Endovascular therapies for hepatic artery stenosis post liver transplantation.

PURPOSE: To evaluate primary patency at 12 months after endovascular therapies in hepatic artery stenosis. METHODS: A retrospective review of all endovascular interventions for hepatic artery stenosis (HAS) after liver transplantation that occurred between June 2013 and November 2020 was performed at a single institution in France. Follow up occurred from 1 month to 4 years (median 15 months). The treatment consisted of dilation with a balloon or stent. We analyzed short-term (technical success and complications) and long-term outcomes (liver function, arterial patency, graft survival at 12 months (GS), and reintervention). We also compared percutaneous balloon angioplasty (PBA) with stent placement. PBA alone was used if < 30% residual stenosis of the hepatic artery was achieved. Stenting was performed if there was greater than 30% residual stenosis and in the case of complications (dissection or rupture). RESULTS: A total of 18 stenoses were suspected on the basis of routine surveillance duplex ultrasound imaging (peak systolic velocity > 200 cm/s, systolic accelerating time > 10 ms and resistive index < 0.5), all of which were confirmed by angio CT, but only 17 were confirmed by angiography. Seventeen patients were included (14 males, mean age 57 years; and three females, mean age 58 years). Interventions were performed in 17 cases (95%) with PBA only (5/17), stent only (5/17) or both (4/17). Immediate technical success was 100%. Major complications occurred in 1 of 17 cases (5.8%), consisting of target vessel dissection. The analysis of the three (groups PBA only, stent only or both) showed the same procedural success (100%), GS (100%) and normal liver function after the procedures but different rates of complications (20% vs. 0% vs. 0%), arterial patency at 12 months (60% vs. 80% vs. 85%) (p = 0.4), early stenosis (40% vs. 80% vs. 0%) or late stenosis (60% vs. 20% vs. 100%) and requirement for reintervention (40% vs. 20% vs. 14%) (p = 0.56). CONCLUSION: This study suggests that PBA, stent, or both procedures show the same primary patency at 12 months. It is probably not a definitive answer, but these treatments are safe and effective for extending graft survival in the context of graft shortages.

Quantification of diffuse myocardial fibrosis using CMR extracellular volume fraction and serum biomarkers of collagen turnover with histologic quantification as standard of reference.

PURPOSE: To compare the assessment of diffuse interstitial myocardial fibrosis in valvular diseases using cardiac magnetic resonance (CMR) extracellular volume fraction (ECV) quantification and serum biomarkers of collagen turnover using results of myocardial biopsy as standard of reference. MATERIALS AND METHODS: This prospective monocentric study included consecutive patients before aortic valvular replacement. All patients underwent: i), 1.5T CMR with pre and post contrast T1 mapping sequence and ECV computation; ii), serum quantification of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) and iii), myocardial biopsies were collected during surgery to assess collagen volume fraction (CVF). Patients with coronary artery disease were excluded. Correlation between native T1, ECV, CVF and serum biomarkers were assessed using Pearson correlation test. Agreement between basal anteroseptal ECV with global ECV was assessed using Bland-Altman test. RESULTS: Twenty-one patients, 16 with aortic stenosis and 5 with aortic regurgitation were included. There were 12 men and 9 women with a mean age of 74.1±6.8 (SD) years (range: 32-84 years). Mean global ECV value was 26.7±2.7 (SD) % (range: 23.4-32.5%) and mean CVF value was 12.4±9.7% (range: 3.2-25.7%). ECV assessed at the basal anteroseptal segment correlated moderately with CVF (r=0.6; P=0.0026). There was a strong correlation and agreement between basal anteroseptal ECV and global ECV, (r=0.8; P<0.0001; bias 5.4±6.1%) but no correlation between global ECV and CVF (r=0.5; P=0.10). Global ECV poorly correlated with serum TIMP-1 (r=0.4; P=0.037) and MMP-2 (r=0.4; P=0.047). No correlation was found between serum biomarkers and basal anteroseptal- ECV or native T1. CONCLUSION: In patients with severe aortic valvulopathy, diffuse myocardial fibrosis assessed by anterosepto-basal ECV correlates with histological myocardial fibrosis. Anteroseptobasal ECV strongly correlates with global ECV, which poorly correlates with TIMP-1 and MMP-2, serum biomarkers involved in the progression of heart failure.

