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Objective The aim of this study was to report the technical aspects and outcomes of late open conversion (LOC) after endovascular aneurysm repair (EVAR) in a single center by using exclusively infrarenal clamping of the endograft as an alternative to suprarenal or supraceliac aortic clamping. Methods A retrospective analysis of EVAR requiring late explantation (>30 days) from January 1996 to October 2016 was performed. Patients' demographics, type of endograft, duration of implantation, reason for removal, extent of stent graft removal, type of reconstruction, 30-day mortality, postoperative complications, and long-term survival were obtained for analysis. Results During the study period, 28 patients required LOC. The mean age at conversion was 75.11 ± 6.65 years; 26 of 28 (92.86%) were male. Grafts were excised after a median of 41.4 months (range, 5.97-112.67 months), with 21 of 28 explantations (75%) performed electively. Multiple types of EVAR devices have been explanted; suprarenal fixation was present in 75% of the cases. The indication for LOC was the presence of an endoleak in 27 cases (20 type I, 4 type II associated with aneurysm growth, 3 type III, and 3 endotensions; in 3 cases, multiple types of endoleak were present) and graft thrombosis in 1 case. All patients underwent a transperitoneal approach with infrarenal clamping. No patient required revascularization of visceral or renal vessels. Complete removal of the stent graft was performed in 8 of 28 cases, partial removal in the remaining 20 cases (with conservation of the proximal portion in 16 of 20 cases). Technical success was 100%. Overall 30-day mortality was 7.14% (2/28). The 30-day mortality was 9.5% in elective patients and 0% in the urgent setting; this difference was not statistically significant ( P = .56). Postoperative kidney injury rate was 7.7% (2/26). Mean follow-up was 47.37 ± 55.67 months (range, 0.23-175.07 months). The estimated 5-year survival rate was 78%. No aneurysm-related death or additional procedure occurred during follow-up. Conclusions LOC after EVAR using infrarenal clamping of the endograft is a feasible and effective technique, with satisfactory postoperative mortality and morbidity. This method allows simplification of the surgical technique and may avoid renal and visceral complications related to suprarenal or supraceliac clamping.

Intrarenal interleukin-15 (IL-15) participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15) isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC) to peritumoral (ptumTEC), tumoral (RCC), and cancer stem cells (CSC/CD105 + ). RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα) chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15) isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα). This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105 + , where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105 + from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa) displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, "apparently normal" ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral "preneoplastic" environment committed to favor tumor progression.

Background Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFVs) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries. Methods We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery. Results The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate. Conclusion The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFVs. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU.

Purpose To evaluate the performance of the first years since the beginning of a mammographic population-based screening program. Materials and methods Women aged 49–69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared. Results A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p = 0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25%, 7/28) was higher than that for true ICs (10%, 7/71), although all these differences were not significant (p ≥ 0.480). Conclusion These results showed the possibility to comply with European Community standards in the first years of a screening program implementation.

Experiments in IL-15(-/-) and IL-15Rα(-/-) mice show that intra-renal IL-15, through IL-15Rα behaves as an epithelial survival factor. Recent data highlight new functions of IL-15 in renal homeostasis mediated by IL-15Rγ (CD132). Indeed, in CD132+ renal epithelial tubular cells IL-15 preserves E-cadherin expression inhibiting epithelial-mesenchymal transition (EMT). By contrast, during allograft rejection, the increased intra-graft IL-15 expression favors tubular destruction facilitating the intraepithelial recruitment of CD8 T cells expressing the E-cadherin ligand CD103. In renal cancer, loss of CD132 by epithelial cells defines a tumoral microenvironment where IL-15 triggers E-cadherin down-regulation and EMT. Finally, in CD132+ renal cancer stem cells IL-15 induces the generation of non-tumorigenic epithelial cells sensitive to cytotoxic drugs. These findings are discussed in the light of IL-15-based immunotherapy for renal cancer.

