Purpose. To assess the intraoperative results comparing two non-mechanical laser assisted penetrating keratoplasty approaches in keratoconus and Fuchs dystrophy. Patients and Methods. 68 patients (age 18 to 87 years) with keratoconus or Fuchs dystrophy were randomly distributed to 4 groups. 35 eyes with keratoconus and 33 eyes with Fuchs dystrophy were treated with either excimer laser ([Exc] groups I and II) or femtosecond laser-assisted ([FLAK] groups III and IV) penetrating keratoplasty. Main intraoperative outcome measures included intraoperative decentration, need for additional interrupted sutures, alignment of orientation markers, and intraocular positive pressure (vis a tergo). Results. Intraoperative recipient decentration occurred in 4 eyes of groups III/IV but in none of groups I/II. Additional interrupted sutures were not necessary in groups I/II but in 5 eyes of groups III/IV. Orientation markers were all aligned in groups I/II but were partly misaligned in 8 eyes of groups III/IV. Intraocular positive pressure grade was recognized in 12 eyes of groups I/II and in 19 eyes of groups III/IV. In particular, in group III, severe vis a tergo occurred in 8 eyes. Conclusions. Intraoperative decentration, misalignment of the donor in the recipient bed, and need for additional interrupted sutures as well as high percentage of severe intraocular positive pressure were predominantly present in the femtosecond laser in keratoconus eyes. Keratoconus (KC) and Fuchs' dystrophy (Fuchs) are the leading indications for penetrating keratoplasty (PKP) . The corThe nonmechanical excimer laser trephination (Exc) has been first introduced in 1989 at the University Eye Hospital of Erlangen (Germany) . It has However, despite the promising results, the Exc PKP did not get widely spread, because corneal surgeons did not have an excimer laser in their operating theater. Instead, newer technologies were introduced, particularly femtosecond laser-assisted keratoplasty (FLAK), which got spread more widely since 2006 . HistoriThis new technique allowed creating reproducible, customized trephination patterns. The most common trephination profiles are the “mushroom” and the “top hat” profile  as well To the best of our knowledge, this is the first study to compare two nonmechanical (excimer and femtosecond laser) laser-assisted PKP in keratoconus and Fuchs dystrophy. The purpose of this work is to demonstrate the intraoperative results regarding the centration of the graft, necessity of completion of graft and donor incisions with scissors, anterior stepping, gaping, necessity of additional interrupted sutures, positive pressure during the surgery (vis a tergo), and the proper alignment of the orientation markers in host and graft.In this prospective randomized clinical single-center study, 68 patients (age 18 to 87 years) with keratoconus or Fuchs dystrophy  were randomly distributed to 4 groups: 35 eyes with keratoconus and 33 eyes with Fuchs dystrophy were treated either with excimer laser ([Exc] groups I and II) and with femtosecond laser-assisted ([FLAK] groups III and IV) penetrating keratoplasty. Exclusion criteria were repeated PKP and simultaneous cataract surgery because during the triple procedure, the iris-lens diaphragm is not stable and, therefore, might influence the main outcome measures of this study. All patients agreed to the informed consent. The study was approved from the Ethics Committee of the Saarland University, Germany.All surgical procedures were carried out by one surgeon (BS) and under general anesthesia. In the study, a 193 nm excimer laser  with a 35 Hz repetition rate and spot size of 1.2 mm, in combination with conventional donor/recipient masks, and the 60 KHz IntraLase FS Laser  have been used.Exc and FLAK were performed in patients with keratoconus and with Fuchs' endothelial dystrophy .Main intraoperative outcome measures included ultrasound pachymetry AL-3000  at the center and in 4 midperipheral points at 0°, 90°, 180°, and 270° of the donor, complications of laser trephination, trephination time, anterior gaping, graft override, need for additional interrupted sutures to achieve proper donor-host alignment, and alignment of orientation markers and positive vitreous pressure (vis a tergo) depicted in three grades . Graft decentration was measured at the end of the operation by measuring the distance between limbus and graft with calipers at the 12- and 6-o'clock position. Decentration was considered if the difference between the two distances was more than 0.5 mm. A measurement prior to incision was not possible because of the suction ring for the femtolaser which prevents view on the limbus area.Trephination was performed using the 193 nm excimer laser along metal masks with eight orientation teeth/notches. Mean patient age in keratoconus was 37.4 ± 14.2 and in Fuchs 69.8 ± 8.9 years. For donor trephination from the epithelial side using the 193 nm excimer laser MEL 70, a circular metal aperture mask . The 8 alignment incisions in both the donor and recipient were created as follows: energy of 1.5 μJ, length of 1000 μm, width of 50 μm, spot separation of 6 μm, line separation of 6 μm, and layer separation of 5 μm. The radial offsets were +2 in all recipients  and −2 in all donors .Mean patient age in keratoconus group was 40.2 ± 14.0 years and in the Fuchs group it was 69.2 ± 12.0 years. In all cases, we used energy of 0.1 μm; in the ring lamellar cut , the tangential spot separation was 5 μm and the radial spot separation was 4 μm; on the posterior side cut, the spot separation was 3 μm and the layer separation was 2 μm. The depth of the lamellar cut of the donor and recipient was 2/3 of the mean corneal thickness of the graft and recipient's eye, respectively. All diameters  were performed, 0.1 mm larger than the resulting diameter, thus overlapping each other. The donor cornea was placed into an artificial anterior chamber type Barron  to achieve trephination from the epithelial side. Each laser procedure requires a disposable glass interface, which applanates the cornea completely during the laser procedure.On the anterior side cuts, the spot separation and the layer separation were 3 For laser trephination of the recipient's cornea, the eye was fixated by means of a vacuum suction ring. The glass cone interface was placed within the suction ring so that the cornea was completely applanated. We performed a complete penetrating laser trephination after which the corneal button was removed with forceps and a spatula under microscopic control. If necessary, a microscissor was used to complete the incision. The top hat profile was used in Fuchs dystrophy, whereas the mushroom profile was used in keratoconus patients .In all patients, a peripheral iridotomy was performed at the 12-o'clock position . After tGenerally, the laser action time for trephination was much shorter for femtosecond compared to excimer laser trephination . The disStudies comparing an established corneal transplantation procedure with the new femtosecond laser technology that was introduced to clinical practice in 2006 were already carried out , 19. In A major advantage of femtosecond laser is the possibility to create different 3D profiles  (with thThe fact that FLAK created more gaps after the removal of the cardinal sutures resulted in the necessity to use more single interrupted sutures for correct donor-host adaptation. This was not due to a learning curve of the surgeon because a different cut profile was used in the FLAK group. Although, the mushroom profile has a relatively large diameter at the corneal surface, the wound apposition was less accurate. We have to admit that a suture depth of 90% can only be intended and depends strongly on the experience of the surgeon. We further have to admit that there are no ideal geometrical settings for the mushroom profile. But a more likely explanation is that in keratoconus eyes the applanation done to the cone-shaped bulging cornea results in flattening. We believe that this extreme flattening effect leads to an alteration in the theoretically planned right angles of the anterior, posterior, and lamellar side cuts. Therefore, we got instead of right angles oblique angles and instead of a round trephination an oval- or pear-shaped trephination, which led to difficulty in fitting the properly cut donor button into the somehow distorted recipient bed. In particular, in keratoconus, orientation lines of donor and recipient tended not to match exactly . In suchµm and to complete perforation in the surgery room. FLAK achieved an overwhelming number of cases with complete perforation of the cornea in comparison to the excimer PKP.It was obvious that the excimer laser needs more time to penetrate the cornea than the femtosecond laser. This is because the excimer laser digs from the surface a trench into the cornea while its energy is gradually absorbed . On the Another factor that must be considered here is the suturing technique. The double continuous running suture technique remains to be the suture of choice in FLAK . In our One of the disadvantages of FLAK is that it generates a higher intraocular pressure than the Exc PKP. This was proved by direct intravitreal measurements , 24. TheDecentration of corneal grafts in keratoconus patients with FLAK was more frequent than that in patients that were treated with excimer laser. Because of the flat applanation with the FLAK, it was more likely to obtain a decentered oval-shaped recipient incision. In contrast, in the excimer laser PKP, we have been using masks with orientation teeth which allow us to suture the first eight cardinal sutures with small risk of horizontal torsion because, according to the key-keyhole-principle, the orientation teeth in the donor fit exactly into the orientation notches of the recipient. Such a precise orientation is absent in the FLAK, since only radial markings are present. It became obvious that in the femtosecond laser trephined KC eyes these radial incision lines did not fit completely comparing donor and recipient. Therefore, the hypothesis that a better graft alignment can be achieved with FLAK cannot be confirmed with the geometrical settings in our study.Intraoperative decentration, misalignment of the donor in the recipient bed, and need for additional interrupted sutures, as well as positive pressure from the vitreous, were more frequent when FLAK was performed.Future comparative studies with a faster excimer laser platform and a concave femtosecond laser patient interface or even a “liquid interface” are needed to be carried out. These studies might show us less intraoperative complications regarding both techniques. The next step of our group is the presentation of best-spectacle corrected visual acuity, postoperative astigmatism, and regularity of topography after removal of all sutures in all eyes.