Fusion Imaging to Guide Thoracic Endovascular Aortic Repair (TEVAR): A Randomized Comparison of Two Methods, 2D/3D Versus 3D/3D Image Fusion.

PURPOSE: To compare the accuracy of two-dimensional (2D) versus three-dimensional (3D) image fusion for thoracic endovascular aortic repair (TEVAR) image guidance. MATERIALS AND METHODS: Between December 2016 and March 2018, all eligible patients who underwent TEVAR were prospectively included in a single-center study. Image fusion methods (2D/3D or 3D/3D) were randomly assigned to guide each TEVAR and compared in terms of accuracy, dose area product (DAP), volume of contrast medium injected, fluoroscopy time and procedure time. RESULTS: Thirty-two patients were prospectively included; 18 underwent 2D/3D and 14 underwent 3D/3D TEVAR. The 3D/3D method allowed more accurate positioning of the aortic mask on top of the fluoroscopic images (proximal landing zone error vector: 1.7 ± 3.3 mm) than was achieved by the 2D/3D method (6.1 ± 6.1 mm; p = 0.03). The 3D/3D image fusion method was associated with significantly lower DAP than the 2D/3D method (50.5 ± 30.1 Gy cm2 for 3D/3D vs. 99.5 ± 79.1 Gy cm2 for 2D/3D; p = 0.03). The volume of contrast medium injected was significantly lower for the 3D/3D method than for the 2D/3D method (50.6 ± 22.9 ml vs. 98.4 ± 47.9 ml; p = 0.002). CONCLUSION: Higher image fusion accuracy and lower contrast volume and irradiation dose were observed for 3D/3D image fusion than for 2D/3D during TEVAR. LEVEL OF EVIDENCE: II, Randomized trial.

Onyx Migration Into the Anterior Spinal Artery During Lumbar Artery Embolisation: an Adverse Event.

INTRODUCTION: The impact of sequential lumbar and intercostal artery occlusion on the risk of spinal cord ischaemia was evaluated; however, an adverse event (paraplegia) was encountered, which resulted in study interruption. Investigations were carried out to understand the reasons for the paraplegia. REPORT: To develop a porcine model of spinal cord ischaemic preconditioning prior to extensive thoraco-abdominal aneurysm endovascular aortic repair, the lumbar arteries were selectively embolised with Onyx 5 days prior to an extended thoracic aortic stent graft. Six pigs were used in this preliminary work. Four cases of paraplegia secondary to accidental migration of Onyx to the anterior spinal artery from the lumbar arteries are reported. Histological analysis confirmed severe spinal ischaemic injury and the presence of Onyx particles in the anterior spinal artery. DISCUSSION: Onyx is used for lumbar artery embolisation in type II endoleak treatment after endovascular aortic repair, and while migration in lumbar arteries is frequent, the risk of spinal cord ischaemia has never been described. The current study demonstrates the risk of paraplegia following Onyx migration to the anterior spinal artery from the lumbar artery in an experimental model. Thus, Onyx treatment for type II endoleaks from lumbar arteries should be used cautiously.

Embolization of ovarian vein for pelvic congestion syndrome with ethylene vinyl alcohol copolymer (Onyx®).

PURPOSE: To evaluate the safety and efficacy of pelvic embolization using ethylene vinyl alcohol copolymer (Onyx®) for pelvic congestion syndrome. MATERIAL AND METHODS: Between March 2012 to September 2016, 17 women (mean age, 44.7± 12.2 (SD) years; range: 34-71years) presenting with pelvic congestion syndrome were evaluated for transvenous embolization with Onyx®. Pelvic congestion syndrome was initially diagnosed by clinical examination and the results of transvaginal Doppler ultrasound and further confirmed by pelvic venography. Primary and secondary clinical efficacy was defined respectively by the resolution of the symptoms after embolization and at the end of the follow-up, irrespective to the number of embolization procedures. RESULTS: Technical efficacy of embolization was 100% with no significant complications during and after embolization. After a mean follow-up time of 24.2 months (range: 6-69months) a primary and secondary clinical efficacy of 76.4% (13/17 women) and 94.1% (16/17 women) respectively were observed. Four women (23.5%) underwent a second embolization procedure with one woman requiring a third embolization procedure. These additional embolization procedures were associated with direct puncture of vulvar varices for sclerotherapy in two women. Five women (29%) had recurrent symptoms 21 months post-treatment (7-42months). CONCLUSION: Pelvic embolization using ethylene vinyl alcohol copolymer (Onyx®) has a favorable clinical success for pelvic congestion syndrome.