This paper describes an applicative software tool, named IONORT (IONOspheric Ray Tracing), for calculating a three-dimensional ray tracing of high frequency waves in the ionospheric medium. This tool runs under Windows operating systems and its friendly graphical user interface facilitates both the numerical data input/output and the two/three-dimensional visualization of the ray path. In order to calculate the coordinates of the ray and the three components of the wave vector along the path as dependent variables, the core of the program solves a system of six first order differential equations, the group path being the independent variable of integration. IONORT uses a three-dimensional electron density specification of the ionosphere, as well as by geomagnetic field and neutral particles-electrons collision frequency models having validity in the area of interest., 25 pages, 7 figures, 2 tables

Primary human epithelial renal cells of normal (HRE), paratumoral (pTEC) and tumoral (RCC) origin display important differences, concerning the expression and biological effects of the IL-15/IL-15R system that deeply influences the evolution of the tumour microenvironment. A major distinguishing feature is represented in RCC and pTEC by the loss of the γc chain leading to the assembly of a IL-15Rαβ heterodimer that in response to physiologic concentrations of IL-15 initiates the process of their epithelial–mesenchymal transition (EMT). In contrast, this treatment in HRE cells, which display the IL-15Rαβγc heterotrimer, causes opposite effects inhibiting their drift towards EMT. Thus, IL-15 at physiologic concentrations displays novel functions acting as a major regulator of renal epithelial homeostasis. As second distinguishing feature, RCC and pTEC but not HRE cells express a trans-membrane-bound IL-15 (tmb-IL-15) able to deliver a reverse signal in response to the soluble IL-15Rα chain inducing their EMT. In conclusion, comparison of primary normal (HRE) to primary pathological cells (pTEC and RCC) highlights two major issues: (1) IL-15 is a major regulator of epithelial homeostasis; (2) “apparently normal” pTEC cells, could contribute to organize a generalized “pre-neoplastic” environment committed to favour tumour progression.

Cultured blood CD34(+) progenitors from patients with myeloid metaplasia with myelofibrosis (MMM) failed to differentiate into natural killer (NK) cells with recombinant interleukin (IL)-15. No NK cells either could be induced in coculture with IL-15-expressing fibroblasts from MMM patients' spleens. The impaired NK differentiation could be circumvented by using normal blood CD34(+) cells in the coculture. In this case, cell-to-cell contact and IL-15 interaction were crucial for NK cell differentiation. Pretreatment of normal CD34(+) progenitors with anti-IL-15 monoclonal antibody markedly reduced NK cell production while MMM fibroblast pretreatment did not. Both normal and MMM progenitors constitutively expressed IL-15. Analysis of endogenous IL-15 signaling pathway revealed a constitutive gammac/Jak3 association and STAT3 activation in the two types of progenitors. Anti-IL-15 monoclonal antibody treatment caused a downregulation of IL-15 signaling in normal but not MMM blood cells. The impaired NK differentiation in MMM may thus arise from a deregulated control of an endogenous IL-15 involved in hematopoietic progenitors' lymphoid differentiation.

Background . We have shown that the administration of exogenous Augmenter of Liver Regeneration protein in intact rats i) regulates mitochondrial gene expression by inducing the transcription and translation of the nuclear-encoded mitochondrial transcription factor A, and ii) inhibits the lytic activity of liver-resident Natural Killer cells. Aims. The present investigation was carried out to study the effect, in intact rats, of exogenous administration of Augmenter of Liver Regeneration protein on Interferon-γ, a cytokine produced by activated Natural Killer cells and known to control the expression of mitochondrial transcription factor A, a nuclear gene responsible for mitochondrial metabolism. Methods. Interferon-γ was measured as messenger RNA in liver-derived mononuclear leukocytes and as protein in liver-derived Natural Killer cells after a single injection of Augmenter of Liver Regeneration protein. Results. The data obtained demonstrate that: i) in intact rats, Augmenter of Liver Regeneration protein administration induces a reduction of Interferon-γ in the liver-resident Natural Killer cells and ii) the administration of Interferon-γ in 70% hepatectomized rats is followed by a significant reduction both of the mitochondrial transcription factor A expression and of liver regeneration. Conclusions. These data demonstrate the pivotal role of Augmenter of Liver Regeneration as Growth Factor and as immunoregulator by controlling, through Interferon-γ levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident Natural Killer cells.