Urinary CXCL1 possessed a sensitivity of 55.81 %, specificity of 83.72 %, positive predictive value of 77.42 %, negative predictive value of 65.46 %, and an overall accuracy of 69.77 % . These results indicate that CXCL1 is elevated in BCa when compared to non-cancer subjects, but lacks robustness as a standalone urinary biomarker. Additional studies into CXCL1 may shed more light on the role of CXCL1 in BCa tumorigenesis as well as ramifications of therapeutically targeting CXCL1.Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Recently, several studies have linked CXCL1 expression to bladder cancer (BCa). In this study, we aimed to determine if increased levels of urinary CXCL1 were found in BCa patients. Voided urines from 86 subjects, cancer subjects (n = 43), non-cancer subjects (n = 43) were analyzed. The protein concentration of CXCL1 was assessed by enzyme-linked immunosorbent assay (ELISA). CXCL1 concentration level was normalized using urinary protein and urinary creatinine concentrations. We used the area under the curve of a receiver operating characteristic (AUROC) to investigate the performance of CXCL1 in detecting BCa. Mean urinary concentrations of CXCL1 were significantly higher in subjects with BCa compared to subjects without BCa (179.8 ± 371.7 pg/mg of creatinine vs. 28.2 ± 71.9 pg/mg, respectively  Chemokines are a family of small peptides that induce directed chemotaxis in nearby responsive cells. Their canonical function is immune and inflammatory reactions, such as allergic disorders, autoimmune diseases, and in viral infections. On the other hand, overexpression and uncontrolled activity of certain chemokines have been implicated in the initiation and progression of several cancers through a variety of mechanisms. Specifically, chronic exposure of cells to a chemokine-rich environment induces accumulation of macrophage and T cell, chronic activation of macrophages, abnormal angiogenesis, and DNA damage because of the presence of reactive oxygen species (Gillitzer and Goebeler One chemokine of interest is chemokine (C-X-C) ligand 1 (CXCL1), also known as growth-regulated oncogene-alpha or melanoma growth stimulatory activity, alpha. Accumulating evidence suggest that CXCL1 is overexpressed in colon, skin and breast cancers  and informed consent (IRB #Rosser 2014-1), voided urine samples and associated clinical information were prospectively collected. The urine samples were randomly collected from each subject. Urine cytology was collected at the same time as the urine samples. The study cohort consisted of 43 subjects with no previous history of urothelial carcinoma, gross hematuria, active urinary tract infection, or urolithiasis, and 43 subjects with newly diagnosed primary urothelial carcinoma. Median follow-up was 6 months. This study, which consisted of 86 subjects, adhered to PRoBE . The remaining 50 mL of urine was assigned a unique identifying number before immediate delivery and laboratory processing. The urine sample was transported to the laboratory under refrigerated conditions. Within 4 h of collection, the sample was processed in the laboratory. Each urine sample was centrifuged at 600×The level of human CXCL1  was monitored in urine samples using enzyme-linked immunosorbent assays (ELISA). Readers of this assay were blinded as to disease status. The assays were conducted according to the manufacturer’s instructions. Calibration curves were prepared using purified standards. Curve fitting was accomplished by either linear or four-parameter logistic regression following manufacturer’s instructions.The relatively constant production of creatinine, a non-enzymatic metabolite of creatine, makes urinary creatinine a useful tool for normalizing the levels of other molecules found in urine  curves were generated in which the value for sensitivity is plotted against false-positive rate (1-specificity). Areas under ROC curves were estimated and compared by Chi-square test. We defined a diagnostic test (positive vs. negative) for BCa using a cutoff threshold for CXCL1. The optimal cutoff (Youden index) was selected to maximize the sum of the sensitivity and specificity . Though the mean urinary CXCL1 concentrations were elevated in high grade vs. low-grade disease  and high-stage vs. low-stage disease , the results were not significant. ELISA data are depicted in Fig. The cohort of 86 subjects consisted of 43 subjects with active BCa and 43 control subjects. Demographic, clinical, and pathologic characteristics of both groups are illustrated in Table The ability of CXCL1 to predict the presence of BCa in voided urines was analyzed using nonparametric ROC analyses and the area under the ROC curve (AUROC), according to National Cancer Institute guidelines . However, its diagnostic capability as a standalone biomarker, sensitivity of 55.81 %, specificity of 83.72 %, positive predictive value of 77.42 %, negative predictive value of 65.46 % with an overall accuracy of 69.77 %, was less than ideal.In this current report, we describe the analysis of urinary CXCL1 in a cohort of 86 subjects using a commercial ELISA assay. Urinary protein concentration of CXCL1 was significantly associated with BCa compared to controls , has been extensively studied (Reis et al. . , Dyrskjo. (. , Lee et . (.  demonstr. (. . In this. (. , meaningUnfortunately, CXCL1 expression is not unique to BCa. Several benign inflammatory bladder disorders are noted to express and secrete higher levels of CXCL1 compared to normal bladder tissue (Tyagi et al. We recognize that our study has several limitations. First, our analyses were performed on processed, banked urines. These urines were centrifuged and separated into cellular pellet and supernatant prior to storage at −80 °C. It is feasible that freshly voided urine samples may provide different results, and it is fresh urine that would be the material used for point-of-care assays. Second, it is uncertain how the protein composition of the urine supernatant may change during frozen storage. The number of freeze–thaw cycles was kept to 1–2 by dividing the urine supernatant into multiple small aliquots. Next, we are a tertiary care facility that is preferentially referred high grade, higher stage disease, which is reflected in our cohort. Lastly, we believe that a more robust diagnostic approach would encompass a diagnostic signature composed of numerous biomarkers, as we previously published (Chen et al. We have confirmed that urinary levels of CXCL1 were elevated in a population of 43 BCa patients relative to 43 control subjects. Though CXCL1 may lack robustness as a sole diagnostic biomarker, it may be a viable therapeutic target in the future.


Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation.+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival.Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust relationship between macrophage infiltration, accompanying antigen-presentation and resulting allograft function. The availability of calcineurin inhibitors and anti-proliferative agents as well as the introduction of costimulation blockers in recent years, which prevent activation and proliferation of T-cells, has markedly lowered acute rejection episodes. Despite these improvements in immunosuppression, acute rejection still remains a significant clinical problem, particularly with respect to the growing number of marginal organs. Since even borderline rejection is linked to impairment of graft function and premature graft loss –3, acuteThe pivotal role of T-lymphocytes in the initiation of acute rejection has generally been accepted. However, there are inconsistencies regarding the role of other cell types such as macrophages: on the one hand, it has been recognized that sole T-cell infiltration and even tubulitis is not necessarily linked to impaired graft function ;6. On thMacrophages, as key elements of innate immunity, are present within transplanted kidneys contributing to acute and chronic allograft injury by a variety of mechanisms . BecauseIn organ transplantation, accumulation of macrophages was verified in models of acute as well as chronic injury. In biopsies of acute allograft rejection macrophages can account for up to 60% of infiltrating leucocytes, accumulating in different renal compartments, e.g. interstitial, perivascular and glomerular . HoweverSince current baseline immunosuppression focusses mainly on prevention of T-cell activation and proliferation, we were interested to better define the role of macrophages in kidney transplantation. First, we were interested in the extent of macrophage infiltration in subtypes of renal allograft rejection  in comparison with normal histology and chronic alteration . Secondly, we analysed macrophage infiltration into different renal compartments  according to histopathological diagnosis. In a third step we analysed outcome data of different rejection categories and correlated the severity of macrophage infiltration with creatinine values up to 36 months post-transplantation as well as with overall graft survival in an observation for more than ten years after renal transplantation. In addition to sole macrophages infiltration into the graft, we looked for properties of cell proliferation and antigen presentation expressed by infiltrating macrophages.In our transplant center, protocol biopsies are routinely performed 2 weeks and 3 months after transplantation. Additional indication biopsies at earlier time points after renal transplantation typically were performed due to allograft dysfunction, e.g. stagnating/inadequate falling creatinine. At later time points indication biopsies usually were performed to exclude acute or chronic rejection, drug toxicity or recurrence of the primary kidney disease, resp. Since 1998 all recipients of a kidney transplantation in our transplant center, except a small number of patients, who refused consent, were observed for their clinical course after transplantation. Clinical characteristics before and after transplantation, features of transplantation (i.e. donor data), course of graft function, complications etc. as well as histologic and diagnostic results were collected in a big database. Here from a total of 103 randomly chosen patients (transplanted between 2000 and 2007) and 103 corresponding formalin-fixed, paraffin-embedded renal biopsies were included in the analysis  per specimen were examined for analysis  of each biopsy as previously described . In the overall patient population with graft failure need for dialysis occurred in median after 45 months [1–170]. Patient characteristics according to the histopathological grading are presented in Having analysed acute rejecting patients below and above the median of CD68 counts we found that in the below from the median group 20/44 patients (45.45%) had no rejection, but only 14/43 patients (32.56%) in the above from the median group. 3/44 patients (12.5%) in the below from the median group had to be treated with additional ATG, due to steroid-resistant rejection, but 18/29 patients (61.1%) in the above from the median group.Focussing on the clinical outcome, biopsies with TCMR with arteritis had a significantly increased CD68 infiltration, which was reflected by significantly elevated creatinine values up to month 36 after transplantation, but no differences regarding graft survival in comparison with normal histology . In cont® as shown in Quantification of CD68 infiltration, Ki67 expression, and MHCII-HLA-DR-dependent antigen presentation was performed in biopsies according to the histopathological diagnosis by HistoquestIn a random sample of 15 biopsies with TCMR without and with arteritis we found that 79.1% ± 2.3 of MHCII-HLA-DR+ cells were also CD68+ positive, whereas 39.3% ± 8.7 of Ki67+ cells were also CD68+.