈动脉狭窄术后并发症及处理措施.方法 回顾性分析2006年7月至2012年1月因颈动脉狭窄而接受颈动脉球囊扩张及支架植入术(carotid artery stenting)72例患者的临床资料.CAS操作采取标准治疗方法,患者术前5d均口服阿司匹林100 mg与氯吡格雷75 mg,所有患者均先放置远端保护装置,90％以上狭窄患者进行前扩张,残留狭窄＞30％则进行后扩张.结果 72例患者成功地植入颈动脉自膨式支架80枚,全部使用远端脑保护装置,5例患者行同期手术,其中冠状动脉搭桥手术( off-pumpcoronary artery bypass grafting,OPCABG)2例,左锁骨下动脉支架植入2例,1例肾动脉支架植入.住院期间并发症的发生率为37.5％(27例),其中严重并发症(死亡/卒中/心肌梗死)发生率为1.39％(1例同侧小卒中);其他神经系统并发症包括2例同侧TIA(2.78％),1例高灌注综合征(1.39％),血液动力学不稳定并发症的发生率为29.2％(21例),其中1例高血压(1.39％),5例心动过缓(8.33％),15例术后低血压(20.8％),其他2例出现穿刺点血肿(2.78％).结论 血液动力学改变(低血压、心动过缓)是CAS围手术期主要并发症,神经系统并发症发生率较低,严重并发症少见.     

27例多发性大动脉炎血管介入治疗

目的探讨血管介入治疗多发性大动脉炎(Takayasu arteritis,TA)所致血管狭窄或闭塞性病变的临床疗效。方法 2003年6月～2011年6月对27例TA经股动脉穿刺选择性血管造影,确定病变部位,明确诊断,并对因大动脉炎引起的锁骨下动脉、颈动脉、肾动脉、腹主动脉病变进行了选择性球囊扩张或支架植入手术。结果 27例施行血管腔内扩张成形术或支架植入术,其中颈总动脉扩张10例,支架2例;锁骨下动脉扩张6例;腹主动脉扩张4例;肾动脉扩张10例,支架4例;无名动脉扩张1例,支架1例;共置入支架7枚。2例颈动脉扩张时因并发症而终止治疗,其余病例病变血管均获得满意的治疗。27例随访5个月～7年,平均4年,其中<12个月6例,1～3年12例,3～5年6例,>5年3例:11例头晕、视觉异常等脑缺血症状改善;12例肾动脉狭窄所致高血压经球囊扩张及支架植入后血压控制正常;2例肾动脉狭窄在球囊扩张后14、18个月再次发生血压增高,造影显示扩张后肾动脉再次狭窄,再次行肾动脉球囊扩张成形术,扩张后高血压恢复正常。结论介入性血管内成形术治疗TA所致血管狭窄或闭塞性病变疗效满意。     

髂动脉支架联合球囊扩张血管成形术与人工血管转流术治疗下肢动脉硬化闭塞症的临床比较

目的:探讨分析球囊扩张血管成形术后置入髂动脉支架与人工血管转流术治疗下肢动脉硬化闭塞症的临床疗效.方法:收集下肢动脉硬化闭塞症68例患者(80条患肢)的临床资料,其中30例患者应用球囊扩张血管成形术后置入髂动脉支架治疗,38例应用人工血管转流术治疗,分析两组患者的近期临床症状的改善、疗效等级、并发症的发生等情况.结果:两组患者术后近期自觉症状均明显缓解,髂动脉支架联合球囊扩张血管成形组(总体有效率为81.58％)的自觉症状改善比人工血管转流术(总体有效率为69.05％)更明显,有效率无统计学差异(P＞0.05),但是前者的疗效等级略优于人工血管转流术组.结论:两种治疗方式治疗下肢动脉闭塞症均可明显缓解患者的自觉症状;如果患者的自身条件允许,可优先考虑析髂动脉支架联合球囊扩张血管成形术进行治疗.     

症状性椎基底动脉狭窄经皮腔内支架成形的初步研究

目的探讨经皮腔内支架成形治疗椎基底动脉狭窄的临床疗效及适应证。方法2004年4月-2006年12月共收治22例患者：优势侧椎动脉狭窄4例；双侧椎动脉狭窄3例；一侧椎动脉狭窄、对侧椎动脉闭塞8例；单纯基底动脉狭窄5例；优势或“孤立”椎动脉狭窄合并基底动脉串联病变2例。治疗的24处病变：椎动脉开口8例，V4段椎动脉9例，基底动脉7例；Mori A型病变16例，B型病变8例。结果22例患者技术成功率95％，术前平均狭窄率为78．3％，术后残余狭窄率平均15％（P〈0．01）。除1例基底动脉支架成形致血管破裂出血死亡，余病例在围手术期内未发生严重并发症。17例患者随访1～24个月（平均13．5个月），Malek评分为1分者12例，2分者4例，3分者1例。结论症状性椎基动脉狭窄支架成形术疗效确切，但手术的难度和风险仍较大，临床就其适应证和长期疗效需要进一步积累经验。     

