肝移植术后慢性排斥反应的临床与病理分析

目的 探讨原位肝移植术后慢性排斥反应的病理组织学特点、临床表现以及诊治经验.方法 回顾性分析2004年1月至2006年12月收治的516例原位肝移植患者的临床病理资料;对肝移植术后发生慢性排斥反应患者的病理组织学改变、临床表现、诊治方案加以分析.结果 516例肝移植患者中,发生慢性排斥反应12例(2.3%,12/516),其中早期慢性排斥反应7例,晚期慢性排斥反应5例.其主要组织学特征是移植肝组织内的胆管严重减少或缺失和累及中等动脉的闭塞性动脉炎;其中早期慢性排斥反应可表现为小叶间胆管的细胞变性和其数量进行性减少以及形成小叶中央坏死性炎症.12例慢性排斥反应患者中,7例早期慢性排斥反应患者经激素冲击治疗和调整免疫抑制药物后病情得到控制(包括2例接受抗CD3抗体治疗,2例接受抗胸腺细胞球蛋白治疗)且近期疗效满意;5例晚期慢性排斥反应患者肝功能迁延不愈最终至肝功能衰竭而行再次肝移植,其中2例伴术后严重腹腔内感染而死亡,1例死于术后多脏器功能衰竭,另外2例再移植病例获临床治愈.本组慢性排斥反应发生的时间为术后4～26个月;与慢性排斥相关的病死率为25.0%(3/12).结论 肝移植术后发生慢性排斥反应的患者缺乏典型的症状和体征,其病理改变可以有重叠和复合存在;移植肝连续穿刺活检和再次移植术后病理仍是目前诊断慢性排斥反应的"金标准".如能及时发现早期慢性排斥反应并积极进行合理的治疗,病情则具有潜在的可逆性;晚期阶段慢性排斥反应所致的移植肝功能衰竭需要再次肝移植治疗.     

肝移植术后严重感染状态下的严重排斥反应3例报告

回顾性分析收治的3例肝移植患者在严重感染状态下免疫抑制治疗的临床资料。结果示1例活体辅助肝移植患者几乎完全停用免疫抑制剂后发生严重排斥反应导致移植肝丧失；1例老年肝移植患者免疫抑制剂减量后出现严重排斥反应，立即予激素冲击治疗获良好效果；1例患者大幅减少免疫抑制剂后发生严重排斥反应，导致门静脉血栓形成而被迫再次肝移植。提示肝移植术后严重感染状态下行免疫抑制剂减量或停用时须密切观察是否发生急性排斥反应；一旦发生，宜果断予加强免疫抑制剂治疗。     

肝移植术后迟发型急性排斥反应的发生和治疗

目的探讨肝移植术后迟发型急性排斥反应（lateacuterejection，LAR）的发生率、处理和预后。方法回顾性分析我科2004年8月至2006年8月收治的15例迟发型急性排斥反应（肝移植术6个月后发生的急性排斥反应）患者的临床资料。结果15例LAR发生在术后6．6—27个月，平均（14．7±7．5）个月。其中男14例，女1例。年龄32～66岁，平均年龄（49．5±12．7）岁。原发疾病为重症肝炎或肝功能衰竭者8例，占53．3％（8／15）；发生于血型不合移植者2例，免疫抑制治疗方案为单一普乐可复（FK506）治疗8例，单一环孢素A（CsA）治疗3例，已经停用激素13例，占86．7％。属于免疫抑制剂量不足者共10例，占66．7％。免疫抑制剂浓度正常范围者5例。按Banff分级标准排斥反应的程度为轻度者9例，中度6例，无重度排斥反应发生。治疗方法均首先加强或调整免疫抑制治疗，包括提高药物浓度、FK506／CsA转换、联合其他免疫抑制剂和激素冲击治疗，3例患者需长期口服激素。总的治愈率为80％，3例患者逐渐出现缺血型胆道病变，其中1例行再移植后死亡。结论迟发型急性排斥反应是肝移植术后常见但预后较好的并发症之一，免疫抑制不足是其发生的主要原因，及时地加强免疫抑制治疗可逆转排斥反应。     

肝移植术后急性排异反应的早期诊断和治疗体会

目的 探讨肝移植术后急性排异反应的早期诊断和治疗.方法 回顾分析自2001年8月至2007年4月间56例同种异体原位肝移植术后急性排异反应患者诊治的临床资料.结果 7例肝移植后6~96 d出现急性排异反应,平均20 d,7例经肝穿刺活检确诊.经激素冲击及大剂量骁悉、FK506治疗,急性排异反应均得到良好控制.结论 临床观察和肝功能化验可及时提示急性排异反应的发生.诊断的最终确立依赖于肝穿活检,合理应用免疫抑制剂则是治疗的关键.     