+, Ki67+ and MHCII-HLA-DR+ cells was analysed manually in the peritubular, glomerular, and perivascular compartment of the different renal biopsies. On average, 27.2 tubuli, 5.3 glomerula, and 5.3 arteries were analysed per biopsy, in which the median value for tubules/biopsy was 55, 9.2 for glomerula and 10 for arteries. Severity of TCMR is transferred to the amount of CD68 infiltration in the examined renal compartments  and features of graft outcome. We found that increased macrophage infiltration—especially during TCMR with arteritis—was associated with impaired renal function up to month 36 after transplantation. However, graft survival was only limited in ABMR biopsies (p = 0.008) being accompanied by increased proteinuria 12 months after renal transplantation  (range: 0–2245 CD68 counts), we then opposed biopsies below the median of macrophage infiltration [2–83] (n = 51) to biopsies above the median of macrophage infiltration [100–2245] (n = 52). The mean value of CD68 counts in biopsies below the median was 28 ± 21. In contrast, the mean value of CD68 counts in biopsies above the median was 513 ± 538 counts (p = 5.2E-8). Comparing corresponding creatinine values until 36 months after transplantation showed that averaged creatinine values of the biopsies below the median of CD68+ infiltration (2.5 ± 1.9 mg/dl) were significantly lower than averaged creatinine values of the biopsies above the median of CD68+ infiltration  ( 1.2E-5) . Additiobetween subject effect (p = 0.044) for resulting creatinine values two week, two years and three years after transplantation. For the length of CIT only a trend (p = 0.063) was seen.Multivariate analyses (MANOVA) on magnitude of macrophages infiltration and other well known risk factors for longterm allograft function , number of MHC mismatches , delayed graft function (DGF), recurrence of primary kidney disease, peak-PRA) showed, that magnitude of macrophages infiltration had a significant impact on resulting creatinine values 2 weeks (p = 0.003), 2 years (p = 0.018) and three years (p = 0.014) after renal transplantation. Besides magnitude of macrophages infiltration only DGF had a significant thirdly performed ROC curve analysis for the resulting need for dialysis 12 and 36 months after transplantation: ROC curve analysis illustrated that there is a robust influence of the degree of CD68 infiltration (below vs above the median) for dialysis initiation 12 months  as well as 36 months after transplantation   we 5–0.848) . Multivafourthly, accounted for overall graft survival (until year 14 postTx) in biopsies below and above the median of macrophages infiltration: biopsies below the median had a significantly better graft survival than biopsies above the median of macrophages infiltration: 89 ± 36 months (median 90 [5–184]) vs 68 ± 42 months median 86 [3–131], p = 0.02)  .In contrast to the role of T-cells, knowledge on macrophages in allograft rejection is still lacking . It is gIn the present study of renal transplant biopsies the number of infiltrating macrophages correlated with the severity of acute rejection, as well as with renal function and long-term allograft function. Multivariate analysis clearly demonstrated, that besides severity of macrophages infiltration only delayed graft function (DGF) had a significant impact, in contrast to several other well-known factors for long-term renal outcome, . The importance of macrophages was independently underlined by the finding, that more severe macrophages infiltration was associated with higher rates of dialysis re-initiation 12 and 36 months after transplantation.+ cells especially into the peritubular and the perivascular compartment was linked with TCMR with arteritis. Furthermore, costaining experiments illustrated that infiltrating macrophages also displayed induced HLA-DR antigen presentation.Compartment-specific infiltration of CD68The presented data of macrophage infiltration in antibody-mediated rejection as well as in T-cell-mediated rejection from human renal transplant biopsies expands existing data on the role of macrophages as initiators of graft injury and predictors of graft outcome –24. ThisFindings on the severity of macrophage infiltration—also verified by compartmental specific examinations—being associated with the severity of TCMR are in line with previous investigations ;25–27. HGlomerular CD68 expression is regarded as a surrogate for antibody-mediated rejection, where we found only a trend for an increased CD68 infiltration. However, the detected results remain somehow contradictory: if one accounts for any CD68 positive cell within the glomeruli even biopsies with normal histology exhibit up to 70% of CD68 positive glomeruli. However, if one focusses only on glomerula with more than 3 CD68+ cells, only patients with ABMR retained positive. Additionally, to ensure the correctness of histopathological classification we analysed C4d staining of examined biopsies, which were only positive in the case of antibody-mediated rejection. Therefore combined appearances (ABMR+TCMR) as source of glomerular CD68 infiltration can be probably neglected, however, cases of C4d negative antibody-mediated rejection can´t be ruled out . DiscrepIn the current study, entire as well as compartment specific macrophage infiltration is linked to the severity of TCMR and resulting kidney function. The significance of the present results was broadened by the additional finding that macrophage infiltration was accompanied by compartment specific cell proliferation–illustrated by Ki67 expression. This may indicate that infiltrating macrophages act as an ongoing trigger of subclinical alloimmune inflammation and subsequent progression of graft injury. Recently published data by Toki et al. on the role of macrophages for the development of renal fibrosis support this hypothesis . Our datIn contrast to acute rejecting grafts biopsies from grafts with chronic damage and established interstitial fibrosis and tubular atrophy showed no induced macrophages infiltration, cell proliferation or antigen presentation. While experimental and human studies have highlighted the impact of macrophages for the development of IFTA –41, the In conclusion, using both software-based as well as compartment-specific analyses, we can clearly demonstrate that CD68 infiltration is strongly linked to acute antibody-mediated and T-cell-mediated allograft rejection. Severe TCMR with accompanying arteritis significantly affected resulting creatinine values up to 36 months after transplantation. Additional consideration of the magnitude of macrophages infiltration (below vs. above the median of CD68 infiltration) irrespective of the underlying diagnosis independently affected resulting renal function: the lower the magnitude of macrophages infiltration the better the resulting creatinine values. A result being verified by ROC curve analysis as well as corresponding graft survival more than 10 years after transplantation. The AUC for the predictive value of macrophages infiltration for emerging need for renal replacement therapy 12 and 36 months after renal transplantation were as robust as were the differences for graft survival in dependence to the magnitude of macrophage infiltration.Thus, these findings emphasize, that macrophages influx into renal allografts is an important risk factor for deterioration of renal function and a predictive indicator for rejection outcome.


The purpose of this study is to evaluate the surgical outcome after using composite grafts for secondary cleft lip nasal deformities. A retrospective cohort study of one surgeon's outcome of 35 consecutive performed secondary cleft lip nasal deformity repair. Thirty-five patients with secondary nose deformity related to unsatisfactory cleft lip repair were operated using the proposed surgical technique since 2008. All these patients met the study criterion of having anthropometric measurements performed at least one year postoperatively. Measurement of nostril size was performed at the right and left side of the nose, preoperatively and at least one year postoperatively. The study found statistically significant differences between the preoperatory and postoperatory nose measurements. In addition, we have not found statistically significant differences between the cleft and noncleft nostril sizes measured at least one year postoperatively. The findings suggest that the proposed technique is a good alternative to address secondary nose deformity related to cleft lip primary repair. Secondary alar deficiencies are a common undesirable outcome after primary unilateral cleft lip nose repair.Even when this technique has been published previously by many authors, it was not well studied and most of the articles are cases series including a few number of patients.This problem may be in relation to congenital hypoplasia or surgical technique deficiencies .Proper location of this incision would be difficult to be established in some cases.If the incision is done in a higher position, the alar nose is shortened with the consequent nose asymmetry .Different techniques have been described for alar reconstruction like local flaps and grafts.Auricular composite graft is one of the most advantageous methods because it is possible to reconstruct the structural cartilage and skin in one stage.The use of auricular composite grafts was first described by Koenig in 1902 and the use of two surfaces of skin and cartilage as composite graft was first described by Brown and Cannon in 1946 [Rettinger and O'Connell in 2002 and Ayhan et al. in 2006 described the use of composite grafts for nasal base correction in patients with cleft lip nose in a case series study observing symmetrical and functional results in a small number of patients , 4.Another case series study developed by Cho et al. in 2002  in patieThe purpose of this study is to evaluate the symmetry of the nose after using auricular composite grafts for secondary unilateral cleft lip nasal deformities.This is a prospective cohort study of one surgeon's (corresponding author) outcome of 35 consecutive secondary unilateral cleft lip nasal deformity repair from the Outreach Surgical Center Program Lima Peru.previously alveolar bone graft during mixed dentition period,vestibular nose lengthening (composite V-Y method) ,medial mobilization of the lateral alar crus (composite V-Y method),shortening of the nasal base width (when necessary),septoplasty.These patients had an open rhinoplasty and the following associated procedures based on Millard Jr. principles :previousAll these patients met the study criterion of having anthropometric measurements performed preoperatively and at least one year postoperatively.nostril dome height, which was measured from the midway point at the base of the columella to the highest point on the nasal dome;nostril apex height, which was measured from the midway point at the base of the columella to the highest point of the nostril;alar width, which was measured from the midway point at the base of the columella to the most lateral point of the nostril in a line perpendicular to the axis of the columella;alar length, measured from the alar columellar junction to the alar base.These were the standard anthropometric measurements :nostril Measurements were performed at the right and left side of the nose, preoperatively and at least one year postoperatively.These measurements were compared in order to determine pre- and postoperatively nose symmetry.Outcomes were additionally determined by a parent questionnaire assessment.Differences in alar length were identified in these patients in order to evaluate the amount of tissue necessary for alar reconstruction.The tissue's requirement is estimated using the length of the alar nose measured from the alar-columellar junction to the alar base.Based on our experience, the graft is designed 50% larger than the estimated defect due to the scar contracture of the graft observed during the healing process.In order to maximize graft survival, careful preoperative design, preparation of the recipient site, meticulous surgical technique, and diligent postoperatory care are mandatory.The recipient bed of the graft located at the deficient alar base must be in good condition for proper development of the process of plasmatic imbibition, vascular inosculation, and neovascularization.All the scar tissue should be excised from the recipient site leaving a healthy raw surface to receive the auricular composite graft. The use of electrocautery should be avoided as possible.After design with marking pen of the required auricular tissue in the ear, local anesthetic without epinephrine is injected around the designed composite graft avoiding any hydrodissection of the skin off the cartilage .The skin and cartilage are incised in one block with 15C blade following the skin markings.The size of the cartilage component should be a few millimeters bigger than the skin component in order to guarantee their integrity as composite graft .The graft should be harvested carefully and manipulated gently grabbing the cartilage and skin with the forceps simultaneously. Any skin traction alone may separate it from the cartilage losing the tissue connection between them.After this, carefully edge to edge closure is performed at the donor site using skin stitches.Up to 1.5 centimeter defect can be closed primarily without problems. Larger grafts are rarely required for secondary alar nose repair in these patients.Long term appearance of the donor site is acceptable .The affected alar nose is incised at the level of the scar and this scar tissue should be removed carefully leaving healthy tissue at the borders to receive the composite graft and guarantee its survival. Use