Vivostat Platelet-Rich Fibrin® for Complicated or Chronic Wounds-A Pilot Study

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

Is total arch replacement associated with an increased risk after acute type A dissection?

Background The surgical strategy for acute type A aortic dissection (AADA) usually consists of reconstruction of the tear-lesion in the affected part of the ascending aorta. The optimal strategy either to replace the ascending aorta (AAR) or to replace the ascending aorta and the total aortic arch (TAAR) is still under debate. Our study compares the 30-day mortality between AAR and TAAR in AADA surgery. Results In 292 (86.1%) patients AAR and in 47 (13.9%) patients TAAR was performed for emergent AADA. Patients were older (P=0.049) in the AAR group. The median log Euro-SCORE was 25.5% (12.7; 41.7) for AAR and 19.7% (11.7; 32.2) for the TAAR patient cohort (P=0.12). Operative time, cardiopulmonary bypass- (CPB), cross-clamp- and ischemic time were significantly longer in the TAAR group (P<0.001). The overall 30-day mortality-rate was 17.7% (n=60) but was not significantly different between the two groups (P=0.27). Forty-nine (16.8%) patients died in the AAR and 11 patients (23.4%) in the TAAR group. After propensity-score matching, no difference in mortality was seen between the subgroups as well (P=0.44). Multivariable analysis identified the Euro-SCORE, long operation-time, postoperative dialysis and arrhythmia and administration of red blood cell concentrates as risk factors for 30-day mortality, but not for TAAR versus AAR. Conclusions The therapeutic goal in AADA surgery should be the complete restoration of the aorta to avoid further long-term complications and re-operations. Though 30-day mortality and postoperative co-morbidity for AAR are comparable to those in TAAR after treatment of AADA in our analysis, decision-making for the surgical strategy should weigh the operative risk of TAAR against the long-term outcome

Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

Background Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. Results I/R-injury decreased intestinal galactose uptake (iIPC group: p<0.001), increased vascular perfusion pressure (iIPC group: p<0.001; eIPC group: p<0.01) and attenuated venous flow (iIPC group: p<0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p<0.001), luminal flow (iIPC group: p<0.001; eIPC group: p<0.05), goblet cell ratio (iIPC group, eIPC group: p<0.001) and apoptosis (iIPC group, eIPC group: p<0.05) were all increased. Application of iIPC prior to I/R increased vascular galactose uptake (P<0.05) while eIPC had no significant impact on parameters of I/R-injury. On cellular level, I/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I/R increased phosphorylation of JNK2 and p38δ while eIPC enhanced CREB and GSK-3α/β phosphorylation. Conclusion Intestinal I/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I/R-injury is rather limited

Recommendations for a standardised educational program in robot assisted gynaecological surgery: consensus from the Society of European Robotic Gynaecological Surgery (SERGS)

Background: the Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. Methods: a Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. Results: on review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. Conclusions: consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery

Imagining tonal spaces: Conceptions of hierarchy, chromaticism, and social constructs in Schubert's music.

This dissertation explores the diverse analytic and hermeneutic methods that music scholars have developed to interpret Schubert's use of tonality. Three interpretive traditions are discussed here: diatonically based theories, chromatic-tonal theories, and hermeneutic approaches. Through the lens of literary theory, philosophy, and historiography, this dissertation asks how these methods, along with various historical frameworks and aesthetic ideological values, have led to different interpretations of tonality and meaning in Schubert's music. This research addresses: (1) what our methods enable us to say about Schubert's music, and what they omit from our discourse; (2) what preconditions influence our conceptions of Schubert's tonal procedures; (3) how seemingly different approaches can suggest similar aesthetic ideological constructs; (4) the extent to which Schubert's music challenges these methods and how scholars have responded to these difficulties; (5) the boundaries between text and context in practices that have been adopted to interpret Schubert's music. In hopes of offering a new path toward understanding Schubert's music, this dissertation proposes an alternative model to the current systems---one based on the concept of dialogic space---which extends writings by Johann Gottlieb Fichte and Friedrich von Schlegel on German romantic irony. To demonstrate this model, this dissertation analyzes several of Schubert's works, including the Moment Musical, op. 94, no. 2, the Sonata in A minor, D. 537, and the Sonata in A Major, D. 959.Ph.D.Communication and the ArtsMusicUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126663/2/3276132.pd