肝移植急性排斥反应的诊断与治疗

目的 总结肝移植术后急性排斥反应(AR)的诊治经验。方法 回顾性分析57例肝移植患者术后AR的发生率和治疗结果。结果 21例患者术后因肝功能异常而行38次移植肝活检(术后6～91d)，11例15次发生AR，其中8例为单次，3例为两次或两次以上，轻度11次，中重度4次，AR发生率为19．3％(11／57)。20次为单纯保存-再灌注损伤(PRI)。3次为药物中毒。所有AR均经激素冲击或调整FK506剂量后缓解。结论 移植肝活检对于AR的诊断与鉴别诊断有重要意义，只要给予及时的诊断与治疗，AR一般是可逆的。     

肝移植急性排斥反应的诊断和治疗体会(附3例改良背驼式肝移植报告)

目的探讨肝移植术后急性排斥反应的诊断和治疗。方法2001年9月至2003年6月成功进行了3例同种异体原位肝移植术。术前诊断：1．乙肝后肝硬化．2．肝移植术后感染丙型肝炎导致移植肝无功能，3．硬化性胆管炎、肝功能衰竭。术后均采用环孢素A和甲基泼尼松龙两联免疫抑制疗法。结果3例肝移植术后共出现3次急性排斥反应。排斥反应时血清谷丙转氨酶及胆红素急剧升高。肝穿刺活检明确诊断。经过冲击治疗后．3次急性排斥反应均被控制。结论合理应用免疫抑制剂是控制急性排斥反应的关键．应用环孢素A可适当延长术后早期静脉应用时间。     

肝移植术后早期激素撤离的临床观察

目的探讨肝移植术后免疫抑制治疗方案中激素的撤离。方法58例肝移植患者,术后采用环孢素A和激素预防排斥反应,10例患者加用霉酚酸酯。术后2～3周,患者的肝功能正常,无排斥反应发生时,试行逐步撤离激素。结果术后随访(9.3±5.5)个月,存活54例,死亡4例,死亡原因为非免疫因素。存活的54例中,术后3个月的激素撤离率为72.2%(39/54),6个月时为76.2%(32/42),12个月为77.8%(21/27)。3例在激素撤离过程中出现排斥反应,恢复减量前剂量,排斥逆转后再次撤离激素;10例加用霉酚酸酯者,术后3～4个月均成功撤离激素。结论术后采用以环孢素A为基础的免疫抑制方案的肝移植患者,部分患者能安全撤离激素。     

肝移植术后患者自行停药致急性排斥反应(附3例报告)

目的探讨肝移植术后患者自行停药致急性排斥反应(AR)的临床特点及治疗。方法回顾性分析2004年1月至2013年6月上海交通大学医学院附属瑞金医院肝移植中心收治肝移植术后因自行停药导致AR的3例患者的临床资料。结果 3例患者均因自行停止服用免疫抑制剂出现肝功能异常而入院治疗,停药18～42 d,经肝穿刺组织病理学结果明确均为急性细胞性排斥反应。给予恢复使用免疫抑制剂的同时采用肾上腺皮质激素(激素)冲击治疗或兔抗人胸腺细胞免疫球蛋白治疗后改小剂量激素维持。2例患者经治疗后好转,另1例经抢救后无效死亡。结论肝移植术后自行停药易发生AR,后果严重,应加强对患者的宣传教育,提高其服药依从性。一旦发生AR,即给予恢复使用免疫抑制剂,同时采用激素冲击或抗体治疗。     

一例成功的肝移植

对１例乙型肝炎肝硬变患者实施原位肝移植术，使用ＵＷ液保存共体肝脏６小时，术中采用静脉－静脉转流。术后应用大剂量中基强的松龙和标准剂量的环孢素Ａ（ＣｓＡ）进行免疫抑制治疗，对术后迟发性急性排斥反应使用甲基强的松龙冲击治疗，根据血中ＣｓＡ浓度调整ＣｓＡ用量，术后第６个月时ＨＢｓＡｇ再度转为阳性，但目前患者一般情况良好，生活片理，肝脏功能正常。认为乙型肝炎患者施行肝移植时必须配合相应的治疗，以预防肝炎复     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为"免疫特惠器官",肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.     

Intraoperative autotransfusion is associated with modest reduction of allogeneic transfusion in prosthetic hip surgery

Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r²=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.     

缺氧对肾小管上皮细胞分泌外泌体的影响

目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    （1）常氧（21% O₂）及缺氧（1% O₂）分别处理大鼠肾小管上皮细胞（NRK-52E）48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。（2）在共培养实验中,以不同浓度（1、10、50、100、300 mg/L）的常氧外泌体、缺氧外泌体分别干预脂多糖（LPS）诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验（ELISA）法分别检测巨噬细胞白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型氮氧化物合酶（iNOS）水平;使用Western印迹法检测巨噬细胞磷酸化（p）STAT/STAT及细胞因子信号传导抑制蛋白1（SOCS1）的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA（microRNA,miR）的表达差异。 结果    （1）离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。（2）缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌（均P＜0.01）,同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达（均P＜0.01）;对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高（P＜0.05）。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。     

In Vitro Function and Durability Assessment of a Novel Polyurethane Heart Valve Prosthesis

Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy: A controlled randomised trial

Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O₂ flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg^?1· h^?1 vs. 6.6 ± 4.8 μg · kg^?1· h^?1), a lower O₂ supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO₂ was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.