of cautery should be avoided as possible.The skin edges of the auricular composite graft are directly closed to the defect's skin edges with simple resorbable sutures.The composite graft is located between the alar nose and upper lip suturing the skin component only using resorbable simple stitches.Stitches are placed first at the corners  and between the graft and alar nose and upper lip, making easier the application of the following sutures. These stitches should not include the cartilage component and must be placed superficially in order to avoid any bad alignment between the borders.Special attention must be taken with the sutures located around the medial surface of the graft where the skin is firmly attached to the cartilage. At this level the stitches should include only the skin avoiding any disruption between the component's graft.Antibiotic ointment is applied to the surgical surfaces.Moisturizing ointment is recommended to be applied over the graft during one week in order to avoid graft desiccation (greatest risk for graft failure).Appearance of the grafts is not good during the first days becoming first blue and then pink after epidermolysis. Complete survival was confirmed after 7 days.We did not use any drug to improve graft survival in the studied group.P < 0.05 yielded a confidence level of 95%.A two-sample test of proportions was performed to assess the statistical significance between the two methods. The data were analyzed using Stata 11.0 software.Thirty-five patients with secondary alar nose deformity related to unsatisfactory unilateral cleft lip repair were operated using the proposed surgical technique since 2008. Gender: men 24 (68.57%) and women 14 (31.43%). Side: left 23 (65.71%) and right 12 (34.29%)The mean age at the time of the surgery was 11.57 years (range 8 to 14 years).The preoperatively mean height and width of auricular composite tissue were 16.21 mm (range: 18 to 13 mm) and 10.35 mm (range: 13 to 8 mm), respectively.We observed statistically significant preoperatory differences between the cleft and noncleft sides and between the preoperatory and postoperatory nose measurements Tables to 3.In addition, we have not found statistically significant differences between the cleft and noncleft sides measured at least one year postoperatively .Observed rate of graft survival was 100% with 2 partial necroses.90.35% of the patients were very satisfied with the surgical outcomes.Three patients (8.5%) showed fair results with some recurrence of the asymmetry of both nostrils.Surgical outcomes are presented in Tables Surgical repair of the nasal deformity caused by trauma, tumor extirpation, burns, and cleft lip nose is challenging because it requires reconstruction of the outer and inner skin and supporting cartilage –5, 8–12.The auricular composite graft let us reconstruct the three-layered structure of the alar and has a similar shape, curve, color, and texture. In addition, the graft is similar to the recipient site because the ear has components with various shapes and curves.Primary closure of the donor site can be achieved for a defect less than 15 mm as described by Singh and Bartlett in 2007  Figures and 5.In case of secondary cleft lip nasal deformity with severe tissue deficiency, auricular composite graft can be useful for columellar lengthening or for creating symmetrical nostrils –12.The main disadvantage of this method is the contracture of the graft after the healing process which has been observed in all cases.Difference between pre- and postoperative width of the graft was 5.27 mm and represents 50.91% of the initial width of the graft (10.35 mm).This percentage represents the contracture of the graft and supports our preoperatory design considering a composite graft 50% larger than the estimated defect.This outcome is similar to the initial report made by Rees  with 53%Grafted tissues frequently shrink their width and thickness. In order to improve this situation, we design the composite grafts larger than the estimated defect preoperatively.Cosmetic appearance of the graft is difficult to be improved and this is the main limitation of this technique.In relation with the size of the graft, initial studies concluded that a graft larger than 10 mm results in subsequent necrosis of the graft , 15.However, we use larger grafts (mean 20 × 12 mm) with high rate of survival (85.71%).Parkhouse and Evans  reportedPrevious anthropometric studies described by Farkas et al.  did not This is the reason why these variables are not affecting our results and any stratification was not necessary in the studied group.Many papers have been published about the use of auricular composite graft in aesthetic and reconstructive surgery.Most of them are case series studies including a small number of patients.This is the first analytic research to evaluate objectively differences between the cleft and noncleft side of the nose pre- and postoperatively.Objective evaluation of the cleft nose deformity after using conventional Millard's technique for primary repair has been done and nostril apex height, alar length, and width asymmetry have been determined in all the cases preoperatively .Effectiveness of the proposed technique for secondary nose deformity repair has been confirmed with this comparative study observing nonstatistical significant differences between the cleft and noncleft side and statistical significant differences between pre- and postoperatively anthropometric nose measurements Tables  and 3 Fto 13.We observe some small differences between the cleft and noncleft side in the presented cases; however, they are small and nonstatistically significant. These differences are mainly related to the recurrence of the septal deviation.P: 0.14)  .Nasal retainers are commonly used in cleft nose deformity repair; however, we did not use any molding device in this study due to the observed complications related to their use, like skin reaction, infection, ulceration, recurrence, pain, and others.This problem requires additional studies to evaluate cosmetic appearance of the graft.The proposed technique of open rhinoplasty in combination with auricular composite grafts has been useful for gaining additional alar length in patients who otherwise have a satisfactory relationship between the anatomic subunits.The findings suggest that the proposed technique is a good alternative to address secondary nose deformity related to unilateral cleft lip primary repair.


It provides most of the calories in the human diet and, as a bulk commodity, it is used across broad industry sectors. Starch synthesis and degradation are not fully understood, owing to challenging biochemistry at the liquid/solid interface and relatively limited knowledge about the nature and control of starch degradation in plants. Increased societal and commercial demand for enhanced yield and quality in starch crops requires a better understanding of starch metabolism as a whole. Here we review recent advances in understanding the roles of carbohydrate-active enzymes in starch degradation in cereal grains through complementary chemical and molecular genetics. These approaches have allowed us to start dissecting aspects of starch degradation and the interplay with cell-wall polysaccharide hydrolysis during germination. With a view to improving and diversifying the properties and uses of cereal grains, it is possible that starch degradation may be amenable to manipulation through genetic or chemical intervention at the level of cell wall metabolism, rather than simply in the starch degradation pathway  Starch, a glucose polymer, is of enormous biological and commercial importance. Starch, in roots, tubers and seeds, provides a carbon store for use by the plant during times when photosynthesis is not possible, such as regrowth following winter dormancy and during seed germination –5. StarcStarch degradation during grain germination is also of great societal and commercial importance, but has attracted less recent research. The success with which new generations of plants are established following germination and the vigour of the seedlings are largely determined by the interplay between an intricate developmental programme, genetically encoded and the supply to the growing embryo of energy from degradation of starch and other reserves in the seed ,7. The cMolecular genetics in model species has provided significant insight into the enzymology and the regulation of starch degradation; however, studies of model plants alone are unlikely to provide sufficient information for crop improvement ,2. Here D-glucose, amylopectin  and amylose   and lesser amounts of cellulose and other polysaccharides [One process that may be indirectly important for starch mobilization is cell wall degradation. The cereal endosperm C is a nocharides ,36. It icharides . Earliercharides . The patcharides ,38. DespD-xylan xylanohydrolases  which cleave the (1→4)-β-xylopyranosyl backbone of AX and AX arabinofuranohydrolases  that release L-Araf from the xylan backbone and also hydrolyse linkages between two arabinose residues. In addition, the exo-enzymes α-L-arabinofuranosidase and β-D-xylosidase also contribute to AX digestion by releasing terminal residues from oligosaccharides [To dissect the link between cell wall integrity and starch degradation, we undertook a chemical genetics approach focused on the hydrolysis of AX polymers. AX degradation to its constituent monosaccharides is mediated through the action of endo-1,4-β-charides –43.We found that particular iminosugars directly inhibit enzymes of AX degradation. When applied to germinating barley grains, they retard a wave-like spread of AX degradation through the endosperm and also retard starch loss over the same period (result to appear elsewhere). These findings strongly suggest that diffusion of macromolecules is restricted by endosperm cell walls; cell wall degradation is therefore required for normal rates of starch mobilization to occur. Our research provides new routes for genetic or chemical modulation of both the rate of cell wall mobilization and the rate of starch loss in the endosperm, with potential applications in the improvement of seedling vigour and the use of grains for ethanol production in the brewing and biofuel industries.Arabidopsis seedlings . This suggests that the inhibitors interfere with essential growth processes in the root common across plant species. Inhibition of root growth is not solely the consequence of slower mobilization of endosperm reserves and thus reduced availability of sugars for seedling growth [Arabidopsis, α-L-arabinofuranosidases  are expressed in the root vasculature, in emerging lateral roots and in primary and secondary xylem in roots of adult plants [Arabidopsis, loss of glucosidase I in the gcs1 mutant leads to embryo developmental arrest [rsw3 Arabidopsis mutant plants lacking glucosidase II α-subunit show radial root swelling, poor seedling development and a range of pleiotropic effects [The inhibition of barley root growth by iminosugars such as DNJ A is alsog growth . DNJ alst plants ,45. Imint plants . Both gll arrest . In addi effects ,49.We have highlighted recent advances in our understanding of starch degradation and cereal endosperm metabolism achieved through chemical genetics approaches. Our work provides new insights into endosperm metabolism and thus facilitates identification of new targets for informed breeding programmes aimed at cereal grain improvement for biotechnological applications and enhanced crop establishment and vigour in the field. The promiscuity of iminosugars (e.g. DNJ) ,27,32 co