Transcatheter arterial embolization with ethylene vinyl alcohol copolymer (Onyx) for the treatment of hemorrhage due to uterine arteriovenous malformations.

PURPOSE: The purpose of this study was to evaluate the effectiveness of ethylene vinyl alcohol copolymer (Onyx) as a single embolic agent for percutaneous arterial treatment of hemorrhage due to uterine arteriovenous malformations (AVMs). MATERIALS AND METHODS: Twelve women (mean age, 33 years) with metrorrhagia due to uterine AVMs who were treated by percutaneous arterial embolization using Onyx as a single embolic agent were retrospectively included. The diagnosis of uterine AVM was suggested by pelvic ultrasound and/or magnetic resonance imaging findings and further confirmed by angiography. Clinical files and angiographic examinations were reviewed for angiographic findings, technical and clinical success, procedure complication and further pregnancies. Clinical success was defined by absence of metrorrhagia at 1 month following embolization. RESULTS: Sixteen arterial embolization procedures were performed. Angiographically, 6 women had high flow AVM and 6 had low flow AVM. The rate of technical and clinical success was 92% (11/12 patients). One woman with early repeat hemorrhage underwent two embolization procedures and further hysterectomy. No severe complications were observed after embolization. Three women (3/12; 25%) became pregnant following embolization including one full term pregnancy. CONCLUSION: In women with metrorrhagia due to AVM, arterial embolization with Onyx is effective and safe. Additional research is needed to confirm the possibility of future pregnancy after Onyx embolization.

Varón de 59 años con insufi ciencia renal progresiva, seudotumor orbitario, derrame pericárdico y fenómeno de Raynaud / No disponible

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Correlation between strand asymmetry and phylogeny in mitochondrial DNA.

An evolutionary distance is introduced in order to propose an efficient and feasible procedure for phylogeny studies. Our analysis are based on the strand asymmetry property of mitochondrial DNA, but can be applied to other genomes. Comparison of our results with those reported in conventional phylogenetic trees, gives confidence about our approximation. Our findings support the hypotheses about the origin of the skew and its dependence upon evolutionary pressures, and improves previous efforts on using the strand asymmetry property of genomes for phylogeny inference. For the evolutionary distance introduced here, we observe that the more adequate technique for tree reconstructions correspond to an average link method which employs a sequential clustering algorithm.

Ole e 2 and Ole e 10: new clinical aspects and genetic restrictions in olive pollen allergy.

BACKGROUND: The clinical characteristics in olive pollen allergy are dependent on the antigenic load, the allergens profile, and the genetic restrictions. Our objective was to determine specific response pattern in Ole e 2 and Ole e 10 sensitization at those levels. METHODS: We studied 146 patients with seasonal rhinitis and/or asthma and positive prick test to Olea europaea pollen. IgE against Ole e 2 and Ole e 10 were detected by skin prick test and ELISA. HLA-DRB1 and HLA-DQB1 loci were typed by polymerase chain reaction sequence-specific primers method. RESULTS: A total of 102 (69.9%) and 79 (54.0%) patients showed significant IgE antibody response against Ole e 2 and Ole e 10, respectively. There was a significant association between Ole e 2 (OR 2.2, P = 0.04) and Ole e 10 reactivities (OR 2.8, P = 0.007) with asthma. In addition, total and specific IgE antibody levels significantly correlated with asthma (P < 0.05). Patients who reacted to both allergens reached the highest asthma risk factor (OR 4.3, P = 0.002). Phenotypic frequency of DR7 (OR 5.4, Pc = 0.003) and DQ2 (OR 3.6, Pc = 0.02) were increased in positive Ole e 2 patients compared with control subjects. DR2(15) phenotypic frequency was significantly increased (OR 5.6, Pc = 0.02) in positive Ole e 10 patients compared with control subjects. CONCLUSIONS: Our data suggest an association of Ole e 2 and Ole e 10 with bronchial asthma. Also, we found a genetic control of Ole e 2 and Ole e 10 IgE-specific responses that could be relevant to clinical disease in olive pollen allergy.

Structural determinants outside the PXDLS sequence affect the interaction of adenovirus E1A, C-terminal interacting protein and Drosophila repressors with C-terminal binding protein.