右侧肱动脉入路左颈动脉支架成形术治疗颈内动脉狭窄合并牛型主动脉弓1例报告

2013年10月我科收治1例63岁女性左颈动脉狭窄,有左侧脑梗死病史并频繁出现一过性脑缺血发作（transient ischemic attack,TIA）。术前CTA检查为牛型主动脉弓,左侧颈内动脉起始部重度狭窄,但位于C2水平不适合行颈动脉内膜切除术。采用全麻下经右侧肱动脉人路穿刺,造影导管选人左颈外动脉,加硬导丝引导F6长鞘选人左颈总动脉建立手术通路,然后常规进行保护伞下的颈动脉球囊扩张和支架成形术。手术成功,未发生任何并发症。术后1个月随访,TIA症状完全消失,颈动脉超声提示左颈内动脉支架术后血流通畅。我们认为经右侧肱动脉人路行支架成形术治疗牛型主动脉弓变异的左侧颈内动脉狭窄是安全、可行的。     

Cutting balloon angioplasty in hemodialysis arteriovenous fistula stenosis resistant to conventional balloon angioplasty

Objective To investigate the efficacy and safety of cutting balloon angioplasty for the treatment of hemodialysis arteriovenous fistula stenosis resistant to conventional percutaneous transluminal angioplasty (PTA). Methods The patients with arteriovenous fistula stenosis who had suboptimal results (residual stenosis ＞30%) by conventional PTA from December 2011 to February 2015 were enrolled. All the patients received cutting balloon angioplasty were rechecked every three months. Results A total of 25 patients with age of (60.7±12.9) years had suboptimal PTA results. Eleven patients with native arteriovenous fistula (AVF) and 14 patients with graft fistula (AVG) underwent cutting PTA for 30 times. The technical success rate was 86.7% and clinical success rate was 100%. The diameter stenosis pre-procedural and post-procedural of cutting PTA was (1.7±0.6) mm and (4.5±0.8) mm respectively (P＜0.05). Six patients had multiple lesions and the stenosis consisted of 21 outflow venous, 6 graft-to-vein anastomosis, 6 cephalic arch, 2 artery and 1 puncture hole stenosis. The primary access patency at 3 and 6 months for AVF group were 70.0% and 10.0%, while for AVG group the figures were 64.3% and 7.1% (P＞0.05). The secondary access patency at 3 and 6 months for AVF group were 70.0% and 30.0%, while for AVG group the figures were 85.7% and 64.3% (P＞0.05). The follow-up time was (8.1±7.3) months. The restenosis rate was 64.0%. Cutting PTA failed to achieve technical success for four times, of whom 2 patients required graft stent implantation and 2 patients required ultra-high-pressure balloons angioplasty to finally achieve technical success. The median survival time of fistula was 173 days. Conclusions Cutting balloon angioplasty have well short-term patency and safety in arteriovenous fistula stenosis resistant to conventional PTA, especially for calcified lesion or "balloon waist". Although it could provide a satisfied long patency by recurrent PTA, the use of cutting balloon would be not advocated as the first-line treatment for fistula stenosis. The efficacy superiority of cutting balloon between AVF and AVG, as well as the cost-effect comparison between cutting balloon and high-pressure balloon, remains unclear, the verification of which requires large-sampled, prospective and randomized studies.     

支架成形术治疗颅外椎动脉硬化狭窄

目的 评价血管内支架成形术治疗颅外椎动脉狭窄的安全性及有效性.方法 回顾性分析2006年4月至2010年3月施行血管内支架成形术治疗的24例颅外椎动脉狭窄病例.MoriA型21例,Mori B型3例.动脉狭窄率60%～95%,平均狭窄率79%±10%.结果 24例共置入球囊扩张式支架24枚.技术成功率100%.术后平均狭窄率下降至4%±6%.随访3～36个月,平均随访22个月.17例有症状病例中,术后15例症状消失.1例治疗部位再狭窄伴短暂性脑缺血发作.1例术前检查提示多发梗死伴随共济失调、发作性眩晕患者,术后症状无明显改善,但无进一步脑卒中发作.彩色多普勒超声复查显示:治疗部位狭窄率＞50%5例,再狭窄发生率20.8%.按Malek评分法评定,1分22例,2分1例,4分1例.结论 应用血管内支架成形术治疗颅外椎动脉狭窄是安全、有效的.通过技术改进可以在一定程度上降低再狭窄率.