International Journal of Mental Health Systems would like to thank all our reviewers who have made an indispensible contribution to the journal in Volume 9 (2015).With the proliferation of journals and the ever-increasing demands on the time and expertise of reviewers it has become increasingly difficult for editors to get high quality and timely reviews. On behalf of authors as well as the Journal the editors of  Helal Uddin AhmedBangladeshQais AlemiUSAGjumrakch AlievUSAPeter AllebeckSwedenNoor AmawiUSAGregory ArmstrongAustraliaJoseph AsareGhanaCecilia AslundSwedenMichelle BanfieldAustraliaConcepción BarrioUSAPeter BartlettUKCarolina BorgesBrazilLisa BossUSADavid BurkeAustraliaMeena Cabral de MelloSwitzerlandJosé Miguel Caldas de AlmeidaPortugalMaureen CanavanUSAÖnver CetrezSwedenSudipto ChatterjeeIndiaRie ChibaJapanAlex CohenUKJudith CohenUSAErminia ColucciAustraliaAnnette CrisantiUSAWendy CrossAustraliaJoachim DiederichAustraliaElizabeth DinapoliUSAMichael DunneAustraliaVivian DzokotoUSAJulian EatonUKAlberto FergusonColombiaDeede GammonNorwayEshetu GirmaEthiopiaDaniela Goncalves BradleyUKEnrique GraciaSpainMargaret GriggAustraliaOye GurejeNigeriaTeresa HallAustraliaNutmeg HallettUKLaura HartAustraliaEdvard HauffNorwayAshraf HosseiniAustraliaAsma HumayunPakistanAbdallah IbrahimGhanaPetru IfteniRomaniaAfzal JavedUKMichael JonesAustraliaAnthony JormAustraliaRitsuko KakumaAustraliaHarry KennedyIrelandSusan KiddAustraliaJohn KjøbliNorwayManami KodakaJapanBrandon KohrtUSAJanice KopinakCanadaIrene KretchyGhanaNhan LaAustraliaTero LaihoFinlandYik-Wa LawHong KongLars LienNorwayElizabeth LinCanadaLijun LiuChinaWeishu LiuChinaAnthony MannarinoUSANiall McCraeUKPeter McGovernSwitzerlandGraham MeadowsAustraliaGlenn MelvinAustraliaDamian MohanIrelandMervyn MorrisUKLaura K. MurrayUSADavid NdeteiKenyaSudan NeupaneNorwayThi Mai Hien NguyenViet NamAngela NickersonAustraliaAnne Marie O’KeefeUSAKwaku Oppong AsanteGhanaClaire O’ReillyAustraliaJong-Ik Park Democratic People’s Republic of KoreaSidandi PaulBotswanaVeikko Pelto-PiriSwedenInge PetersenSouth AfricaMichael PhillipsChinaAsheq RahmanAustraliaCarla RashUSAPaula ReaveyUKRusty ReevesUSASiobhan ReillyUKHeather RobinsonUKDyann RossAustraliaAlison SalloumUSADyaa SaymahUKNasima SelimBangladeshAkihiro ShiinaJapanSiham SikanderPakistanPeter SilverstoneCanadaWilliam SledgeUSADayanandan SomasundaramSri LankaRobert StewartMalawiRupert SucklingUKLong SunChinaCarlos Suso-RiberaSpainNora SveaassNorwayTheonie TacticosAustraliaHwang Tae-YeonRepublic Of KoreaLeslie TerryAustraliaMurali ThylothIndiaJane Topolovec-VranicUSAAthena TsaiTaiwanSonsoles Valdivia-SalasSpainMark Van OmmerenSwitzerlandBregje Van SpijkerAustraliaRuth Benedicte VeenhuizenNetherlandsTua Vinther-JensenDenmarkWei Chun WangAustraliaXingmin WangChinaLaura WhiteUSAHarvey WhitefordAustraliaMirkuzie WoldieEthiopiaAlexandra WrightAustraliaFu YangChina


Cardiovascular Journal of Africa and believe it appropriate in this first issue in which I am involved to pay tribute to my predecessors, to acknowledge my previous error and express my hope that I can continue the traditions of the Journal.I am delighted to have been appointed Editor-in-Chief of the When the late Professor Andries Brink approached me as a newly appointed head of Cardiology at the University of Cape Town and Groote Schuur Hospital in the late 1980s with his innovative proposal for a uniquely South African cardiology journal, I was not enthusiastic. I responded with youthful arrogance and ignorance that ‘there were more than enough journals and we did not need another one’. How wrong that was!Cardiovascular Journal of South Africa and under his guidance and rigorous scholarship it became established and recognised as a repository for publications of quality, initially mainly from South Africa, but with increasing numbers from other countries. When Professor Andries Brink passed away, his son Professor Paul Brink single-handedly continued to edit and direct the Journal. I consider that the highpoint of its 25-year growth trajectory was the acceptance of the Journal as the official journal of the Pan-African Society of Cardiology (PASCAR) and its change of name to the current one of the Cardiovascular Journal of Africa.Professor Andries Brink forged ahead, despite widespread scepticism, founded the In 2014 it is difficult for those who did not personally experience the events of the decades prior to 1994 to understand or appreciate exactly how important the changes and developments post 1994 have been. In the 1980s, academic, clinical and scientific contact between South African cardiologists and our colleagues in most of the rest of Africa was negligible. South Africans faced academic boycotts from countries both within and without Africa. Travel to African countries for South Africans was extraordinarily difficult and it was equally difficult, if not more so, for colleagues from other African countries to visit South Africa. How wonderful to have experienced how things have changed for the better!Today there is vigorous interchange and interaction, with collegial participation at continental meetings, exchanges of trainees, and a generous willingness to share expertise throughout the continent. Very importantly, multicentre co-operative research into the diseases of Africa has been instituted, and hopefully in the near future, new insights facilitating the management of patients with diseases that are common in Africa will become available. Other multicentre epidemiological investigations and registries on the impact of conditions not previously investigated in depth in Africa, such as coronary artery disease and atrial fibrillation, have been remarkably successful. The Journal has been involved directly or indirectly in much of this.The two Professors Brink, Andries and Paul, deserve recognition for their major contributions to clinical medicine, cardiology and cardiovascular science, but very importantly also, for their role in helping to develop and grow a continental publishing initiative that is enhancing patient care, medical training, and cardiovascular research in Africa.In this editorial I have tried to highlight some items of particular interest to me in the current issue. This is not comprehensive and inevitably driven by personal preference.Many states in Africa lack reliable information on health and illness issues, which would allow planners to allocate scarce resources to areas of need, and healthcare practitioners to examine and improve outputs. There are new and very helpful efforts to correct this problem. In this issue Bonny and colleagues (page 176) provide an overview of sudden cardiac death in Africa and an ambitious proposal to collect reliable information. Chin (page 151) provides an editorial comment summarising the problem and potential solutions. The outcome of the project will be eagerly awaited. In a similar vein, Brun and colleagues (page 159) examine a large number of patients at risk of venous thromboembolism and demonstrate under-use of recommended prophylactic anticoagulation. These two initiatives are both multicentre studies involving sites from many different African countries and it is heartening to see such co-operation, which can only bode well for the future.In a prospective cohort study, Borkum and co-workers (page 153) examined ambulatory blood pressure and renal function in asymptomatic HIV-positive patients. The prevalence of chronic kidney disease was lower than anticipated and HIV infection was associated with an ambulatory non-dipping status, which suggests an underlying dysregulation of the cardiovascular system. In the short term, anti-retroviral therapy did not seem to improve loss of circadian rhythm. A non-dipping pattern is an established entity with clinical implications, and is associated with higher cardiovascular morbidity and mortality rates. The high prevalence of non-dippers in the HIV-infected group in this study supports data from other countries. How this non-dipping pattern will impact on long-term mortality and morbidity in HIV-positive patients remains to be established.With the increasing and widespread use of new imaging modalities, we are learning more about cardiac function and involvement in systemic diseases. An article from Turkey (page 168) describes echocardiographic abnormalities in patients with rheumatoid arthritis and the influence of treatment on those abnormalities. Interestingly for me, the old-fashioned but evergreen ECG also reflected some of the changes. Cardiac imaging is further highlighted in a review of cardiac magnetic resonance imaging by Scholtz and others (page 185). This reports the clinical utility of this exciting modality.The letter from Schamroth (page 192) regarding the adverse effects of the Noakes diet on lipids is of considerable interest and concern, given several such anecdotal verbal reports from colleagues around South Africa.


One of the commonest queries I receive as Editor-in-Chief is whether a submission can be accepted when the author’s message is already known. The paper may have been presented at meetings a couple of times and might even have appeared in abstract form. Can we, as a journal, go ahead and publish without eyebrows being raised and the accusation of duplicate publication being made?New England Journal of Medicine. You may have heard of him, although on the other hand you may not.The story starts with a classic of the editing world. His name was Franz Ingelfinger, a German-American, and for 9 years (1967–76) he was the Editor of the Ingelfinger , in 1969I can see the pressure, of course. Journals take time to reach a decision, so why not submit the same paper to two, three, maybe four or five journals simultaneously? After all, is that not what creative authors do in the big, bad world of mass-market writing? Then before you know it, two of your identical submissions are accepted, one some months after the other and … bingo! … you have entered the ranks of the duplicate publishing author.Or, you may be a particularly prolific author and have forgotten that one of your team submitted a paper on a specific topic 2 years earlier. It may have been published in some lesser-known journal and may even have passed you by. It happens. A subsequent trainee has a go, unaware of his predecessor’s actions and out comes that second paper. Again, unwittingly you have become a duplicate author and it is not a happy place to be.They waste finite resources. Journals have a limited number of pages available and duplicate submissions will be reviewed twice, indexed twice, copyedited twice, distributed twice and so on.They overload available medical information. It simply takes longer to find what you need.They overemphasize the findings. The classic is a meta-analysis looking at the antiemetic efficacy of ondansetron . This shDuplicate publications contravene copyright law, if you have signed your copyright across to another journal. This is less of a problem these days with Open Access, where the requirement for an author to hand over copyright is becoming rare.Anyway, why should a journal worry? Why should anyone be concerned? After all, each of us seeks to disseminate our work as widely and as rapidly as we can. Yet the publishing dilemma is clear because duplicate publications can cause trouble for a number of reasons :They waLanguage bias is also an issue, especially for an international journal and certainly when it comes to the influence on meta-analyses. One study  assessedJournal of Bone and Joint Surgery (Br) a study of so-called original articles in that journal showed one in 13 to be duplicate or fragmented publications [The Anglo-German study may be exceptional but the problem is manifestly global. In the former ications . Fragmenications  looked sOn Medline presently, there sit 22 million references  to journSo what are the rules of the game? These are well described by the International Committee of Medical Journal Editors (ICMJE) and followed by many . The guiTwo things are very clear, however. First, submitting the same paper to two journals simultaneously is a non-starter. Second, if your submission is very similar to work reported elsewhere then (i) reference that work and (ii) say so in your letter of submission. However, if your work has appeared as a presentation or abstract before, that does not matter, but do reference it anyway.JHPS, but duplicate publication is certainly a topic about which I am asked repeatedly by potential authors. That need for us each to publish frequently and widely seems insatiable. So please have a read of the ICMJE guidelines [Of course, none of what I have written here is applicable to idelines  and, if JHPS and its content, which in many respects is why I am here, what specifically grabbed my attention in the last issue (2.2)? Naturally every paper we publish has done well to appear on our pages and each has added its own aliquot of information to the ever-expanding field of hip preservation surgery. However, I was especially caught by Kalisvaart and Safran’s [Now turning to Safran’s  review oSafran’s , put togAnd for this issue? Issue 2.3? Oh boy, things are beginning to take off at such a pace and in a way that I for one never expected so early in the life of a fledgling journal. Downloads are skyrocketing and our submission inbox always, always, always contains something interesting. Actually, everything sent in is interesting. Why, oh why can we not publish the lot?It is our reviewers, you see. They have an eye for the uncanny, the worthwhile, the message we can all take home. They are a tremendous lot and deserve the largest vote of thanks any editor can give.et al.[So when you look at issue 2.3 do be sure to read everything, although I confess to lingering a little longer over two papers in particular. The first was the excellent review by Bardakos  on all tet al. on hip aMy very best wishes to you all.


