BACKGROUND: Returning stenosis in Crohn's disease (CD) patients is poorly understood. After resection, newly developed strictures are seen within 10 years in 50% to 70%. Matrix metalloproteinases (MMPs) are involved in matrix-turnover processes. This study analyzes spatial expression of MMP-1, MMP-3, MMP-9, tissue inhibitor of MMP-1, and collagen III to get better insight in tissue remodeling of terminal ileum of CD patients. METHODS: Expressions were analyzed on mRNA and the protein level (MMP-1, MMP-3) in segments from resected terminal ileum from CD and control patients. In CD, macroscopic distinction was made between proximal resection margin, prestenotic, and stenotic tissue. Immunohistochemistry allowed for expression analyses transmurally. RESULTS: MMP-1 and MMP-3 gene expression was up-regulated (P < 0.05) in both prestenotic and stenotic tissue. MMP-1 protein was significantly up-regulated in submucosal and muscular tissue of prestenotic parts and in muscular tissue of stenotic Crohn samples. MMP-3 protein was significantly up-regulated in all layers of prestenotic and stenotic Crohn samples. Even in submucosa of proximal resection margin tissue, MMP-3 expression was significantly higher than in controls. CONCLUSION: Surprisingly, in proximal resection margin tissue up-regulated MMP-3 was seen. This suggests that in nonresected terminal ileum, in which anastomosis is made, tissue turnover is present, which may account for the high recurrence of intestinal strictures.
\n \n\n \n \nWith more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage.
\n \n\n \n \nBACKGROUND: Prosthetic meshes are increasingly popular in abdominal wall reconstructive surgery owing to a reduction in hernia recurrence rate. Individual meshes have been evaluated with respect to the formation of infectious biofilms, but no comprehensive comparison yet exists. The aim of this study was to evaluate the effect of the material and morphology of surgical meshes on biofilm growth. METHODS: Biofilms of a coagulase-negative staphylococcus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were grown in vitro on different meshes. Intact biofilms were stained fluorescently and evaluated with confocal laser scanning microscopy to distinguish dead from live bacteria and slime. RESULTS: Numbers of adhering bacteria and the amount of slime in the biofilm were dependent on the morphology of the mesh. Hydrophobicity and the presence of niches in multifilament meshes contributed most to increased biofilm growth. CONCLUSION: The morphological properties of surgical meshes as well as their hydrophobicity influence bacterial growth and slime production. Differences in slime production may explain why the effectiveness of antibiotic treatment varies for different types of mesh.
\n \n\n \n \nStatic cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.
\n \n\n \n \nBACKGROUND: Up to 75% of patients with Crohn's disease (CD) will have intestinal resection during their life. Most patients will, however, develop postoperative recurrence (endoscopic, clinical or surgical). Several medical and surgical strategies have been attempted to prevent postoperative recurrence. This review evaluates the efficacy of different drug regimens and surgical techniques in the prevention of clinical, endoscopic and surgical postoperative recurrence of CD. METHODS: A literature search for randomized controlled trials on medical or surgical interventions was performed. The endpoints for efficacy were clinical, endoscopic and surgical recurrence. Meta-analyses were performed in case two or more RCTs evaluated the same drug or surgical technique. RESULTS: Mesalamine is more effective in preventing clinical recurrence than placebo (P=0,012), as well as nitroimidazolic antibiotics at one year follow-up (P<0.001) and thiopurines (P=0.018). Nitroimidazolic antibiotics are also more effective than placebo in preventing endoscopic recurrence (P=0.037), as well as thiopurines (P=0.015) and infliximab (P=0.006). Budenoside, probiotics, Interleukin-10 nor any of the different surgical procedures showed any significant difference compared to placebo in postoperative recurrence rates of CD. CONCLUSION: Among the different drug regimens and surgical techniques, only thiopurines and nitroimidazolic antibiotics are able to reduce postoperative clinical as well as endoscopic recurrence of CD. Mesalamine and infliximab also seem to be superior to placebo in preventing clinical recurrence and endoscopic recurrence, respectively. There is a paucity of trials evaluating long-term follow-up and prevention of surgical recurrence of CD.
\n \n\n \n \nBACKGROUND: Kidneys derived from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Strikingly, early and profound serum levels of IL-6 in brain-dead donors are observed. IL-6 is the main regulator of the acute phase response (APR). The aim of this translational study was to investigate the expression of renal acute phase proteins (APPs) following brain death (BD) and to assess the association with renal allograft outcome after transplantation. METHODS: BD was induced in rats by inflating a subdurally placed balloon catheter. Kidney biopsies were obtained from human living and brain-dead donors at donation, after cold preservation and reperfusion. In vitro, renal proximal tubular epithelial cells (HK-2 cells) were stimulated with IL-6. RESULTS: Both in human and rat brain-dead donors, C3 and FBG expression was enhanced at donation compared to living donors and sham-operated animals. In human donors, no additional expression was found after cold ischaemia or reperfusion. C3 expression after reperfusion was independently associated with decreased short-term function after transplantation in grafts from brain-dead donors. In cultured HK-2 cells, C3 production was induced in the presence of IL-6. CONCLUSIONS: In conclusion, BD induces renal C3 and FBG expression. Moreover, C3 expression is associated with a worse allograft function early after transplantation. Therefore, targeting renal APPs in brain-dead donors, especially complement C3, may improve transplant outcome.
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