Abstract：

Objectives To evaluate the safety and efficacy of endovascular angioplasty for extracranial vertebral artery ( VA ) stenosis caused by atherosclerosis. Methods We analyzed retrospectively data of the 24 patients with extracranial vertebral artery stenosis who had been placed endovascular angioplasty from April 2006 to March 2010. According to Mori classification, there were 21 type A and 3 type B among all cases.The artery stenosis rate was 60％ -95％ , the average was 79％ ± 10％. Results Twenty-four balloon mounted stents were placed, the successful rate was 100％. Postoperatively the stenosis rate decreased to 4％ ± 6％. Patients were followed up from 3 to 36 months, the average was 22 months. Symptomes disappeared in 15 out of 17 patients. Postoperative restenosis on the treatment site with transient brain ischemia occurred in one patient. The symptoms in another patient of multiple cerebral infarction with ataxia and episodic vertigo were not relieved, although the patient didn't suffer from apoplectic seizure after the intervention. Postoperative color Doppler ultrasound revealed an over 50％ residual stenosis in 5 patients. The postoperative restenosis rate was 20. 8％. According to Malek scoring, 22 patients were scored 1 point, 1 patient scored 2 and one scored 4. Conclusions Endovascular angioplasty with stent placement is a safe and effective treatment. The restenosis rate could be futher reduced by technology improvement.     

球囊扩张联合覆膜支架植入治疗人造血管动静脉内瘘狭窄

目的 探讨球囊扩张联合覆膜支架植入治疗人造血管动静脉内瘘(AVG)狭窄的临床疗效.方法 前瞻性选取15例经皮腔内血管成型术(PTA)疗效欠佳的AVG狭窄患者,且具备以下特点:狭窄长度不超过7 cm,狭窄程度大于50％;PTA后3个月内狭窄复发2次或以上;扩张后残余狭窄＞30％或狭窄部位立即弹性回缩.所有患者在数字减影血管造影(DSA)下行球囊扩张后植入不同内径的聚四氟乙烯覆膜支架.结果 男3例,女12例,平均年龄(66±12)岁.支架植入前内瘘平均使用时间为(19.5±15.0)个月.共植入支架16枚,技术成功率100％,植入部位为静脉吻合口9例(9/15);静脉流出道6例(6/15),其中头静脉3例,肱静脉2例,腋静脉1例.首次开通率3个月为40％,6个月为19％,12个月为13％.再次开通率3个月为93％,6个月为88％,12个月为87％.术后平均随访时间为(14.9±5.3)个月,再窄狭率为87％(13/15).术后PTA 36例次,支架内狭窄36％ (13/36);支架远端狭窄8％ (3/36);支架近端狭窄22％(8/36);与支架无关的狭窄33％ (12/36).AVG中位生存时间为25个月.结论 球囊扩张联合覆膜支架植入治疗AVG狭窄技术成功率高,并发症少,首次开通率不高,但再次开通率令人满意.     

Simultaneous fenestration with stent implantation for acute limb ischemia due to type B acute aortic dissection complicated with both static and dynamic obstructions

Stanford type B acute aortic dissection is sometimes complicated with compressed true lumen of the descending aorta (Dynamic obstruction) and stenosis of a major aortic branch (Static obstruction), which cause organ malperfusion. In such a case, medical therapy alone is usually not effective and endovascular treatments are required including stent implantation and balloon fenestration. However, it is difficult to determine which strategy should be selected, that is, only stent implantation at dissected branch or simultaneous fenestration with stent implantation. We report a case of a 54-year-old man with lower leg ischemia due to type B aortic dissection, who was successfully treated with stent implantation plus balloon fenestration. This case suggests that balloon fenestration plus stent implantation should be considered when static obstruction in the aortic branches is accompanied by dynamic obstruction in the descending aorta.     

Two cases of percutaneous transluminal angioplasty (PTA) for the treatment of subclavian steal syndrome