One of  journal  to suppo journal . For exa journal . HoweverMore generally, we believe that our trial supports the use of amphotericin B plus flucytosine in populations with severe disease, as frequently seen in resource-limited settings, and we were pleased to read that the authors also endorse advocacy efforts to increase the availability of flucytosine in such settings. Although the presented network meta-analysis provides valuable aggregate evidence, it is our opinion that the evidence is not sufficiently strong to override the conclusions from our large and well designed trial, given the limitations cited by the authors regarding substantial heterogeneity between the included study populations, small sample sizes of many of the included studies, the inclusion of nonrandomized studies, and well recognized issues related to indirect comparisons . However


Repairing mandibular body fractures presents unique challenges not encountered when repairing long bones. Large tooth roots and the presence of the inferior alveolar neurovascular bundle limit safe placement for many types of orthopedic implants. Use of non-invasive fracture repair methods have increasingly become popular and have proven safe and effective at achieving bone healing. Non-invasive fixation constructs have not been tested in dogs using cantilevered bending. Furthermore, non-invasive fracture repair constructs have not been tested at the location of a common fracture location – the mandibular first molar tooth (M1). The objectives of this study were to test the strength and stiffness of three non-invasive mandibular fracture repair constructs and to characterize the impact that tooth crown preservation has on fixation strength for fractures occurring at the M1 location. Specimens were assigned to three treatment groups: (1) composite only, (2) interdental wiring and composite (IWC), and (3) transmucosal fixation screw and composite. For each pair of mandibles, one mandible received crown amputation at the alveolar margin to simulate the effect of crown loss on fixation strength and stiffness. Regardless of the status of crown presence, IWC demonstrated the greatest bending stiffness and load to failure. With the crown removed, IWC was significantly stronger compared to other treatments. All fixation constructs were stiffer when the tooth crown was preserved. In fractures at this location, retaining the tooth crown of M1 significantly increases stiffness of interdental wiring with composite and transmucosal screw with composite constructs. If the crown of M1 was removed, IWC was significantly stronger than the other two forms of fixation. Mandibular fractures are the most commonly occurring maxillofacial fractures in veterinary patients –3. LopesNon-invasive fracture repair techniques do not require surgical exposure of the fracture site and minimize risk of damaging or disrupting anatomic structures such as tooth roots or vessels. Non-invasive techniques have gained popularity due to extensive experience with clinical application of dental composites in veterinary medicine –11. The Teeth suffering periodontitis or endodontic disease prior to fracture have previously been recommended to be extracted . FrequenThe purposes of this study were twofold: (1) to compare the strength and stiffness between three non-invasive mandibular fracture fixation constructs using cantilevered bending and (2) to compare the impact on strength and stiffness that retention of the crown of M1 had on the three non-invasive fixation techniques.The mandibles from 32 deceased Beagle dogs with adult dentition (>8 months of age) were obtained for this study. All mandibles were grossly examined for complete dentition and normal tooth morphology extending from the canine through the third molar teeth. Periodontal probing was performed and intraoral dental radiographsPaired specimens were randomly assigned to one of three treatment groups: composite only (CO), transmucosal screw/composite (TSC), or interdental wiring/composite (IWC). Within each treatment group, specimens were randomly assigned to a group designated for removal of the crown of M1 to simulate the effect that tooth crown removal may have on mechanical properties of fixation. Eight paired specimens were designated as controls (CNTL) and were randomly assigned to have one mandible of each pair to undergo removal of M1.Specimens were frozen (−20°C) until fixation and biomechanical testing. All mandibles underwent a maximum of one freeze–thaw cycle. No specimens were frozen following dental scaling and polishing. Whenever thawed, specimens were wrapped with wet paper towels to maintain hydration.An osteotomy was created mesial to M1 and perpendicular to the long axis of the mandibular body on all specimens except CNTL. A surgical oscillating saw,At the time of fixation application, mesial and distal segments were stabilized using a 2″ C-clamp placed over the osteotomy site. The interdental wiring treatment (IWC) received a Stout loop-wiring pattern  using 24For all treatments, the crowns of all teeth extending from the first premolar through third molar were etched for 20 s with 38% phosphoric acidSpecimen weight, time of application of fixation steps, and fixation weight were recorded. For consistency, a single investigator (CL) performed IWC application. The ramus of each specimen was embedded in a self-curing methacrylate acrylicTesting of the structural stiffness and load–displacement behavior was measured using a servohydraulic testing systemSpecimens were loaded into the testing jig and force was applied to the canine tooth cusp tip. A 1000 lb load cell was used to record the applied force. Force was applied at a speed of 10 mm/min. The distance from the jig to the point of force application was recorded in order to calculate the moment arm.Failure was defined as the point at which cohesive failure (construct breakage) or adhesive failure (construct separation from tooth structure) occurred Figures A,B. For Graphs were plotted of the acquired data from the load cell and the ram displacement (millimeter), displaying load (Newton) vs. displacement (millimeter). Ultimate strength was defined as the point at which the structure was under maximal load. Stiffness was calculated by determining the slope of the linear segment of the load–displacement curve (Newton per millimeter). The type of failure – cohesive, adhesive, or tissue- was noted for all specimens.p ≤ 0.05 for significance). Robust rank-based linear mixed models were fit using a sandwich estimator to estimate SE . Time of composite application was consistent between treatments. Time of IWC application did not vary regardless of the tooth crown group; however, overall time taken to apply fixation of the IWC treatment was greater than the time required for TSC treatment (2.5× greater for crown removed and 2.8× greater for crown present groups). Specimen age and weight were recorded  and did not vary between treatments.Ultimate failure load was determined by bone fracture for CNTL mandibles. One control mandible did not register an ultimate failure load point due to the specimen exceeding the displacement and load limits of the test setup. Ultimate failure load for all treatments was defined as the point of greatest load before failure. Several treated specimens’ results registered a slight decrease in load before experiencing ultimate failure. All specimens contained a significant linear segment enabling stiffness calculation as the slope of the best-fit line Figure . CohesivThe impact of the presence or absence of M1 on ultimate strength and stiffness were evaluated for each treatment. Comparison within treatments was demonstrated using a HLE to demonstrate treatment interaction Figure . An intep = 0.38, CO p = 0.16, TSC p = 0.73). Treatment comparisons of means within crown groups provide direct measure of the relative impact crown presence has on different pairs of fixation. When the crown of M1 is present, the ultimate strength compared between fixation techniques was not different . In the crown removed groups, IWC was shown to be significantly stronger than both CO (p = 0.014) and TSC (p = 0.034) treatments. Although not statistically significantly different, the mean ultimate strength of the CO treatment and that of the TSC treatment were greater when the crown was intact .To estimate the effect of the loss of crown structure, contrasts based on a mixed model analysis were used Table . Resultsp = 0.03) and TSC (p = 0.002) treatments (Table When comparing stiffness using an estimation of means (HLE), an overall trend existed demonstrating that the crown removal groups were less stiff for each treatment Figure . Stiffne p = 0.00 treatmenp = 0.003) on stiffness across all treatments when comparing an estimate of means  spanned by composite results in increased construct stiffness and resistance to bending. Removal of the tooth crown resulted in the greatest reduction in the mean stiffness of the IWC construct. The structural stiffness of a material is directly affected by the thickness of that material . An atteWhen testing with four-point bending, acrylic splints incorporating Erich arch bar interdental wiring technique showed an increased ultimate strength and stiffness compared to acrylic splints used with or without other wiring techniques (Stout Loop) . In thatDirect bone healing  occurs in the presence of anatomic fracture reduction and rigid fixation . MaintaiOur results show that when M1 crowns were removed, the IWC construct was significantly stronger compared to CO and TSC constructs. Therefore, in clinical situations where the crown of M1 must be removed, the strongest anticipated construct tested will be IWC. It is unknown how predictable removal of an entire tooth root has on testing since root extraction creates an inherent instability in the reduction of the fracture fragments. Further investigation in this area may help discern how various dental treatment options may impact fixation strength for fractures occurring at this location.p = 0.003). Maintaining the tooth crown may be clinically relevant for the optimization of bone healing through a stiffer construct’s ability to minimize micromotion.An interaction was evident in both strength and stiffness when comparing estimates within crown status groups. Mean ultimate strengths decreased in the CO and TSC treatment groups when the crown was not present but mean ultimate strength increased in the IWC treatment group. The wire’s contribution to ultimate strength is greatest in the IWC construct when the tooth crown is missing. When comparing the effect of crown status on stiffness, IWC and TSC were significantly stiffer when the crown was present. Further studies are needed to determine exactly how the wire of the IWC and TSC treatments may contribute to the stiffness. Removal of the crown of M1 resulted in increased ultimate strength but decreased stiffness for IWC. Under this condition, the wire’s contribution to construct strength is greater than the absence of the tooth crown decreasing construct stiffness. The specific relationship between the wire and composite, and contribution to ultimate strength is likely dynamic and was not investigated in this study. Regardless of treatment selected, stiffness of each repair should be expected to decrease with removal of the tooth crown. Interaction was likely unapparent in the graph due to the strong difference in stiffness of IWC, and TSC between crown status groups. This is further evidenced by the significant effect of crown status on stiffness when estimated across all treatments , the use of transmucosal screws could be a time-saving measure and decrease the risk for wire sticks to the patient and the surgeon during application.In vivo, stabilization of the rostral mandible by the contralateral mandible and the pull by musculature in the intermandibular space will increase or decrease buccolingual stabilization depending on obliquity of the fracture. Of the constructs tested here, we believe that TSC fixation would be best at counteracting any forces of distraction that may result in the buccal cortical gapping as a result of the pull by the intermandibular muscles.Transmucosal screw and composite fixation did not show equivalent ultimate strength to IWC fixation in this study. TSC fixation may still offer a beneficial clinical application in edentulous patients or those with advanced periodontal disease lacking healthy available anchorage teeth. In cases where a significant loss of dental tissue exists with which to secure an interdental wire, the IMF screw could be a useful tool through which stabilization of the fracture can be achieved. A larger sample size may have shown a difference in ultimate strength for the CO treatment group based on crown presence. This is relevant since clinical situations exist where practitioners lack time or expertise to effectively place interdental wire fixation. In clinical situations where CO treatment is the sole form of fixation applied, efforts should be made to preserve the tooth crown of M1 provided it will not compromise healing.The Stout multiple loop wiring technique provides the benefit of anchoring the wire around multiple teeth on either side of the fracture. Neither clinical nor research investigations have evaluated the impact that the number of teeth incorporated into an interdental wiring technique has on stabilization. Experimental use of bovine rib as a model for mandibular fracture repair demonstrated no significant resistance to breakage existed with greater than three screws in each fracture fragment . It is uWhen confronted with mandibular fracture repair involving M1, careful consideration should be given to which repair techniques can be applied and the impact that removing the tooth may have on that repair. IWC constructs demonstrate significantly greater strength compared to CO or TSC when the crown of M1 is removed. Maintaining M1 significantly increases stiffness in the IWC and TSC constructs and likely is associated with the composite spanning shorter distances between anchor teeth. Fixation devices with greater ultimate strength and stiffness are expected to reduce micromotion. The increased rigidity of the construct resultant from the preservation of the crown of M1 is expected to facilitate a stronger construct that would improve conditions conducive to primary bone healing. The use of transmucosal screws and ligature wire with composite appears to offer no increases in fixation strength or stiffness compared to the other tested fixation techniques. It is unknown how the application of transmucosal screws and ligature wire with composite may enhance stabilization of non-invasive fixation devices in edentulous patients or patients with oligodontia.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.http://journal.frontiersin.org/article/10.3389/fvets.2015.00018The Supplementary Material for this article can be found online at Click here for additional data file.Click here for additional data file.


