Hemostatic Efficacy and Biocompatibility Evaluation of a Novel Absorbable Porous Starch Hemostat

Background A novel absorbable porous starch hemostat (APSH) based on calcium ion-exchange crosslinked porous starch microparticles (Ca2+CPSM) was developed to improve hemostasis during surgeries for irregular cuts. The aim of this study was to compare its hemostatic efficacy and biocompatibility in a standard rat liver injury model relatively to Arista AH, Quickclean, and crosslinked porous starch microparticles (CPSM, without calcium ion). Methods 72 Wistar rats (220g–240 g) were randomly assigned to six groups (Arista, Quickclean, CPSM, Ca2+CPSM, native potato starch, and untreated control group, n =12 per group). 30 mg of each hemostatic agent was applied to a standard circular liver excision (8 mm in diameter and 3 mm deep) in rats. Following their hemostatic efficacy, in vivo biocompatiblity evaluation was examined. The native potato starch (NPS) group was used as the negative group. Results Ca2+CPSM had almost the same hemostatic efficacy compared with Arista; meanwhile, all the 4 hemostatic agents had good blood compatibility. In terms of in vivo tissue compatibility, Ca2+CPSM had relatively fast degradation and absorption rate with good histocompatibility. As the morphological, anatomic observation and H&E staining of liver defects after implantation, Ca2+CPSM was almost completely absorbed by liver tissue after 14 days. Conclusion According to our study, Ca2+CPSM could effectively achieve hemostasis in the standard rat liver injury model and exhibited good blood compatibility and in vivo tissue compatibility. These finding suggested that Ca2+CPSM as a new kind of APSH had its extensive clinical application value.

Photosensitizers and Exposure Times To Light Showed Tissue Compatibility In Isogenic Mice

Objective: The aim of this study was to evaluate the subcutaneous tissue response after different protocols to photodynamic therapy (PDT). In Phase 1, were tested the diode laser (used for 1min) associated to the photosensitizer phenothiazine chloride solution (PCS) in different concentrations. In Phase 2 – the diode laser and LED were tested associated to two different photosensitizers, PCS and Curcumin, in different exposure times of light application. Material and Methods: After 7, 21 and 63-days the animals were euthanized and the subcutaneous tissue processed to histological analysis. Qualitative and semi-quantitative descriptions of the inflammatory process and immunohistochemical technique were performed. The obtained data were analyzed by Kruskal-Wallis and Dunn’s post-test (alpha = 0.5). Results: On Phase 1, the tissue response was very similar among the groups. For the inflammatory infiltrate, PCS with concentration of 10mg/mL exhibited the most intense reaction (p > 0.05). On Phase 2, at 7-days period, the analyzed parameters presented small magnitude and after 21 and 63-days, all the parameters demonstrated tissue compatibility. Conclusion: Both photosensitizers presented proper tissue compatibility regardless the different concentrations used on Phase 1 and different durations of light exposure on Phase 2. Keywords Photodynamic therapy; Phenothiazine chloride solution; Curcumin; Isogenic mice; Subcutaneous tissue.

P1610THE PERSPECTIVE APPROACH TO ASSESING THE DONOR-RECIPIENT HISTOCOMPATIBILITY IN CADAVERIC KIDNEY TRANSPLANTATION

Background In Russia, each transplant center has its own separated waiting list. This significantly reduces the ability to select the optimal recipient in terms of tissue compatibility. Aim to perform a multivariate analysis of the effect of the number of epitope mismatches on transplant survival. Method An observational retrospective cohort study was performed, which included 824 adult recipients. All patients underwent transplantation of a cadaveric kidney compatible by blood group. The endpoint was considered transplant loss. The death-censored graft survival was evaluated. The calculation of the number of epitope mismatches (EpMM) was carried out using information from publicly available resources about the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. Then, for each combination with nonzero probability the number of donor epitopes absent in the recipient was determined. After that, the weighted average EpMM was calculated, where the weighted coefficient was the normalized probability of occurrence of each combination. Results All recipient donor pairs had HLA incompatibilities (HLA MM): 1.9% - 1 HLA MM, 6.7% - 2 HLA MM, 29.9% - 3 HLA MM, 38.5% - 4 HLA MM, 18, 1% - 5 HLA MM, 4.9% - 6 HLA MM. EpMM increased with increase of the HLA MM count, but not linearly: 6 [interquartile range – IQR 4; 7] (from 2 to 7), 12 [IQR 7.74; 17.25] (from 4 to 20), 18 [IQR 14; 22] (from 8 to 28), 24 [IQR 20; 30] (from 10 to 33), 30.5 [IQR 25; 37] (from 13 to 35) and 36 [IQR 26.5; 44.5] (from 15 to 40) for 1, 2, 3, 4, 5, and 6 HLA MM, respectively. Significant risk factors for graft loss in the adjusted multivariate model were: HLA MM (1 – HR 1; 2– HR 1.24 [95% confidence interval - 95% CI 0.7; 2.15], p = 0.344; 3– HR 1, 48 [95% CI 0.86; 2.33], p = 0.251; 4– HR 1.88 [95% CI 1.32; 2.52], p <0.001; 5– HR 2.41 [95 % CI 2; 2.93], p <0.001; 6– HR 2.98 [95% CI 2.59; 3.46], p <0.001) p <0.001; duration of conservation HR 1.08 per hour [95% CI 1.02; 1.16], p = 0.01; panel-reactive antibodies (PRA) HR 1.24 per every 10% [95% CI 1.06; 1.58], p = 0.01; but not the type of donor, age and gender of the recipient. When included EpMM in the model, significant risk factors were: EpMM (<10– HR 1; 10-19– HR 1.71 [95% CI 1.09; 2.49], p = 0.021; 20-29– HR 2,11 [95% CI 1.59; 2.68], p <0.001; 30-39– HR 2.4 [95% CI 1.96; 2.86], p <0.001; 40-49– HR 2, 59 [95% CI 2.17; 3.04], p <0.001; ≥50– HR 2.71 [95% CI 2.31; 3.15], p <0.001) p <0.001; PRA HR 1.18 for every 10% [95% CI 1.09; 1.5], p = 0.007; but not the duration of conservation, donor type, age and gender of the recipient. However, HLA MM was no longer a significant risk factor for HR graft loss 1.19 [95% CI 0.88; 1.55], p = 0.451. Increasing the EpMM from <10 to 10-19 significantly increases the risk of graft loss. This is an important aspect in the context of our study, since the number of EpMM 10-19 can correspond to 2-6 HLA MM. Validation of this method of assessing immunological load on a larger sample of patients is required. The list of immunogenic epitopes is constantly updated. The accumulation of this knowledge can improve results of transplantation. Conclusion The number of epitope mismatches remains an important factor in long-term transplant survival even when adjusted for other risk factors: the number of HLA mismatches, the donor type and the level of presensitization. This determines the possibility of using this method as an adjuvant in the donor-recipient pair selection. At the same time, there is a theoretical possibility of using this method as an alternative to the traditional assessment of tissue compatibility of a donor and a recipient.