Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia–reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (− 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.

Remote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P < 0.05; number of master junctions, P < 0.05; number of segments, P < 0.05) but were not influenced by culture medium from RIPC/cRIPC treated monocytes. While RIPC/cRIPC treatment did not lead to significant changes of the median plasma concentrations of any of the selected potentially pro-angiogenic humoral factors, in-depth analysis of the individual subjects revealed differences in plasma levels of IL-1α, CXCL5 and Growth hormone after RIPC/cRIPC treatment in some of the volunteers. Nevertheless, the positive effects of RIPC/cRIPC plasma on in-vitro angiogenesis could not be mimicked by the addition of the respective humoral factors alone or in combination. While monocyte conditioned culture media did not affect in-vitro tube formation, flow cytometry analyses of circulating monocytes revealed a significant increase in the number of Tie-2 positive and a decrease of CCR2 positive monocytes after RIPC/cRIPC (Tie-2: cRIPC, P < 0.05; CCR2: RIPC P < 0.01). Cardiovascular protection may be mediated by RIPC and cRIPC via a regulation of plasma cytokines as well as changes in cell surface characteristics of monocytes (e.g. Tie-2). Our results suggest that a combination of humoral and cellular factors could be responsible for the RIPC/cRIPC mediated effects and that interindividual variations seem to play a considerable part in the RIPC/cRIPC associated mechanisms.

The MMI Symani^® is a recently approved robotic microsurgical system for surgical procedures in adults. The system enables the surgeon to create microanastomoses. Clinical applications so far include lymphatic vessels surgery and the creation of special flap plastics. The use of the system in coronary arteries has not yet been assessed. The aim of this preclinical study was to evaluate the applicability of the Symani^® surgical system in the creation of coronary anastomoses a cadaveric porcine model. A total of 12 anastomoses were performed by three senior cardiovascular surgeons on the left main coronary artery of three porcine hearts. Artificial bypasses (diameter 1 mm) were performed to the left main trunk. The anastomoses were performed with the Symani^® surgical system. Evaluation included procedure times and anastomosis leakage. All anastomoses could be successfully performed. The procedure time decreased due to the learning curve between the first anastomosis 47:28 ± 5:30 min and the last anastomosis 22:37 ± 3:25 min. The final evaluation of the anastomoses showed excellent results with low leakage. The quality of the anastomosis also improved in relation to the increasing learning curve. The Symani^® surgical system could be used to create coronary anastomoses in an acceptable time frame and without technical failures. Hence, the system appears feasible for conventional coronary surgery. Further studies in animal models are mandatory prior to clinical application.

Vivostat Platelet-Rich Fibrin^® (PRF) is an autologous platelet concentrate used for the local treatment of chronic or complicated wounds. Still, its application for this indication is not evidence-based. Therefore, we performed this monocentric retrospective pilot study investigating the clinical outcome of a local treatment of chronic or complicated wounds in 35 patients (23 male, 12 female, mean age 68.7 years) treated with Vivostat PRF^®. This study population is the largest among published studies analyzing the clinical efficacy of Vivostat PRF^® on chronic wounds so far. Using the perpendicular method we divided the wounds into three sizes (30 cm²). The clinical efficacy of the Vivostat PRF treatment was the primary endpoint and was divided into three groups of increasing degrees of wound improvement: (1) no improvement of the wound (wound area was not reduced > 10% under Vivostat PRF^® treatment), (2) improvement of the wound (reduced area > 10% under Vivostat PRF^® treatment) and (3) complete epithelialization (wounds that were completely re-epithelialized after Vivostat PRF^® treatment). We included patients’ diagnosis and concomitant diseases (peripheral arterial occlusive disease (PAOD)), chronic venous insufficiency (CVI)), diabetic foot syndrome (DFS)) in our data analysis in order to investigate their potential impact on the wound healing capacity of Vivostat PRF^®. Our results show that in the entire study population, 13 out of 35 (37.1%) patients experienced wound improvement and 14 out of 35 (40%) patients showed complete epithelialization of their wound under Vivostat PRF^® treatment. In summary, 77.1% of the treated patients benefited from the Vivostat PRF^® therapy. These positive wound healing effects were all observed within the first three to six Vivostat PRF^® applications. Subgroup analyses showed that Vivostat PRF^® appeared to be more efficient in patients without CVI in comparison to patients with CVI (p = 0.02). Moreover, Vivostat PRF^® treatment seems to be particularly efficient in PAOD-related wounds with a reduced crural arterial blood supply (p = 0.01). Additionally, we performed an experimental human in vivo study on ten male students where we artificially generated bilateral gluteal wounds and analyzed the influence of the Vivostat PRF^® treatment on the expression of two genes (human beta Defensin-2, ((hBD-2) and human beta-Defensin-3 (hBD-3)) in keratinocytes of resected wound specimens that are induced during wound healing. Interestingly, this analysis revealed that only seven of out ten individuals showed a relevant hBD-2 and hBD-3 gene induction after Vivostat PRF^® treatment. This led to the novel “key-lock-hypothesis”. With the goal of an individualized precision medicine approach with optimized wound treatment strategies in the future, this is an important observation that demands further experimental and clinical studies.

Background: Men are known to have a higher incidence of acute cardiovascular events, while women are recognized for their increased mortality following diagnosis or intervention for these conditions. The aim of this study is to explore the sex differences in clinical profiles and outcomes of patients undergoing ascending aortic aneurysm (AscAA) surgery. Methods: A PRISMA compliant literature search and data extraction were conducted using PubMed, EMBASE, and SCOPUS. Observational cohort or retrospective registries that compared a defined number of male and female adults undergoing ascending aortic surgery for AscAA were included. Data analysis was conducted in compliance with Cochrane methods. Results: A total of 11 unique studies met the inclusion criteria, from which 13636 patients were included, with a distribution of 9124 males (67%) and 4512 females (33%). Overall, 91% underwent elective surgery. Male patients had significantly lower 30-day mortality, (RR: 0.68, 95% Cl [0.57, 0.81], p < 0.0001) and shorter stays in the intensive care unit, with a mean difference (MD) of −0.48 days ([−0.84, −0.13], p = 0.008). Males were significantly younger at the time of surgery (MD: −3.94 years, 95% CI [−5.58, −2.31], p < 0.00001). Male patients had significantly more frequent concomitant CABG (21% vs. 14.5%; p < 0.0001), while females had more frequent isolated supra-coronary ascending aortic replacement (22% vs. 36%; p = 0.004). Female patients who underwent AscAA surgery had significantly lower long-term survival (HR: 1.25, [1.05, 1.50], p = 0.013). Conclusions: Women undergo surgery for AscAA at older ages and face greater mortality. The disparities in preoperative age and timing of surgery between males and females can be explained by differences in comorbidity profiles and the need for concomitant surgery.