【作者】 高文；

【导师】 龚剑峰；

【作者基本信息】 南京大学 ， 临床医学， 2018， 硕士

【摘要】 溃疡性结肠炎(UC)是一种由环境、基因、免疫等多种因素作用下产生的慢性肠道炎症反应,与克罗恩病(Crohn’s Disease,CD)合称为炎症性肠病(Inflammatory bowel disease,IBD)。临床主要表现为腹泻、粘液脓血便伴腹痛、里急后重及不同程度的全身症状,而根据其临床炎症程度的不同可分为轻、中、重度。其中,急性重症溃疡性结肠炎(ASUC)是溃疡性结肠炎最严重的发病状态,欧洲循证共识指南提出,ASUC的诊断标准如下:a:腹泻>=6次/天;b:心率>90次/分钟,体温>37.8℃,血红蛋白<10.5g/dl,红细胞沉降速率>30mm/h或C反应蛋白>30mg/l。满足诊断标准a并且伴有b中任何一种临床表现即可诊断ASUC。在临床上在排除相关用药禁忌症情况下,ASUC的一线治疗方案主要为激素冲击治疗。然而研究表明,有30-40%的患者会出现激素无效,出现激素无效的病人应考虑行“挽救”治疗或手术治疗,如果一味的追求激素治疗疗效而延迟手术时机,会很大程度上增加患者术后并发症发生率甚至死亡率。因此,当激素耐药发生时,应需要迅速改变治疗方案以避免患者病情的恶化。早期评估疾病严重程度,预测手术发生的风险,对于指导优化治疗策略至关重要。早期识别、评估对激素治疗无反应的患者,及时行手术治疗是影响疾病预后的关键环节。近年来,大量研究表明溃疡性结肠炎内镜严重度指数(UCEIS)和梅奥内镜评分(MES)可有效评估溃疡性结肠炎(UC)患者病情严重程度;然而,对于UCEIS与MES是否可以用来指导急性重症结肠炎患者手术治疗时机的选择缺乏相关报道。急性重症溃疡性结肠炎患者往往病情危重,目前常用的检查手段如肠镜检查,甚至会增加出血、中毒性巨结肠甚至肠穿孔的风险。此外,由于内镜操作者经验的差别,以及对于内镜下出血程度评估的主观性,使得内镜评分结果出现不同程度的偏差。然而,目前尚未有一种客观准确且简单易行的评价指标用来预测急性重症溃结手术风险。研究表明,在梗阻型小肠克罗恩病患者中,血小板活化能有效的反映肠道血管内皮细胞损害引起的肠道炎症改变,血小板与白蛋白比值>125可作为预测此类疾病需手术治疗的独立危险因素。前期研究表明,UCEIS>7分的急性重症溃结患者,手术风险较高。此类患者肠道病变较重,出血明显,患者血红蛋白含量长呈现较低水平。因此,我们致力于分析血小板与血红蛋白,这两种反映肠道炎症状态与肠道出血程度的指标,在预测急性重症溃结药物治疗失败需行手术治疗中的价值。本实验分为两部分,第一部分:评价并对比溃疡性结肠炎内镜下严重度指数(UCEIS)与梅奥内镜评分(MES)指导急性重症溃疡性结肠炎手术的临床价值;第二部分:血小板与血红蛋白比值预测急性重症溃疡性结肠炎手术风险的研究。第一部分评价并对比溃疡性结肠炎内镜严重度指数(UCEIS)与梅奥内镜评分(MES)指导急性重症溃疡性结肠炎手术的临床价值目的:通过对比溃疡性结肠炎内镜严重度指数与梅奥内镜评分对于预测急性重症溃疡性结肠炎手术风险的准确性及敏感性,选择更准确的评分标准,指导临床早期准确的识别出临床中可能出现药物治疗无效且需手术治疗的患者。方法:对2014年1月至2016年5月期间的我院收治的ASUC患者进行回顾性评估。主要观察指标包括:基线资料,既往治疗史,临床表现,实验室检查,药物治疗和内镜评估结果。主要观察终点为住院或随访期间患者因重症溃结行手术治疗。结果:研究共纳入了 92名患者。37(40.2%)需要结肠切除术。多变量分析显示:UCEIS指数对于重症溃结手术治疗有预测意义(OR,3.25;95%CI,1.77-5.97;P<0.001)。ROC曲线下面积为0.85,敏感性为60.3%,特异性为85.5%,优于MES的0.65;同时当UCEIS评分≥7时,80%的患者最终需要行手术治疗。结论:本研究发现作为ASC患者需要行结肠切除术的预测指标UCEIS优于MES。当UCEIS评分大于7分时,提示患者药物治疗失败需行手术治疗的可能性高。第二部分血小板与血红蛋白比值预测急性重症溃疡性结肠炎手术风险的研究目的:通过单因素与多因素分析,明确激素治疗无效的危险因素,验证UCEIS在ASUC中预测激素治疗结果的有效性,同时,找出血小板与血红蛋白比值和UCEIS之间的相关性,探索血小板与血红蛋白比值替代UCEIS作为预测激素治疗疗效的可能性,指导临床早期准确的识别出临床中可能出现药物治疗无效且需手术治疗的患者。方法:对2016年1月至2017年12月期间的我院收治的ASUC患者进行回顾性评估。主要观察指标包括:基线资料,既往治疗史,临床表现,实验室检查,药物治疗和内镜评估结果。主要观察终点为住院或随访期间患者因重症溃结行手术治疗。结果:研究共纳入了 99名患者。37(37.4%)需要结肠切除术。多变量分析显示:入院血小板与血红蛋白比值对于重症溃结激素治疗无效需行手术治疗有预测意义(OR,8.77;95%CI,6.13-9.98;P<0.001)。ROC 曲线下面积为 0.85,敏感性为64%,特异性为88%;同时当血小板与血红蛋白比值≥6.50时,80%的患者最终需要行手术治疗。结论:本研究发现血小板与血红蛋白比值可以用来预测急性重症溃疡性结肠炎需早期行手术治疗的危险因素。当此比值大于6.50时,提示患者药物治疗失败需行手术治疗的可能性高。更多还原