Recently percutaneous transluminal angioplasty (PTA) has been used to treat atherosclerotic lesion of the brachiocephalic arteries. We treated two patients with subclavian steal syndrome successfully by PTA. The first patient was a 52-year-old man complaining of vertigo and ischemic symptoms of the left arm. Blood pressure was 110/90 mmHg in the left arm and 140/92 mmHg in the right. On the angiogram, about 80% stenosis was found in the proximal portion of the left subclavian artery, and retrograde filling of the left vertebral artery was observed. At first, a carotid-subclavian bypass surgery was performed, but unfortunately failed because of obstruction of the artificial arterial graft. Then we performed PTA using Grüntzig balloon dilatation catheter. The dilatation was carried out successfully. Immediately after PTA, to-and-fro and antegrade flow of the vertebral artery was observed, and one month later it became normal flow. Neurological symptoms gradually disappeared within two months. The second patient was a 57-year-old man suffering from vertigo on effort and TIA. Blood pressure was 130/78 mmHg in the left arm, and 152/82 mmHg in the right. Angiogram showed more than 95% stenosis of the left subclavian artery, and retrograde filling of the left vertebral artery. We also observed bilateral severe stenosis of the MCA. Carotid-subclavian bypass was dangerous because of the low perfusion of the ipsilateral MCA area. PTA was performed as the first choice, and the dilatation of the stenosis was sufficient. In two months natural antegrade filling of the left vertebral artery was obtained. We followed these patients for 12 months and no restenosis was observed neurologically and radiologically. We performed PTA with the Grüntzig balloon catheter using the Seldinger's method through the right femoral artery. Diameter of the balloon was 6 mm and its length was 4 cm. After setting the balloon to the stenotic lesion, we inflated the balloon with 5atm (75 psi) pressure for 30 minutes. Monitoring the blood pressure and arterial pressure wave at the tip of the catheter, we repeated inflation of the balloon 4 times. We used continuous venous infusion of low molecular dextran and heparin during PTA procedures. No complication occurred and neurological symptoms disappeared gradually. PTA is a safe and effective method, so it should be the first choice in the treatment of subclavian steal syndrome caused by severe stenosis of the subclavian artery.     

经皮腔支架植入血管成形术治疗髂动脉硬化闭塞症

目的:探讨髂动脉硬化闭塞症介入治疗.方法:应用Seldinger技术,经皮腔作髂动脉狭窄部位球囊扩张,金属支架植入血管成形术12例,结果:全部病例随访6-35个月,平均12.4个月,疗效满意,都已恢复正常活动,无痛行走的距离较术前明显增加,踝/肱指数从术前平均0.34上至0.81.结论:支架植入血管术是治疗髂动脉硬化闭塞症安全有效的方法.动脉造影是选择支架口径和长度的先决条件和重要依据.     

Should we still perform angioplasty and stenting of an unprotected left main coronary artery stenosis in heart transplant patients? Two new cases and a review of the literature.

Coronary balloon angioplasty with stent implantation has emerged as a possible alternative to bypass grafting or repeat transplantation in left main coronary stenosis in heart transplant patients. We report 2 new cases of stent implantation for unprotected and isolated left main stenosis in heart transplant patients. Despite an initially successful procedure, restenosis prompted the performance of bypass surgery in both patients. The relative advantages and disadvantages of available techniques of revascularization are discussed in the context of the literature.     

Early outcome of "cutting" balloon angioplasty for infrainguinal vein graft stenosis

BACKGROUND: Recurrent stenotic lesions associated with vein graft bypass grafts are often fibrous and smooth. Unlike de novo atherosclerotic lesions, they respond poorly to balloon angioplasty, and may often result in a dissection requiring stent placement to avoid early recurrent thrombosis or open repair of residual stenosis. A novel balloon designed with three or four longitudinally placed 0.127-mm atherotomes was used at angioplasty to treat focal peripheral vein graft stenosis, in an attempt to minimize dissection by producing a controlled plaque fracture. METHODS: Over 11 months, patients with focal (<2 cm) peripheral vein graft stenosis underwent cutting balloon angioplasty (Boston Scientific, San Diego, Calif) at two separate centers. Baseline patient demographic data, type of bypass, velocity at pre-procedural and post-procedural duplex scanning, procedural results, complications, and type of long-term anticoagulation were recorded. Follow-up consisted of duplex ultrasound scanning at 1, 3, and 6 months and every 6 months for 2 years. RESULTS: The mean age of the patients was 66.8 +/- 10 years. No intent to treat failure was noted. In most patients a 4-mm balloon was used (15 of 19) to treat 10 above-knee vein bypass grafts and 9 below-knee vein bypass grafts. No patient required placement of a stent or conversion to open surgery because of recoil, dissection, or suboptimal angioplasty. The mean velocity at pre-procedure duplex scanning at the site of vein graft stenosis was 373 +/- 56.8 cm/s, and the mean velocity post-treatment at 1-month follow-up was 144 +/- 50 cm/s. The mean length of stay was 26 +/- 32 hours. Overall, four patients continued to receive warfarin anticoagulation therapy, in addition to aspirin. During a mean follow-up of 11.4 +/- 7 months, recurrent stenosis developed in one patient. No other complications or graft recurrent thrombosis was noted. CONCLUSION: Cutting balloon angioplasty may help overcome hoop stress early, by producing a controlled, longitudinal neointimal lesion laceration and thereby facilitating a fracture line along predetermined microincisions. Our study results demonstrate acceptable early outcomes, with no requirement for bail-out stenting or open surgery.