The in vitro sensitivity of Helicobacter pylori to rifaximin, a new rifamycin antibiotic, was evaluated in 40 clinical isolates by the agar dilution method. Rifaximin showed good activity, with a 50% minimum inhibitory concentration of 4 mg/L −1 . Consequently, we assessed rifaximin in H pylori —positive patients. Overall, 71 patients with upper gastrointestinal symptoms (35 men and 36 women; aged 19 to 73 years, mean, 45.6 years) were found to have H pylori —associated gastritis. The first 30 consecutive patients received monotherapy with rifaximin 600 mg three times a day (TID) for 14 days. The 41 patients enrolled thereafter were allocated in an open, randomized fashion to four different treatment groups for 14 days: (1) rifaximin 600 mg TID and colloidal bismuth subcitrate 240 mg twice a day (BID) (n = 10); (2) rifaximin 600 mg TID and omeprazole 20 mg BID (n = 10); (3) rifaximin 600 mg TID and amoxicillin 1 g BID (n = 10); or (4) rifaximin 1800 mg TID and metronidazole 500 mg TID (n = 11). Upper gastrointestinal symptoms (pyrosis, bloating, epigastric pain, and nausea) were recorded and assessed before and 4 weeks after treatment. Patients were assessed by endoscopy, histology, CP test, culture, and serology (immunoglobulin G [IgG] to H pylori ) at entry. Sixty-seven patients were available for follow-up 4 weeks after the completion of treatment. A statistically significant improvement in symptoms was seen in patients treated with rifaximin and rifaximin plus colloidal bismuth subcitrate. No statistically significant differences in degree of improvement in endoscopic and histologic findings were seen among the five treatment groups. A statistically significant decrease in the mean IgG value after treatment was found for rifaximin, rifaximin plus colloidal bismuth subcitrate, and rifaximin plus omeprazole. The overall eradication rate was 43%. These results suggest that rifaximin may be an effective antibiotic against H pylori infection and is worthy of further study.

Endovascular treatment of posttraumatic pseudoaneurysms has become a viable less-invasive option when compared with open repair. In this study, we present a case of a posttraumatic pseudoaneurysm of the posterior tibial artery in a 34-year-old man treated with endovascular stent grafting. An extensive review of the literature has been performed.

Interferon-alpha (IFN-alpha) is currently the only treatment for patients with chronic hepatitis C. Yet it can induce acute renal transplantation rejection possibly by stimulating humoral responses. We tested patient sera for detection of donor-specific anti-human leukocyte antigen (HLA) antibodies observing an increased panel-reactive antibodies value after IFN-alpha therapy. Then, we also investigated whether antiviral treatment with IFN-alpha was related to an increased and/or different production of class I and class II anti-HLA antibodies. Patient sera analysis performed by a cytofluorimetric method using flow PRA tests showed the appearance of new HLA-antibody specificities. This study underlined that INF-alpha therapy modifies a patient's immune profile; hence, it is recommended to confirm HLA-antibody specificities after treatment in order to protect recipients from enhanced rejection risk owing to a false-negative donor-specific cross-match.

Aneurysms of the gluteal artery, true or false, are rare diseases which mostly occur after pelvic fractures or penetrating traumas. We report on a case of a 77-year-old woman who developed a 16 cm large right gluteal aneurysm. Echo-color-doppler, CT scan and angiography confirmed the clinical suspicion. The patient was successfully treated with endoaneursymorrhaphy, upon temporary clamping of the hypogastric artery using an extraperitoneal approach. In case of very large gluteal aneurysm we believe that open surgical treatment is still to prefer the endovascular procedure.