Background:The impact of previous radiotherapy on free flap outcome is still a subject of debate. Clinical investigations have come to divergent conclusions and the true effect of radiotherapy (XRT) on flap survival is not definitely known. Most studies investigating the factor often have their methodological limitations such as lack of statistical power as a consequence of the overall low failure rates together with few irradiated cases. This study will attempt to address the question whether previous radiotherapy is associated with a significantly higher incidence of flap failure or not. Methods: A systematic review and meta-analysis were conducted in concordance with the PRISMA protocol using the PubMed database. Fixed-effect and randomeffect models were applied to obtain the odds ratio of total flap failure and partial flap failure between radiation and nonradiation groups. Statistical heterogeneity and publication bias were assessed and forest plots and funnel plots were constructed for graphic illustration. Results: A total of 43 studies were included for qualitative and quantitative analysis involving 18,776 flaps in 17,532 patients. Patients with preoperative XRT were significantly associated with an increased risk for total (odds ratio fixed = 1.675, 95% confidence interval [CI] = 1.405-1.996, P < 0.001) and partial free flap failure (odds ratio fixed = 2.161, 95% CI = 1.472-2.172, P < 0.001). Conclusion:The study suggests that preoperative radiotherapy is associated with an increased risk for total and partial free flap failure. Further studies are needed to investigate the effect of total XRT dose and time after radiation on free flap outcome.

<b><i>Background:</i></b> Postoperative pancreatic fistula (POPF) is a major complication in pancreatic surgery and can cause considerable postoperative morbidity. Advanced surgical-technical approaches to prevent POPF did not yield a substantial improvement. To investigate innovative treatments, experimental animal models of distal pancreatic resection and pancreaticoduodenectomy are of fundamental importance. After a failed attempt to replicate a previously described rat model for pancreatic fistula induction, we proceeded to distal pancreatic resection with splenectomy to provoke pancreatic leakage and generate a suitable animal model. <b><i>Methods:</i></b> Distal pancreatic resection with splenectomy was performed in 40 rats. The rats were sacrificed on postoperative day (POD) 1, 2, 4, 6, 8, or 10, and the abdominal cavity was explored. Ascites probes were collected pre- and postoperatively for the detection of pancreas amylase and lipase. Tissue samples from the naïve pancreas (POD 0) and the postoperatively harvested remnant were evaluated histologically. The extent of necrosis was determined, and samples were examined for neutrophil infiltration. TUNEL staining served for the verification of necrosis in distinct cases. Immunohistochemistry of Ki67, von Willebrand factor, and CD68 was performed to evaluate proliferation, blood-vessel sprouting, and macrophage invasion. <b><i>Results:</i></b> The rats showed no clinical symptoms or severe complications in the postoperative course up to 10 days. Abdominal exploration revealed adhesions in the upper abdomen, but no intra-abdominal fluid accumulations were found. Signs of inflammation and tissue damage were evident at the pancreatic resection margin on histological examination whereas the naïve pancreatic tissue was widely unaffected. Statistically significant differences were seen between the preoperative and postoperative extent of necrosis, the presence of neutrophil infiltrate, and levels of ascitic amylase and lipase. Immunohistochemical staining on Ki67, von Willebrand factor, and CD68 did not reveal any workable results on nonstatistical examination, and it was therefore not considered for further analyses. <b><i>Conclusion:</i></b> Creating a functional animal model of pancreatic fistula that reflects the clinical and pathophysiological impact of pancreatic leakage in humans has not been achieved. Our approach of left pancreatic resection recapitulated inflammation and tissue damage, early events in the development of fistulas, and it could be suitable for the experimental testing of novel targeting methods.

Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A—also called progerin—causes Hutchinson–Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expressed in the blood of healthy individuals due to alternative splicing. Previously, we found an association of increased progerin mRNA with overweight and chronic inflammation (hs-CRP). Here, we aimed to elucidate correlations of ZMPSTE24, lamin A/C and progerin with the inflammatory marker hs-CRP. In this retrospective, cross-sectional study we analyzed blood samples from 110 heart failure patients for quantitative mRNA expression of ZMPSTE24, lamin A/C, progerin and hs-CRP protein. Spearman correlations and linear regression analyses including adjustments for age, gender and ejection fraction showed a significant positive correlation of lnprogerin with lnZMPSTE24 (n = 110; r = 0.33; p = 0.0004) and lnlamin A/C (n = 110; r = 0.82, p < 0.0001), whereas no association was observed between lnlamin A/C and lnZMPSTE24 expression. Further analyses showed a significant positive correlation of lnhs-CRP with lnZMPSTE24 (n = 110; r = 0.21; p = 0.01) and lnlamin A/C (n = 110; r = 0.24; p = 0.03). We conclude that chronic inflammation is associated with increased expression of ZMPSTE24 and lamin A/C mRNA. Both markers also positively correlate with increased expression of the premature aging marker progerin which may be linked to cardiovascular aging.