In orthopaedic and trauma surgery, the rapid evolution of biomedical research has fundamentally changed the perception of the musculoskeletal system. Here, the rigor of basic science and the art of musculoskeletal surgery have come together to create a new discipline -experimental orthopaedics- that holds great promise for the causative cure of many orthopaedic conditions. The Journal of Experimental Orthopaedics intends to bridge the gap between orthopaedic basic science and clinical relevance, to allow for a fruitful clinical translation of excellent and important investigations in the field of the entire musculoskeletal system. The essence of life science is to systematically describe the way organisms live. In the orthopaedic field, the rapid evolution of biomedical research during the past 30 years has changed fundamentally the way we think about the musculoskeletal system in health and disease. For example, while menisci were once thought to be functionless remnants of intra-articular leg muscles , it is nJournal of Experimental Orthopaedics – the board of ESSKA, the European Society of Sports Traumatology, Knee Surgery and Arthroscopy – recognized the need to establish a scientific journal that would publish basic science reports of new and important investigations in the field of the entire musculoskeletal system with a view of translating them into clinical reality. ESSKA hosts bi-annual congresses, with an ever-growing number of participants and presentations of high scientific quality. Of note, ESSKA has a long tradition of supporting basic science, highlighted in the prestigious Theo van Rens Award for the best scientific presentation, named after Professor Theo J. G. van Rens (1931–1986), one of the founding members of ESSKA [Journal of Experimental Orthopaedics intends to bridge the gap between orthopaedic basic science and clinics. Its goal is to publish papers related to the entire field of experimental orthopaedics, including physiological, pathological, and therapeutic aspects of cartilage, bone, tendons, ligaments, and other musculoskeletal tissues. Scientific excellence is the main criterion for publication. Another basic principle is to provide a peer review process that is both decisive and fair to authors, with a focus of a fast turnaround time. As we believe that the results of scientific research should be freely available to everyone to read and use, we have chosen an open access model, which is, among others, supported by such highly prestigious organizations such as the European Commission, the Howard Hughes Medical Institute, the Max Planck Society, the National Institutes of Health and the Wellcome Trust. The international Journal of Experimental Orthopaedics will thus enable clinicians and scientists to better work together in order to take a leading role in the publication of research in a way that is without restricted access to these results.The founders of the of ESSKA . The JouJournal of Experimental Orthopaedics, our goal is to put high quality basic science first, as the editorial decision making process is not driven by profits or scientific fashions but by pure academic excellence. We envision papers that are exciting, clearly written, and based on original data with a clinical background. In addition to research articles, the journal provides a forum to publish both comprehensive and focused reviews.At the Journal of Experimental Orthopaedics is thought to complement the esteemed Knee Surgery, Sports Traumatology, Arthroscopy journal, which focuses on clinical investigations. When Knee Surgery, Sports Traumatology, Arthroscopy was launched in 1993, Ejnar Eriksson, its founding editor, asked the question “Why another new scientific journal when there are already so many” [Journal of Experimental Orthopaedics with its excellent Editorial Board, together with its distinguished Board of Trustees, and its committed editorial team, will similarly flourish in the wake of such visionaries like Eriksson, van Rens, and many others, and invite you to select the Journal of Experimental Orthopaedics as your first choice to publish your best orthopaedic basic research.The so many” ? Now, 21


International Journal of Molecular Science has previously granted [The granted ,2,3, andInternational Journal of Molecular Science Best Paper Award” for 2015. Nominations were made by the Editorial Board Members chosen from all papers published in 2011. The awards are issued to reviews and research articles separately. We proudly reveal the following eight papers that have been chosen:We are therefore pleased to announce the “Research Article Award:First PrizeToni Safner, Mark P. Miller, Brad H. McRae, Marie-Josée Fortin and Stéphanie ManelComparison of Bayesian Clustering and Edge Detection Methods for Inferring Boundaries in Landscape GeneticsInt. J. Mol. Sci.2011, 12(2), 865–889; doi:10.3390/ijms12020865http://www.mdpi.com/1422-0067/12/2/865“This study evaluates different techniques available for identifying clusters and boundary detection within populations. It nicely demonstrates the potential of Bayesian spatial clustering algorithms.”—Dr. Guido R. M. M. Haenen“While somewhat specialized, this study can have valuable practical utility in understanding where geographic edges lie between subspecies.”—Prof. Dr. Stephen C. Bondy“The sheer breadth of the data, significance of conclusions and usefulness of results to other researchers.”—Prof. Dr. Nicholas DelihasAvailable online: Second PrizeThomas Schlorf, Manuela Meincke, Elke Kossel, Claus-Christian Glüer, Olav Jansen and Rolf MentleinBiological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance ImagingInt. J. Mol. Sci.2011, 12(1), 12–23; doi:10.3390/ijms12010012http://www.mdpi.com/1422-0067/12/1/12“The article investigated the uptake of different Iron oxide nanoparticles , retention and location in the cell, and their ability to be detected by MRI. This paper was well written and will be of use to people working in the area of metal oxide nanoparticle research.”—Dr. Terrence Piva“Usefulness of results to MRI research and possibly clinical uses.”—Prof. Dr. Nicholas DelihasAvailable online: Juan C. Garro Martinez, Pablo R. Duchowicz, Mario R. Estrada, Graciela N. Zamarbide and Eduardo A. CastroQSAR Study and Molecular Design of Open-Chain Enaminones as Anticonvulsant AgentsInt. J. Mol. Sci.2011, 12(12), 9354–9368; doi:10.3390/ijms12129354http://www.mdpi.com/1422-0067/12/12/9354“This paper presents an interesting development of models for prediction of antiepileptic activity of some enaminones.”—Prof. Dr. Fabio Marinelli“The paper inscribes in the nowadays open issue of modeling ringed vs. open-chain molecular behavior, intuitively yet also computationally emphasizing on the last instance, in binding with receptor sites towards reliable mechanistic QSARs.”—Dr. Mihai V. Putz“Of use to researchers and good data, i.e., ED50 exp. vs. ED50 pred Figures. 3,4”—Prof. Dr. Nicholas DelihasAvailable online: Third PrizeHaider Raza, Subbuswamy K. Prabu, Annie John and Narayan G. AvadhaniImpaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic RatsInt. J. Mol. Sci.2011, 12(5), 3133–3147; doi:10.3390/ijms12053133http://www.mdpi.com/1422-0067/12/5/3133“May contribute to better understand the etiology of diabetes and may lead to development of new therapeutic methods.”—Prof. Dr. Nicholas DelihasAvailable online: Antonio Iannitelli, Rossella Grande, Antonio Di Stefano, Mara Di Giulio, Piera Sozio, Lucinda Janete Bessa, Sara Laserra, Cecilia Paolini, Feliciano Protasi and Luigina Cellinidl-lactide-co-glycolide) (PLGA) Nanoparticles against Microbial BiofilmPotential Antibacterial Activity of Carvacrol-Loaded Poly, 5039–5051; doi:10.3390/ijms12085039http://www.mdpi.com/1422-0067/12/8/5039“This paper presents an innovative nanoparticle-based approach to disrupting biofilms, a major challenge in biomedicine.”—Prof. Dr.Vince RotelloAvailable online: Review Award:Alba Fernández-Sánchez, Eduardo Madrigal-Santillán, Mirandeli Bautista, Jaime Esquivel-Soto, Ángel Morales-González, Cesar Esquivel-Chirino, Irene Durante-Montiel, Graciela Sánchez-Rivera, Carmen Valadez-Vega and José A. Morales-GonzálezInflammation, Oxidative Stress, and ObesityInt. J. Mol. Sci.2011, 12(5), 3117–3132; doi:10.3390/ijms12053117http://www.mdpi.com/1422-0067/12/5/3117“A very comprehensive review on obesity, an inflammatory condition which represents a major risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer.”—Prof. Dr. Marcello Iriti“This is a very important topic, the authors did a nice job in reviewing it in an interesting way”—Dr. William Chi-shing Cho“This is a comprehensive review of the literature on obesity especially in regards the effects adipokines play in regards modulating oxidative stress and immunity in the host. This review article is one that will be used as a reference source for those working in obesity research.”—Dr. Terrence Piva“This Review presents a very well-considered discussion of the complex interrelationship of obesity and inflammation. An excellent starting point for anyone interested in the underlying causes of obesity-related inflammation.”—Prof. Dr. Vince Rotello“This Review provides a very clear and thorough overview of an area of research that is increasingly important. The authors convey the multifactorial nature of the factors that influence obesity and the review helps explain how our lifestyle is intimately linked with the obesity problem in industrialised countries and why weight loss is so difficult.”