本文關(guān)鍵詞： 創(chuàng)面 負(fù)壓創(chuàng)面療法 骶髂關(guān)節(jié)結(jié)核 脊柱結(jié)核 個(gè)體化治療　出處：《中國(guó)人民解放軍醫(yī)學(xué)院》2016年博士論文　論文類型：學(xué)位論文

【摘要】：研究背景結(jié)核性創(chuàng)面是肺外結(jié)核常見(jiàn)并發(fā)癥,呈口小底大的特征,常通過(guò)錯(cuò)綜復(fù)雜的竇道通道網(wǎng)與原發(fā)病灶膿腔相連,因此表面可見(jiàn)的結(jié)核性創(chuàng)面僅僅是病變的冰山一角。而深層結(jié)核性創(chuàng)面尤其難治,多以骶髂關(guān)節(jié)結(jié)核、脊柱結(jié)核為原發(fā)灶,本研究針對(duì)深層結(jié)核懷創(chuàng)面進(jìn)行探索。傳統(tǒng)治療方法總以保守治療為主,療程長(zhǎng)效果差,往往遷延不愈,最終仍需皮瓣移植或肌皮瓣移植閉合創(chuàng)面。近年來(lái)隨著負(fù)壓創(chuàng)面療法(Negative pressure wound therapy, NPWT)的興起,有少數(shù)研究者探索應(yīng)用NPWT臺(tái)療結(jié)核性創(chuàng)面,但僅限于小樣本病例系列研究,其作用機(jī)制也不明了。本研究擬通過(guò)NPWT臺(tái)療骶髂關(guān)節(jié)結(jié)核創(chuàng)面的自身前后對(duì)照研究明確NPWT對(duì)深層結(jié)核創(chuàng)面的有效性和機(jī)制、通過(guò)NPWT治療復(fù)治脊柱結(jié)核伴創(chuàng)面的免疫相關(guān)性研究明確復(fù)治深層結(jié)核創(chuàng)面的免疫系統(tǒng)狀態(tài)及療效評(píng)價(jià)指標(biāo)、通過(guò)探索基于SMU分型及sIL-2R的脊柱結(jié)核創(chuàng)面診療策略明確脊柱結(jié)核深層創(chuàng)面的標(biāo)準(zhǔn)化個(gè)體化診療流程目的1.探討NPWT臺(tái)療骶髂關(guān)節(jié)結(jié)核創(chuàng)面的有效性和相關(guān)機(jī)制;2.探討NPWT治療復(fù)治脊柱結(jié)核伴創(chuàng)面的過(guò)程中免疫系統(tǒng)狀態(tài)及免疫因子動(dòng)態(tài)變化情況,篩選可以準(zhǔn)確判斷病情變化的相關(guān)指標(biāo)；3.探討基于SMU分型及sIL-2R等指標(biāo)的脊柱結(jié)核創(chuàng)面?zhèn)�體化診療策略方法1.對(duì)骶髂關(guān)節(jié)結(jié)核合并慢性難治性竇道的患者進(jìn)行回顧性自身前后對(duì)照研究,收集患者一般情況資料,每例患者都經(jīng)過(guò)對(duì)照期、中間期、干預(yù)期的治療。為評(píng)估NPWT的有效性并探討其機(jī)制,比較對(duì)照期和干預(yù)期ESR、Hs-CRP、創(chuàng)面體積、引流量、微血管密度、膠原容積比等。2.上部分實(shí)驗(yàn)證實(shí)NPWT對(duì)深層結(jié)核創(chuàng)面的有效性后,將NPWT治愈的復(fù)治脊柱結(jié)核伴創(chuàng)面患者納入治療組,并選擇初治脊柱結(jié)核患者、健康成年人為對(duì)照組。將不同時(shí)間點(diǎn)定義為T0、T1、T3時(shí)相點(diǎn),在TO時(shí)相點(diǎn)比較三組T細(xì)胞亞群、ESR、 Hs-CRP值,比較三組患者外周血TNF-α、IL-2、IFN-γ、IL-12、IL-4、IL-6、IL-10、sIL-2R等。將A組TO、T1、T3點(diǎn)的Hs-CRP、IFN-γ、sIL-2R與各組相應(yīng)時(shí)相點(diǎn)BM1做線性相關(guān)分析,并將A組T1點(diǎn)Hs-CRP、IFN-γ、sIL-2R較T0點(diǎn)變化值與A組T1點(diǎn)創(chuàng)面引流量、VAS評(píng)分、脊柱病變體積較TO點(diǎn)變化值做線性相關(guān)分析。3.將脊柱結(jié)核伴創(chuàng)面患者按SMU分型及初復(fù)治情況分為A、B、C、D四組,并按個(gè)體化診療策略進(jìn)行治療,初治患者監(jiān)測(cè)ESR、Hs-CRP,復(fù)治患者監(jiān)測(cè)Hs-CRP、 sIL-2R,并根據(jù)各指標(biāo)決定NPWT療程、是否需要徹底病灶清除術(shù)、關(guān)閉創(chuàng)面的時(shí)機(jī),收集一般資料并進(jìn)行隨訪。結(jié)果1.患者形成竇道的時(shí)間為3-6月(平均3.92±1.08月),接受NPWT臺(tái)療14-35天(平均18.33±6.97),竇道封閉為NPWT之后20-42天(平均25.25+7.23)NPWT治療后創(chuàng)面組織CD34免疫組化染色顯示雖然創(chuàng)面新生微血管數(shù)量較治療前各時(shí)期變化不大,但功能性更強(qiáng),療效優(yōu)于普通換藥;NPWT治療后創(chuàng)面膠原容積比顯著高于治療前各時(shí)期(P0.001),療效優(yōu)于普通換藥。