Recanalization of the Native Artery in Patients with Bypass Failure

Our objective was to evaluate the possible role of endovascular recanalization of occluded native artery after a failed bypass graft in the case of either acute or chronic limb-threatening ischemia otherwise leading to amputation. In a single-center retrospective clinical analysis, from January 2004 to March 2007 we collected 31 consecutive high-surgical-risk patients (32 limbs) with critical limb ischemia following late ([30 days after surgery) failure of open surgery bypass graft reconstruction. All patients deemed unfit for surgery underwent tentative endovascular recanalization of the native occluded arterial tract. The mean follow-up period was 24 (range, 6–42) months. Technical success was achieved in 30 (93.7%) of 32 limbs. The cumulative primary assisted patency calculated by Kaplan–Meyer analysis was 92% and 88%, respectively, at 12 and 24 months. The limb salvage rate approached 90% at 30 months. In conclusion, our experience shows the feasibility of occluded native artery endovascular recanalization after a failed bypass graft, with optimal results in terms of midterm arterial patency and limb salvage. Our opinion is that successful recanalization of the arterial tract previously considered unsuitable for endovascular approach is allowed by improved competency and experience of vascular specialists, as well as the advances made in catheter and guidewire technology. This group of patients would previously have been relegated to repeat bypass grafts, with their inherently inferior patency and recognized added technical demands. We recognize previous surgical native artery disconnection and lack of pedal runoff to be the main cause of technical failure. Keywords Native artery Bypass failure Endovascular recanalizatio

Passive Margin evolution and control on natural gas leakage in the Orange Basin South Africa

Throughout exploration Block 2 of the Orange Basin offshore the South African continental margin, different natural gas leakage features and the relationship between natural gas leakage with structural and stratigraphic elements were studied. This study also quantifies liquid/gas hydrocarbon generation, migration and seepage dynamics through the post-rift history of the basin. The interpretation of seismic data reveals two mega-sequences: Cretaceous and Cenozoic that are subdivided by major stratigraphic unconformities into 5 and 2 sub-units, respectively. The basin is also divided into 2 structural domains: 1. an extensional domain characterized by basinward dipping listric normal faults rooted at the Cenomanian/Turonian level identified between 500 to 1500 m of present-day depth, 2. a compressional domain that accommodates the up-dip extension on the lower slope, and which is characterized by landward dipping thrust faults. One hundred and thirteen observed gas chimneys are identified and classified into .stratigraphically-controlled (sa-c) and structurally-controlled (s-c) chimneys. The ratio of s-c versus s-ac chimneys is estimated as 2:5, which suggest a strong stratigraphic control on natural gas leakage. The chimneys either terminate at the seafloor where active leaking gas is manifested by pockmarks, or are sealed within the Miocene (14 Ma) sequence as paleo-pockmarks. The s-c chimneys are located along the normal faults in the extensional domain, and terminate as seafloor mounds up to 1500 m in diameter and with heights between 10 to 50 m. The sa-c pockmarks range between 100 to 400 m in diameter, and are linked to stratigraphic onlaps and pinch-outs within the Aptian sequence. Several giant chimneys, with diameters of more than 7 km, are also identified. At least one of these displays apparent internal gravitational collap.se structures. Bright spots indicative of gas presence within these large chimneys were identified, but there is no evidence of acoustic turbidity or seismic pull-downs within these large structures. This suggests the giant chimneys are inactive paleo-gas-escape structures. Modelling suggests that gas from the lower Aptian and the Barremian source rocks migrates laterally-updip to the proximal parts of the basin where it accumulates beneath the Cenomanian/Turonian sequence that acts as a regional seal. Across the shelf-break and the upper slope, chimneys and pockmarks are fed from younger Cenomanian/Turonian source rocks. The migration model also indicates that fluids are about 24 times more likely to flow out of the study area than to be preserved within it. Since methane gas escaping across the sea floor into the exosphere (combined hydrosphere and atmosphere) may contribute to Earth s climate fluctuations, and because escaping gas must have been cut off when at least half of identified s-c chimneys were sealed within the Mioeene .sequenee, deerease of gas escape along the southern African continental margin may have to be factored into global Neogene cooling models

Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up.