Hypoxia directed migration of human naïve monocytes is associated with an attenuation of cytokine release: indications for a key role of CCL26

Background!#!Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors.!##!Methods!#!Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26. Cell migration was recorded and secretome analyses were performed.!##!Results!#!Cell migration recordings revealed directed migration of monocytes towards the source of hypoxia. Analysis of the monocyte secretome demonstrated a reduced secretion of 70% (19/27) of the analyzed cytokines under hypoxic conditions. The most down-regulated factors were CCL26 (- 99%), CCL1 (- 95%), CX3CL1 (- 95%), CCL17 (- 85%) and XCL1 (- 83%). Administration of recombinant CCL26 abolished the hypoxia-induced directed migration of human monocytes, while the addition of CCL26 under normoxic conditions resulted in a repulsion of monocytes from the source of CCL26.!##!Conclusions!#!Hypoxia induces directed migration of human monocytes in-vitro. Autocrine/paracrine released CCL26 is involved in the hypoxia-mediated monocyte migration and may represent a target molecule for the modulation of monocyte migration in-vivo

Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach

Abstract Backround Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression of various markers of pluripotency. These so-called programmable cells of monocytic origin (PCMO) hold great promise in regenerative therapies. The aim of this translational study was to explore and exploit the functional properties of PCMO for allogeneic cell transplantation therapy in critical limb ischemia (CLI). Methods Using our previously described differentiation protocol, murine and human monocytes were differentiated into PCMO. We examined paracrine secretion of pro-angiogenic and tissue recovery-associated proteins under hypoxia and induction of angiogenesis by PCMO in vitro. Allogeneic cell transplantation of PCMO was performed in a hind limb ischemia mouse model in comparison to cell transplantation of native monocytes and a placebo group. Moreover, we analyzed retrospectively four healing attempts with PCMO in patients with peripheral artery disease (PAD; Rutherford classification, stage 5 and 6). Statistical analysis was performed by using one-way ANOVA, Tukey’s test or the Student’s t test, p < 0.05. Results Cell culture experiments revealed good resilience of PCMO under hypoxia, enhanced paracrine release of pro-angiogenic and tissue recovery-associated proteins and induction of angiogenesis in vitro by PCMO. Animal experiments demonstrated significantly enhanced SO2 saturation, blood flow, neoangiogenesis and tissue recovery after treatment with PCMO compared to treatment with native monocytes and placebo. Finally, first therapeutic application of PCMO in humans demonstrated increased vascular collaterals and improved wound healing in patients with chronic CLI without exaggerated immune response, malignant processes or extended infection after 12 months. In all patients minor and/or major amputations of the lower extremity could be avoided. Conclusions In summary, PCMO improve angiogenesis and tissue recovery in chronic ischemic muscle and first clinical results promise to provide an effective and safe treatment of CLI

Effects of remote ischemic preconditioning (RIPC) and chronic remote ischemic preconditioning (cRIPC) on levels of plasma cytokines, cell surface characteristics of monocytes and in-vitro angiogenesis: a pilot study

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 &amp;gt; 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 &amp;lt; 0.05; number of master junctions, P &amp;lt; 0.05; number of segments, P &amp;lt; 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 &amp;lt; 0.05; CCR2: RIPC P &amp;lt; 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

Additional file 2 of Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach

Table S1. Presenting primers relate to hypoxia-induced gene expression in monocytes/macrophages. (DOCX 308 kb