—Prof. Dr. Stephen A. Bustin“Good descriptions of factors related to obesity in Abstract, Fig. 1 and Conclusions and weight loss with nutritional and drug treatments.”—Prof. Dr. Nicholas DelihasAvailable online: Maryam Moravej and Diego MantovaniBiodegradable Metals for Cardiovascular Stent Application: Interests and New OpportunitiesInt. J. Mol. Sci.2011, 12(7), 4250–4270; doi:10.3390/ijms12074250http://www.mdpi.com/1422-0067/12/7/4250 “This review that describes the recent advances in biodegradable metallic stents, is of high quality and high impact.”—Prof. Dr. Fabio Marinelli“This review gives a relatively complete overview of the recent developments in metallic materials for biodegradable stents.”—Dr. Guido R. M. M. Haenen“This study on biodegradable stents is well-written annd has the potential for wide applicability. It is of broad relevance and may lead to very useful advances in medical science.”—Prof. Dr. Stephen C. Bondy“Fascinating discussion of biodegradable cardiovascular stents. But I am surprised at the lack of toxicity  and the degradation rate needs to be worked out.”—Prof. Dr. Nicholas DelihasAvailable online: Giuseppe Vasapollo, Roberta Del Sole, Lucia Mergola, Maria Rosaria Lazzoi, Anna Scardino, Sonia Scorrano and Giuseppe MeleMolecularly Imprinted Polymers: Present and Future ProspectiveInt. J. Mol. Sci.2011, 12(9), 5908–5945; doi:10.3390/ijms12095908http://www.mdpi.com/1422-0067/12/9/5908“This review is very interesting, because the topic covered is of great importance. It is written in a clear manner, and the citation of references is exhaustive.”—Prof. Dr. Fabio Marinelli“This is a forward-looking review in an area likely to develop a lot in the next few years.”—Prof. Dr. Stephen C. Bondy“Molecular imprinting technology seems throughly described and presented.”—Prof. Dr. Nicholas DelihasAvailable online: International Journal of Molecular Science and the scientific research field. On behalf of the Prize Awarding Committee and the Editorial Board of International Journal of Molecular Science, we would like to congratulate these teams for their excellent work. In recognition of their accomplishment, Dr. Stéphanie Manel, Dr. Rolf Mentlein, Dr. Juan C. Garro Martinez, Dr. Haider Raza and Dr. Antonio Di Stefano will receive a prize of 1000 CHF, 600 CHF, 600 CHF, 400 CHF and 400 CHF, respectively, and the privilege of publishing an additional paper free of charge in open access format in the International Journal of Molecular Science, after the usual peer-review procedure. Dr. José A. Morales-González, Dr. Diego Mantovani and Dr. Giuseppe Vasapollo will receive the privilege of publishing an additional research article free of charge in open access format in the International Journal of Molecular Science, after the usual peer-review procedure.We believe that these eight exceptional papers are valuable contributions to the Prize Awarding CommitteeProf. Dr. Anthony LemariéProf. Dr. Nicholas DelihasProf. Dr. Fabio MarinelliProf. Dr. Pamela LeinDr. Guido R. M. M. HaenenProf. Dr. Paul EvansProf. Dr. Helmut SegnerProf. Dr. Stephen C. BondyProf. Dr. Ian A. NichollsDr. Terrence PivaProf. Dr. Kaixun HuangProf. Dr. Vince RotelloProf. Dr. Kurt A. JellingerProf. Dr. Vladimír KřenDr. Lam-Son Phan TranDr. Walter HerzogProf. Dr. Marcello IritiDr. William Chi-shing ChoDr. Marie-Christine BacchusDr. Xiaofeng JiaDr. Mateus Webba da SilvaProf. Dr. Zdenek WimmerDr. Mihai V. Putz


Aortoenteric fistula is an uncommon but life-threatening cause of gastrointestinal blood loss. We report a case of a 70-year-old man who presented to the emergency department with an episode of melena and infection in the left inguinal region. Diagnosis of secondary aortoenteric fistula was made between the left limb of the aortobifemoral graft and the descending colon. We performed excision of the infected graft and in situ silver acetate coating of prosthetic vascular graft replacement  on the patient. This study reports a rare type of secondary aortoenteric fistula to the left colon, and it describes an unusual and successful surgical treatment. Antimicrobial coating of prosthetic vascular grafts may be a good alternative in the presence of graft infection associated with aortoenteric fistula because in situ grafts may carry an increased risk of reinfection. Aortoenteric fistula (AEF) is a rare and life-threatening condition associated with diagnostic challenges. AEFs are classified as primary or secondary depending on their etiology. Primary aortoenteric fistula occurs when an erosive aortic segment opens into the adjacent gastrointestinal lumen. This commonly occurs in abdominal aortic aneurysms. On the other hand, secondary aortoenteric fistula is a complication of aortic reconstructive surgery involving the use of vascular grafts, and it is located between the graft and the adjacent segment of the intestines –3.Secondary AEF has a higher incidence rate than primary AEF, with a reported incidence between 0.36 and 1.6% . On averIn this case report, a very rare form of secondary AEF, an aortocolonic fistula formation, is presented along with a discussion regarding the surgical technique applied. Staphylococcus aureus in the wound samples, antibiotic treatment according to the antibiogram results was started. Abdominal ultrasound showed a soft tissue image consistent with infection in the perivascular soft tissue around the left limb of the aortobifemoral bypass graft. Contrast enhanced abdominal computerized tomography (CT) suggested the presence of a suspicious adherence between the left limb of the graft and rectosigmoidal junction. Contrast enhanced CT angiography and digital subtraction angiography (DSA) did not reveal any pathologies suggesting AEF. The patient had diarrhea during his clinical follow-up, and, due to the presence of fresh blood in stool microscopy, a colonoscopy was scheduled by the department of gastroenterology. Colonoscopy showed a blood covered mass lesion with irregular borders located at centrally ulcerative mucosal areas and its appearance was consistent with the graft . Since the patient had a prior history of aortic grafting surgery, the findings suggested an AEF and graft infection, which prompted urgent surgical treatment. During the surgery, the left limb of the aortobifemoral graft was observed to be infected and passing transversely into the colon at its distal end. The part of the graft adhering to the colon was separated together with the resection of the same colonic segment, and a colostomy was performed. The left limb of the graft was resected from the bifurcation and from its distal adherence point to the CFA. InterGard Silver polyester graft  interposed retroperitoneally into a new tunnel. The proximal part of the silver-coated graft was anastomosed to the resected left limb of the aortobifemoral graft proximally and to the CFA distally. The histopathological examination of the resected colonic segment showed a chronic inflammatory process due to foreign body reaction. Following the operation, the patient completed his course of antibiotics and was subsequently discharged. No postoperative neuromuscular deficits or infections developed postoperatively. Two-year follow-up revealed a complete healing of the inguinal wound and no complaints of claudication.Written informed consent was taken from the patient for publication of this case report. A 70-year-old male patient was admitted to our clinic with abdominal pain and a left inguinal wound with discharge. Approximately 9 months ago, the patient had undergone an aortobifemoral bypass procedure with dacron graft in an another center, after a diagnosis of chronic peripheral arterial disease. In the following course of events, two separate occasions of debridement were performed for the left inguinal lesion with discharge. No history of massive bleeding with hematemesis or hematochezia was present, and the patient was hemodynamically stable at the time of admission. Hematological test results were as follows: Hb = 12.7 g/dL; Htc = 39.3%; WBC = 18.2. Due to the growth ofSecondary aortoenteric fistulae occur as a result of iatrogenic causes, mostly as a complication of aortic interventions. Despite the exact information on its incidence due to a lack of epidemiological data, the estimated incidence is around 1% . Most ofThe pathogenesis of secondary aortoenteric fistulae is controversial with a number of different mechanisms proposed for its occurrence. One of the most significant factors for the development of this condition is the presence of graft infection and inflammation, while another important factor is the presence of a continuous pulsatile movement between the graft and intestines  , 7. PseuClinical presentation involves infectious and hemorrhagic components. Most of the symptoms are nonspecific, such as abdominal pain, high fever, bleeding, and shock , 7, 8. TImmediately after a diagnosis of secondary aortoenteric fistula is made, the patient has to be operated on as soon as possible, since mortality rate is 100% without treatment . SeveralIn patients with aortoenteric fistula secondary to previous abdominal aortic surgery, particularly in those with weak collateral circulation of the lower extremity, silver-coated in situ graft replacement may help minimize the early postoperative risk of infections and amputations.Colonoscopy revealed ulcerative mucosal areas and aortic graft covered by thrombus.