Angiogenesis is a critical step in the growth, invasive progression and metastatic spread of solid tumors. We investigated the importance of tumor necrosis, and microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) immunohistochemical expression in a large series of clear cell renal carcinomas treated with radical nephrectomy and assessed the prognostic value of their expression in terms of patient survival at long-term follow up. Fifty patients with clear cell RCC were examined. The features considered when evaluating the patients were age, tumor size and grade, intratumoral vascular and renal capsula invasion, histological necrosis, and MVD, vascular and tumoral cell VEGF, and vascular, tumoral cytoplasmic and nuclear HIF-1α expression on the histologic specimens. All considered parameters were correlated with patient specific survival. Mean age was 62.06 ± 6.8 years. Median follow-up was 191.66 months; median survival was 120.86 months. Twenty-one patients developed metastases in the follow-up. Tumor necrosis, microvascular invasion and renal capsula infiltration are more likely to occur in high stage and grade RCC; cytoplasmic HIF-1α is highly expressed in high grade RCC. Survival is dependent upon tumor stage and grade, the presence of intratumoral vascular invasion and capsular infiltration, and tumor necrosis; MVD also resulted as being an important prognostic factor. VEGF and HIF-1α correlate with prognosis in high stage tumors where VEGF is the most important independent prognostic factor for cancer specific death. The histological and immunohistochemical parameters considered in our study can influence disease recurrence and survival in RCC

Enhancement of gene targeting in human cells by intranuclear permeation of the Saccharomyces cerevisiae Rad52 protein

The introduction of exogenous DNA in human somatic cells results in a frequency of random integration at least 100-fold higher than gene targeting (GT), posing a seemingly insurmountable limitation for gene therapy applications. We previously reported that, in human cells, the stable over-expression of the Saccharomyces cerevisiae Rad52 gene (yRAD52), which plays the major role in yeast homologous recombination (HR), caused an up to 37-fold increase in the frequency of GT, indicating that yRAD52 interacts with the double-strand break repair pathway(s) of human cells favoring homologous integration. In the present study, we tested the effect of the yRad52 protein by delivering it directly to the human cells. To this purpose, we fused the yRAD52 cDNA to the arginine-rich domain of the TAT protein of HIV (tat11) that is known to permeate the cell membranes. We observed that a recombinant yRad52tat11 fusion protein produced in Escherichia coli, which maintains its ability to bind single-stranded DNA (ssDNA), enters the cells and the nuclei, where it is able to increase both intrachromosomal recombination and GT up to 63- and 50-fold, respectively. Moreover, the non-homologous plasmid DNA integration decreased by 4-fold. yRAD52tat11 proteins carrying point mutations in the ssDNA binding domain caused a lower or nil increase in recombination proficiency. Thus, the yRad52tat11 could be instrumental to increase GT in human cells and a ‘protein delivery approach’ offers a new tool for developing novel strategies for genome modification and gene therapy applications

Carotid artery stenting: a single-centre experience with up to 8 years' follow-up

Carotid artery stenting (CAS) may be an alternative to surgical endoarterectomy not only in high-risk patients. We report results in the endovascular treatment of carotid artery disease with up to 8 years' follow-up. In this retrospective study, we analysed data from 853 consecutive patients (946 arteries) treated for carotid artery stenosis between April 1999 and March 2007; 491 (52%) arteries were symptomatic and 455(48%) were asymptomatic. Preprocedural evaluation of the patients was performed with echo Doppler, magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) and a neurological examination. A cerebral protection device was used in 879 (92.9%) procedures. Anti-platelet therapy was administered before and after the procedure. All patients were included in a follow-up of up to 8 years. Technical success was achieved in 943 (99.6%) lesions. At 30 days, there was a 0.21% (n = 2) death rate, a 0.42% major stroke rate, a 1.69% minor stroke/transient ischaemic attack (TIA) rate and a combined 2.32% TIA/stroke and death rate. During follow-up, echo Doppler evidenced restenosis in 39 (4.85%) cases; of these, only five, presenting restenosis > 80%, were treated with an endovascular reintervention. At the long-term follow-up, two strokes (0.23%) were reported, which both occurred within the first 2 years. In our experience, carotid artery stenting seems to be a safe and effective treatment, providing satisfactory long-term clinical results

A proteomics approach to the study of bleomycin- induced lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most severe lung fibrotic form and very few pharmacological therapies are available at present. Key events in the onset of the disease are the activation of fibroblasts to myofibroblasts and the production and release of extracellular matrix (ECM) and molecular factors. Primary murine lung fibroblasts were isolated and their activation induced by Bleomycin (BLM) treatment. Extracellular Vesicles (EV) were isolated and protein extracted. Released soluble proteins (Secretome) and EV-derived proteins were reduced, alkylated and trypsin digested. A nano-LC-MS/MS SWATHTM approach was used for the proteomics analyses. Specific proteins with a putative role in the transition from physiological to fibrotic conditions, such as several matrix metalloproteinases (MMPs), osteopontin (OPN), chitinase-3-like protein1 (CHI3L1) and CD44 resulted differentially released from BLM-treated fibroblasts as compared with untreated lung fibroblasts. Our results provide further understanding of the pathophysiological features of lung fibrosis, and suggest specific target for pharmacological treatments

