The Research And Application Of The Effect Of Negative Pressure Wound Therapy In Deep Tuberculosis Wounds

BackgroundTuberculous wound is a common complication of extrapulmonary tuberculosis. The characteristics are the small outflow and the big bottom of the wound. Tuberculous woundusually associated with the abscess cavity of primary lesions through the sinus tracts.Therefore tuberculous wound on the surface is just a corner of iceberg. And the deep tuberculous wounds which contain the sacroiliac joint tuberculosis or the spinal tuberculosis are particularly difficult to treat. So we started this research for the treatment of deep tuberculous wounds. The traditional method of treatment for tuberculous wound is conservative therapy. But the problem are the long course of treatment and the poor curative effect.Sometimes It still needs skin flap grafting or muscle flap grafting in wound closure at last. In recent years,with the rise of negative pressure wound therapy,a few researchers explored the application of negative pressure wound therapy in the treatment of tuberculous wound.But the articles belong to case series research and have small sample size.And the mechanisms of wound healing are still unknown. This study intends to understand the effectiveness and mechanism of negative pressure wound therapy in the treatment of deep tuberculosis through a self-control study of the negative pressure wound therapy in the treatment of sacroiliac joint tuberculosis and with wound, to clarify the immune system status and curative effect evaluation indexes of the retreatment deep tuberculous wound through the immune correlation study of negative pressure wound therapy in the treatment of the retreatment spinal tuberculosis with wound、 to establish the standardized and individualized diagnosis and treatment of deep wound of spinal tuberculosis by exploring the strategy for the diagnosis and treatment of spinal tuberculosis with wound based on the classification of SMU and sIL-2R.Objective1. To investigate the effectiveness and mechanism of negative pressure wound therapy in the treatment of the sacroiliac joint tuberculosis with wound.2. to investigate the dynamic changes of the immune system and immune factors in the process of negative pressure wound therapy in the treatment of retreatment spinal tuberculosis with wound and filter the relevant indicators of the accurate judgment of the condition changes.3. To investigate the individualized treatment strategy of the spinal tuberculosis with wound based on the SMU classification and sIL-2R.Methods1. Perform the self control study for the sacroiliac joint tuberculosis with chronic refractory sinus treated by negative pressure wound therapy and collect the general condition of patients. Each patient experienced the control phase,the interphase and the intervention phase. ESR,hs-CRP,wound size,drainage,microvessel density (MVD),collagen volume ratio were compared in the control phase and the intervention phase.2. Patients with spinal tuberculosis wound who were cured by negative pressure wound therapy were brought into the treatment group. Patients with spinal tuberculosis and the healthy adults were as the control groups. The time points of TO,T1,T3 were defined at different times. The T cell subsets,ESR and Hs-CRP were compared among the three groups at TO point. TNF-α、IL-2、IFN-γ、IL-12、IL-4、 IL-6、IL-10 and sIL-2R were compared among the three groups at TO point. Analysis linear correlation between Hs-CRP、IFN-γ or sIL-2R in every group at TO,T1,T3 point and BMI in the corresponding group at the corresponding time point. Analysis linear correlation between Hs-CRPT1-T0、IFN-γT1-T0 orsIL-2RTT1-T0 and The wound drainage(T1-T0), VAST1-T0 or spinal lesion volume(T1-T0).3. Spinal tuberculosis with wounds were divided into A,B,C,D groups by SMU and initial treatment or retreatment cases. And according to the individualized diagnostic and therapeutic strategies the treatment was performed.Initial treatment patients were monitored by ESR,Hs-CRP and retreatment patients were monitored by Hs-CRP, sIL-2R. And the indexes determined the NPWT course, whether they need the radical debridement operation and the opportunity to close the wound. Collect the general information and be followed up.Results1. The sinus formation time was 3 to 6 months (mean 3.92±1.08 months).The treatment time was 14 to 35 days (mean 18.33±6.97). The sinus closed time was 20 to 42 days after NPWT (average 25.25±7.23 NPWT). After NPWT treatment,the CD34 immunohistochemical stainings of wound tissues showed that the number of wound angiogenesis was no significant change than before,but more functional and more effective angiogenesis were obtained. After NPWT treatment,the wound collagen volume ratio was significantly higher than that before NPWT treatment (P<0.001).And the curative effect is better than dressing change. At the intervention phase the daily volume of drainage in the first three days was increased from 22.33±7.28ml to 29.17±16.63ml and then decreased from 29.17±16.63ml to 0.25±0.87ml at the 35th day. The wound volume was fell from 34.08±33.91cm3 to 25.50±26.04cm3 (P< 0.05). After NPWT treatment the wound volume was reduced 26.98%.ESR significantly was reduced from38.33±20.82 to 25.50±11.72 mm/h (P< 0.05); Hs-CRP significantly was reduced from 33.67±11.72 to 13.00±8.01mg/l (P< 0.05). The wound volume,ESR,Hs-CRP of the intervention phase were significantly lower than in the control period (P< 