在干預(yù)期,每日引流量在頭三天由22.33±7.28m1增加至29.17±16.63ml,然后由29.17±16.63m1降至第35天的0.25±0.87m1;創(chuàng)面體積由平均34.08±33.91cm3降至25.50±26.04cm3(P0.05),經(jīng)過(guò)治療創(chuàng)面體積減少了26.98%;ESR由38.33±20.82顯著降低至25.50±11.72 mm/h (P0.05);Hs-CRP由33.67±11.72顯著降低至13.00±8.01 mg/dl(P0.05)。干預(yù)期創(chuàng)面體積、ESR、Hs-CRP較對(duì)照期明顯降低(P0.05)。2.在T0時(shí)相點(diǎn)A組ESR較C組無(wú)明顯差異,A組ESR較B組明顯降低(P0.05)；A組Hs-CRP較B組明顯降低(P0.05),雖然A組Hs-CRP接近正常值,但A組Hs-CRP較C組仍然存在明顯差異(P0.05)。在T0時(shí)相點(diǎn)B組較C組患者CD8顯著升高(P0.001),B組較C組CD4無(wú)顯著變化,B組較C組患者CD4/CD8顯著降低(P0.05)；A組較B組患者CD4比例顯著降低(P0.001),A組較B組患者CD8比例無(wú)顯著變化,A組較B組CD4/CD8顯著降低(P0.05)；A組較C組患者CD8比例顯著升高(P0.001),A組較C組患者CD4比例顯著降低(P0.01),A組較C組患者CD4/CD8顯著降低(P0.01)。A組較C組患者sIL-2R、IFN-γ有顯著升高(P0.05),A組患者1L-6較C組顯著降低(P0.05)。A組患者在TO點(diǎn)時(shí),sIL-2R、IFN-γ、HS-CRP均與BMI呈負(fù)相關(guān)(P0.05)；在T1點(diǎn)時(shí)sIL-2R、HS-CRP均與BMI呈負(fù)相關(guān)(P0.05);在T3點(diǎn)時(shí)只有sIL-2R與BMI呈負(fù)相關(guān)(P0.05)。HS-CRPT1-HS-CRPT0與治療前后創(chuàng)面引流量變化值DVT1-DVT0呈正相關(guān)(P0.05), HS-CRP T1-HS-CRPT0與治療前后脊柱疼痛變化值VAST1-VAST0呈正相關(guān)(P0.05), sIL-2RT1-sIL-2RT0與治療前后脊柱疼痛變化值VAST1-VAST0呈正相關(guān)(P0.001)3.根據(jù)SMU分型,A組初治SMU Ⅰ、Ⅱ型1例：B組復(fù)治SMU Ⅰ、Ⅱ、Ⅲa型17例,其中4例在院外經(jīng)化療藥物調(diào)整及換藥處理創(chuàng)面自行愈合,13例入院治療;C組初治SMUⅢ、Ⅳ、Ⅴ型2例;D組復(fù)治SMUⅢb、Ⅲc、Ⅳ、Ⅴ型3例,除B組4例院外治療其余病例均入院治療。5例ESR升高,平均43.0±19.5(21～64)mm/h。18例HS-CRP升高,平均15.1±12.1(3.2～46.58)mg/1。23例患者sIL-2R均升高,平均570.5±194.6(222.1～935.8)pg/ml。每人接受NPWT治療14～28天,平均20.3±5.2天。5例接受手術(shù)治療。3例接受PCD治療。隨訪19-41個(gè)月,平均30.7±5.9個(gè)月。末次隨訪,所有患者切口愈合后無(wú)竇道形成,術(shù)后無(wú)膿腫及病變無(wú)復(fù)發(fā)。結(jié)論1.NPWT可以促進(jìn)深層結(jié)核性創(chuàng)面愈合,使治療和護(hù)理更簡(jiǎn)單、容易、有效。其中機(jī)制包括(1)減少結(jié)核分枝桿菌數(shù)量,減緩創(chuàng)面病情進(jìn)展,阻斷結(jié)核菌臨近組織傳播；(2)持續(xù)的清除膿液及壞死組織；(3)促進(jìn)創(chuàng)面肉芽組織、膠原生成及新生血管功能化NPWT輔助治療骶髂關(guān)節(jié)結(jié)核并創(chuàng)面比常規(guī)換藥更有效,但仍需要進(jìn)一步的研究確認(rèn)：2.復(fù)治脊柱結(jié)核伴創(chuàng)面患者HS-CRP明顯低于初治脊柱結(jié)核患者,稍高于正常值,這與外周.血IL-6為主的促炎癥因子顯著降低有關(guān)；復(fù)治脊柱結(jié)核伴創(chuàng)面患者CD4/CD8顯著低于正常人群和初治脊柱結(jié)核患者,表明復(fù)治脊柱結(jié)核伴創(chuàng)面患者免疫系統(tǒng)呈現(xiàn)明顯抑制狀態(tài)。監(jiān)測(cè)外周血各免疫因子發(fā)現(xiàn)初治脊柱結(jié)核、復(fù)治脊柱結(jié)核伴創(chuàng)面患者外周血均呈Thl狀態(tài),推斷其局部均為Th2狀態(tài),復(fù)治患者Th2狀態(tài)更明顯。3.根據(jù)T0點(diǎn)復(fù)治脊柱結(jié)核伴創(chuàng)面患者血清中各免疫指標(biāo)較正常值的差異,初步篩選出Hs-CRP、sIL-2R、IFN-γ為監(jiān)測(cè)病情變化的動(dòng)態(tài)指標(biāo)。在T0、Tl、T3點(diǎn),sIL-2R與近期療效指標(biāo)的相關(guān)性優(yōu)于Hs-CRP和IFN-γ, Hs-CRP明顯優(yōu)于IFN-γ, sIL-2R和Hs-CRP可以作為判斷復(fù)治脊柱結(jié)核伴創(chuàng)面患者療效的動(dòng)態(tài)指標(biāo)。4.基于SMU分型和sIL-2R等血清學(xué)指標(biāo),對(duì)脊柱結(jié)核伴創(chuàng)面患者進(jìn)行個(gè)體化治療,將NPWT、PCD、個(gè)體化手術(shù)緊密有序的結(jié)合起來(lái),可以簡(jiǎn)化治療程序,提高治療效果。經(jīng)過(guò)回顧性研究發(fā)現(xiàn)脊柱結(jié)核伴創(chuàng)面的個(gè)體化治療效果顯著,患者均獲臨床治愈,未再次出現(xiàn)復(fù)發(fā)復(fù)治情況。但本研究病例數(shù)較少且為回顧性,仍需進(jìn)一步行多中心大樣本隨機(jī)對(duì)照研究。