Hospital Organization and Importance of an Interventional Radiology Inpatient Admitting Service:Italian Single-Center 3-year Experience

In June 2005 a Complex Operating Unit of Interventional Radiology (COUIR), consisting of an outpatient visit service, an inpatient admitting service with four beds, and a day-hospital service with four beds was installed at our department. Between June 2005 and May 2008, 1772 and 861 well-screened elective patients were admitted to the inpatient ward of the COUIR and to the Internal Medicine Unit (IMU) or Surgery Unit (SU) of our hospital, respectively, and treated with IR procedures. For elective patients admitted to the COUIR’s inpatient ward, hospital stays were significantly shorter and differences between reimbursements and costs were significantly higher for almost all IR procedures compared to those for patients admitted to the IMU and SU (Student’s t-test for unpaired data, p\0.05). The results of the 3-year activity show that the activation of a COUIR with an inpatient admitting service, and the better organization of the patient pathway that came with it, evidenced more efficient use of resources, with the possibility for the hospital to save money and obtain positive margins (differences between reimbursements and costs). During 3 years of activity, the inpatient admitting service of our COUIR yielded a positive difference between reimbursements and effective costs of €1,009,095.35. The creation of an inpatient IR service and the admission of well-screened elective patients allowed short hospitalization times, reduction of waiting lists, and a positive economic outcome. Keywords Inpatients Hospitalization Costs Reimbursement

Tau-dependent HDAC1 nuclear reduction is associated with altered VGluT1 expression

During AD pathology, Tau protein levels progressively increase from early pathological stages. Tau altered expression causes an unbalance of Tau subcellular localization in the cytosol and in the nuclear compartment leading to synaptic dysfunction, neuronal cell death and neurodegeneration as a consequence. Due to the relevant role of epigenetic remodellers in synaptic activity in physiology and in neurodegeneration, in particular of TRIM28 and HDAC1, we investigated the relationship between Tau and these epigenetic factors. By molecular, imaging and biochemical approaches, here we demonstrate that Tau altered expression in the neuronal cell line SH-SY5y does not alter TRIM28 and HDAC1 expression but it induces a subcellular reduction of HDAC1 in the nuclear compartment. Remarkably, HDAC1 reduced activity modulates the expression of synaptic genes in a way comparable to that observed by Tau increased levels. These results support a competitive relationship between Tau levels and HDAC1 subcellular localization and nuclear activity, indicating a possible mechanism mediating the alternative role of Tau in the pathological alteration of synaptic genes expression

INVESTIGATING THE SEISMIC RESPONSE OF URM WALLS WITH IRREGULAR OPENING LAYOUT THROUGH DIFFERENT MODELING APPROACHES

The façade and internal walls of unreinforced masonry (URM) buildings often present an irregular opening layout, due to architectural reasons or modifications to the structure, which make the expected seismic damage pattern less predictable a priori. Therefore, the discretization of the walls in structural components is not standardized, conversely to cases with a regular opening layout for which the available modeling methods are corroborated by seismic damage surveys reporting recurrent failure patterns. The structural component discretization is a relevant step for the code-conforming seismic assessment, typically based on comparing the internal forces and drifts of each component to strength criteria and drift thresholds. Therefore, the lack of well-established approaches can significantly influence the assessment. The issue is even more evident when the structural components must be identified a priori in the modeling stage, namely for equivalent frame models. The applicability of available methods for discretization of URM walls with irregular opening layout has been already investigated in literature, but a conclusive judgment requires further studies. In this context, this paper presents an overview of the preliminary results addressing the numerical modeling of this type of walls within the framework of the DPC-ReLUIS 2022-2024 project (Subtask 10.3), funded by the Italian Department of Civil Protection. The Subtask aims to propose consensus-based recommendations for researchers and practitioners which can contribute to harmonize the use of different modeling approaches. Seven research groups are involved in the research, adopting different modeling approaches and computer codes, but similar assumptions and the same analysis method (pushover) are used. The benchmark URM structure illustrated in the paper is a two-story wall from which four configurations with increasing irregularity of opening layout were derived. The results of four modeling approached are presented. Three of them reproduce the mechanical response of masonry at the material scale by means of FE models implemented in OpenSees, DIANA and Abaqus software, while the remaining approach describes the mechanical response of masonry at the macro-element scale in 3DMacro software. Results were compared in terms of capacity curves, predicted failure mechanisms and evolution of internal forces in piers. The adoption of consistent assumptions among the different approaches led to an overall agreement of predictions at both wall and pier scales, particularly in terms of damage pattern with higher concentration of damage at the ground story. Despite that, differences on the pushover curves have been highlighted. They are mainly due to some deviations of the internal forces in squat piers deriving from a complex load flow in these elements