0.05).2. At TO point there were no significant difference in ESR between group A and group C. ESR in group A was significantly lower than in group B (P< 0.05). Hs-CRP in group A was significantly lower than in group B (P< 0.05). Although Hs-CRP in group A was closed to the normal value,There was significant difference in Hs-CRP between group A and group C (P< 0.05). In TO point,the CD8 in group B was significantly higher than in group C(P<0.001). There was no significant difference in CD4 between the two groups. The CD4/CD8 in group B was significantly lower than in group C(P< 0.05). The ratio of CD4 in group A was significantly lower than in group B(P<0.001). There was no significant difference in CD8 ratio between the two groups. The CD4/CD8 in group A was significantly lower than in group B(P<0.05). The ratio of CD8 in group A was significantly higher than in group C(P<0.001). The ratio of CD4 in group A was significantly lower than in group C(P<0.01). The CD4/CD8 in group A was significantly lower than in group C(P<0.01). sIL-2R and IFN-y in group A was significantly higher than in group C(P<0.05). IL-6 in group A was significantly lower than that in group C (P<0.05). At TO point in group A sIL-2R, IFN-γ. HS-CRP were negative correlation with BMI. (P<0.05); At T1 point in group A sIL-2R and HS-CRP were negative correlation with BMI. At T3 point in group A only sIL-2R was negative correlation with BMI. HS-CRPT1-T0 and drainage volume(T1-T0) were positively correlated (P< 0.05). HS-CRPT1-T0 and VAST1-T0 were positively correlated (P< 0.05). sIL-2RT1-T0 and VAST1-T0 were positively correlated (P< 0.001).3. According to the classification of SMU and initial treatment or retreatment,1 patient in group A was belong to initial treatment and SMU Ⅰ, Ⅱ type.17 patients in group B was belong to retreatment and SMU Ⅰ、Ⅱ、Ⅲa type.17 patients in group B was belong to retreatment and SMU Ⅰ、Ⅱ、Ⅲa type.2 patients in group C was belong to initial treatment and SMUⅢ、Ⅳ、Ⅴ type.3 patients in group D was belong to retreatment and SMU Ⅲb、Ⅲc、Ⅳ、Ⅴ type. In addition to 4 external hospital treatment cases in the group B,the rest of the group B patients were admitted to hospital treatment. ESR was increased in 5 cases. The average of ESR was 4.3±19.5 (21-64) mm/h. HS-CRP was increased in 18 cases. The average of HS-CRP was 15.1±12.1(3.2-46.58)mg/l. sIL-2R was increased in all cases. The average of sIL-2R was 570.5±194.6(222.1-935.8)pg/ml. An average duration of NPWT was 20.3±5.2 (14-28) days.5 cases received surgical treatment.3 cases were treated by PCD. Followed up for average 30.7±5.9 (19-41) months. At the last follow-up,there were no sinus formation after wound healing,no postoperative abscess and no recurrence in all patients.Conclusion1. NPWT can promote deep tuberculous wound healing and make the treatment and nursing more simple,easy,and effective. The mechanism may include (1) reducing the bioburden of Mycobacterium tuberculosis,slowing the deterioration of wound,blocking the organizational communication near lesion; (2) removing pus and necrotic tissue continually;(3) promoting the formation of wound granulation tissue and collagen and functional neovascularization.NPWT in the treatment of sacroiliac joint tuberculosis was more effective than the conventional dressing. But further study is still needed to confirm.2. ESR of the retreatment spinal tuberculosis with wound was in the normal range,which may be associated with the balance of tissue injury and repair. HS-CRP of the retreatment spinal tuberculosis with wound was lower than initial spinal tuberculosis and slightly higher than the normal range,that may be related to the significant reduction of the peripheral blood IL-6 which is the proinflammatory factor. CD4/CD8 of retreatment spinal tuberculosis with wound was significantly lower than normal population and initial treatment spinal tuberculosis,which meaned the immune system of patient with retreatment spinal tuberculosis with wound showed significantly inhibited state. Monitoring peripheral blood immune factor found the peripheral blood of initial treatment spinal tuberculosis and retreatment spinal tuberculosis with wound showed a Thl state. It was concluded that the local lesion was Th2 state.Retreatment patients had more obvious Th2 status,which may be related to the decreased CD4/CD8.3. According to the differences of the immune indexes serum levels between that in the patients retreatment of spinal tuberculosis with wound and in normal patients at TO points. Preliminary screening showed that Hs-CRP,sIL-2R,IFN-y may be used for dynamicly monitoring the disease condition.The correlation between sIL-2R and short-term therapeutic effect was better than that of Hs-CRP and IFN-y. Hs-CRP was superior to IFN-y.SIL-2R and Hs-CRP can be used as dynamic indexes to judge the curative effect of the retreatment spinal tuberculosis with wound.4. Based on SMU,sIL-2R and other serological indicators,perform individualize treatment of spinal tuberculosis with wound and make NPWT,PCD,the individual operation band together can simplify the treatment process and improve the treatment effect. After retrospective study found that individualized treatment of spinal tuberculosis with wound is remarkable. All the patients were cured and did not appear relapse and recurrent conditions. But the number of cases of the retrospective study is few. And more multicenter,large sample,randomized and controlled clinical researches are needed.