【Abstract】 Part OneTo evaluate and compare the clinical significance of Ulcerative Colitis Endoscopic Severity Index(UCEIS)and Mayo Endoscopic Score(MES)in the management of severe acute ulcerative colitisObjective:By comparing the accuracy and sensitivity of ulcerative colitis endoscopic severity index and Mayo endoscopic scoring for predicting the surgical risk of acute severe ulcerative colitis,more accurate scoring criteria were selected to guide clinical to identificate the patiens who may be failed medical treatment and need surgery.Methods:A retrospective review of ASUC patients admitted to our hospital between January 2014 and May 2016 was conducted.The main observations included:baseline data,previous treatment history,clinical manifestations,laboratory tests,medications,and endoscopic findings.The primary endpoint was surgical treatment of severe ulceration during hospitalization or follow-upResults:A total of 92 patients were included in the study.37(40.2%)required colectomy.Multivariate analysis showed that:UCEIS index had predictive significance for severe ulcer surgical treatment(OR,3.25;95%CI,1.77-5.97;P<0.001).The area under the ROC curve was 0.85,the sensitivity was 60.3%,and the specificity was 85.5%,which was better than 0.65 for MES.At the same time,when the UCEIS score was≥7,80%of patients eventually needed surgery.Conclusion:This study found that UCEIS,a predictor of colectomy for patients with ASC,is superior to MES.When the UCEIS score was greater than 7 points,it was suggested that the patient’s medical treatment failed because of the possible high surgical treatment.Part TwoThe ratio of platelet to hemoglobin:Predicting the risk of surgical in severe acute ulcerative colitisObjective:Through univariate and multivariate analysis,the risk factors for sterior therapy failure were identified,and UCEIS was validated for predicting the effectiveness of hormone therapy in ASUC.At the same time,the correlation between platelet and hemoglobin ratios and UCEIS was found.Substituting UCEIS as a predictor of the therapeutic efficacy of hormone therapy guides clinically accurate identification of patients in the clinic who may have failed drug treatment and require surgical treatment.Methods:We retrospectively evaluated ASUC patients admitted to our hospital from January 2016 to December 2017.The main observations included:baseline data,previous treatment history,clinical manifestations,laboratory tests,medications,and endoscopic findings.The primary endpoint was surgical treatment of severe ulceration during hospitalization or follow-up.Results:The studyincluded a total of 99 patients.37(37.4%)required colectomy.Multivariate analysis showed that:The ratio of platelet to hemoglobin at admission was predictive of surgical treatment for severe invasive corticosteroid therapy(OR,8.77;95%CI,6.13 to 9.98;P<0.001).The area under the ROC curve was 0.85,the sensitivity was 64%,and the specificity was 88%.At the same time,when the ratio of platelet to hemoglobin≥6.50,80%of patients eventually needed surgery.Conclusion:This study found that the platelet to hemoglobin ratio can be used to predict the risk factors for early surgical treatment of severe acute ulcerative colitis.When the ratio is greater than 6.50,it is highly probable that the patient needs medical treatment because of failure of drug treatment.更多还原