[Abstract]:The research background of tuberculous extrapulmonary tuberculosis wounds is a common complication, with characteristic big mouth on the end, often connected with the primary lesion of abscess cavity through the sinus tract channel network perplexing, so the tuberculous wound visible surface is only a corner of the iceberg. While the deep lesions especially for refractory tuberculous wounds, with sacroiliac joint tuberculosis, spinal tuberculosis as the primary focus, this study aims at exploration of deep wounds with tuberculosis. The traditional treatment method with conservative therapy, long treatment effect is poor, often persistent, eventually still need skin flap or muscle flap in wound closure. In recent years with negative pressure wound therapy (Negative pressure wound therapy, NPWT) the rise of a few researchers to explore the application of NPWT treatment of tuberculous wound, but only a series of research on small sample cases, the mechanism is not clear. This study by NPWT treatment of sacroiliac joint tuberculosis wound The self control study on the effectiveness of deep wound tuberculosis and mechanism of clear NPWT state and effect evaluation index of immune related immune system by NPWT for the treatment of recurrent spinal tuberculosis with wound retreatment tuberculosis wound deep clear, by exploring the effectiveness and mechanism of deep wound wound spinal tuberculosis diagnosis and treatment strategy of spinal tuberculosis SMU clear type sIL-2R standard and individualized treatment process objective: 1. to investigate NPWT treatment of sacroiliac joint tuberculosis were based on; 2. to investigate the immune system and immune factor dynamic change process of NPWT for the treatment of recurrent spinal tuberculosis with wounds, index screening can accurately judge the condition change; 3. of the SMU type and sIL-2R and other indicators of individual diagnosis and treatment strategy of spinal tuberculosis wounds of 1. sacroiliac joint tuberculosis based on chronic refractory sinus were back 欏炬，

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