C-Terminal binding protein (CtBP) interacts with a highly conserved amino acid motif (PXDLS) at the C terminus of adenovirus early region 1A (AdE1A) protein. This amino acid sequence has recently been demonstrated in the mammalian protein C-terminal interacting protein (CtIP) and a number of Drosophila repressors including Snail, Knirps and Hairy. In the study described here we have examined the structures of synthetic peptides identical to the CtBP binding sites on these proteins using NMR spectroscopy. It has been shown that peptides identical to the CtBP binding site in CtIP and at the N terminus of Snail form a series of beta-turns similar to those seen in AdE1A. The PXDLS motif towards the C terminus of Snail forms an alpha-helix. However, the motifs in Knirps and Hairy did not adopt well-defined structures in TFE/water mixtures as shown by the absence of medium range NOEs and a high proportion of signal overlap. The affinities of peptides for Drosophila and mammalian CtBP were compared using enzyme-linked immunosorbent assay. CtIP, Snail (N-terminal peptide) and Knirps peptides all bind to mammalian CtBP with high affinity (K(i) of 1.04, 1.34 and 0.52 microM, respectively). However, different effects were observed with dCtBP, most notably the affinity for the Snail (N-terminal peptide) and Knirps peptides were markedly reduced (K(i) of 332 and 56 microM, respectively) whilst the Hairy peptide bound much more strongly (K(i) for dCtBP of 6.22 compared to 133 microM for hCtBP). In addition we have shown that peptides containing identical PXDLS motifs but with different N and C terminal sequences have appreciably different affinities for mammalian CtBP and different structures in solution. We conclude that the factors governing the interactions of CtBPs with partner proteins are more complex than simple possession of the PXDLS motif. In particular the overall secondary structures and amino acid side chains in the binding sites of partner proteins are of importance as well as possible global structural effects in both members of the complex. These data are considered evidence for a multiplicity of CtBPs and partner proteins in the cell.

Structural determinants in adenovirus 12 E1A involved in the interaction with C-terminal binding protein 1.

The interaction between the C-terminal binding protein 1 (CtBP-1) and purified Ad12 E1A protein has been examined through the use of a combination of biophysical techniques. A fragment equivalent to the 77 C-terminal amino acids of Ad12 E1A (Ad12 77-a.a. E1A) was generated by limited proteolysis of Ad12 266-a.a. E1A at Phe(187) and/or Tyr(189) using chymotrypsin. The impact of deletion of the 189 N-terminal amino acids from E1A on the equilibrium dissociation constant K(d) for binding to CtBP was assessed using ELISA in vitro binding assays and intrinsic fluorescence spectroscopy. Values of K(d) of 4.0 and 38 nM were determined for full-length and truncated forms of E1A, respectively. Circular dichroism spectroscopic studies revealed that the conformation adopted by these polypeptides is dependent on the surrounding environment, which is predominately randomly folded when free in solution, but adopting a more ordered alpha-helical secondary structure in the presence of trifluoroethanol. Using nuclear magnetic resonance (NMR) spectroscopy to examine the interaction between Ad E1A and CtBP it was observed that the chemical shift positions of individual backbone amide nitrogen atoms were well resolved in (15)N-(1)H-HSQC NMR spectra performed on samples of isotopically (15)N-labeled Ad12 77-a.a. E1A. In the presence of CtBP, signals of backbone amide nitrogen atoms displayed increased linewidth consistent with an increase in molecular mass upon binding CtBP. In addition, some signals that have been attributed to Val(254/256) and Leu(259), and reside within the binding site for CtBP on E1A, are shifted in the (15)N- and/or (1)H-dimensions, defining specific contacts between E1A and CtBP. These data suggest that structural determinants in the C-terminal PXDLS binding motif in the rest of exon 2 and in exon 1 all contribute to optimizing the conformation of the binding site on Ad12 E1A for CtBP. However, no interaction was observed between CtBP and truncated Ad12 E1A, which no longer contained the C-terminal binding motif.

Nonlinear modeling technique for the analysis of DNA chains.

Using a simple computational procedure, we examine DNA chains from different species in order to prove their nonlinear deterministic structures. This procedure applies a nonlinear modeling technique based upon quantitative comparison of the neighborhoods from similar DNA subsegments of size d. Our results reveal that noncoding regions exhibit a deterministic signature at sizes larger than a characteristic dimension d(c). Applications to evolutionary categories and recognition of different DNA regions are discussed.

CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells.

A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.

Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients.

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.