Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Three-year outcomes of percutaneous coronary intervention with next-generation zotarolimus-eluting stents for de novo coronary bifurcation lesions.

AIMS To investigate the outcomes of percutaneous coronary intervention (PCI) in bifurcation versus non-bifurcation lesions using the next-generation Resolute zotarolimus-eluting stent (R-ZES). METHODS AND RESULTS We analyzed 3-year pooled data from the RESOLUTE All-Comers trial and the RESOLUTE International registry. The R-ZES was used in 2772 non-bifurcation lesion patients and 703 bifurcation lesion patients, of which 482 were treated with a simple-stent technique (1 stent used to treat the bifurcation lesion) and 221 with a complex bifurcation technique (2 or more stents used). The primary endpoint was 3-year target lesion failure (TLF, defined as the composite of death from cardiac causes, target vessel myocardial infarction, or clinically-indicated target lesion revascularization [TLR]), and was 13.3% in bifurcation vs 11.3% in non-bifurcation lesion patients (adjusted P=.06). Landmark analysis revealed that this difference was driven by differences in the first 30 days between bifurcation vs non-bifurcation lesions (TLF, 6.6% vs 2.7%, respectively; adjusted P<.001), which included significant differences in each component of TLF and in-stent thrombosis. Between 31 days and 3 years, TLF, its components, and stent thrombosis did not differ significantly between bifurcation lesions and non-bifurcation lesions (TLF, 7.7% vs 9.0%, respectively; adjusted P=.50). CONCLUSION The 3-year risk of TLF following PCI with R-ZES in bifurcation lesions was not significantly different from non-bifurcation lesions. However, there was an increased risk associated with bifurcation lesions during the first 30 days; beyond 30 days, bifurcation lesions and non-bifurcation lesions yielded similar 3-year outcomes.

Adverse effects of fillers and their histopathology.

Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions.

OBJECTIVES Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. MATERIALS AND METHODS Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. RESULTS A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. CONCLUSION Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. KEY POINTS • MR quantification is feasible for characterization of different stages of myocardial infarction. • The results provide the base for computer-aided MRI cardiac infarction diagnosis. • Diagnostic criteria may also be applied for living patients.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

Late diagnosis of fucosidosis in a child with progressive fixed dystonia, bilateral pallidal lesions and red spots on the skin

Fucosidosis is a rare lysosomal storage disease. A 14-year-old girl is presented, with recurrent infections, progressive dystonic movement disorder and mental retardation with onset in early childhood. The clinical picture was also marked by mild morphologic features, but absent dysostosis multiplex and organomegaly. MRI images at 6.5 years of age were reminiscent of pallidal iron deposition ("eye-of-the-tiger" sign) seen in neurodegeneration with brain iron accumulation (NBIA) disorders. Progressively spreading angiokeratoma corporis diffusum led to the correct diagnosis. This case extends the scope of clinical and neuroradiological manifestations of fucosidosis.

Response to neoadjuvant treatment of invasive ductal breast carcinomas including outcome evaluation: MRI analysis by an automatic CAD system in comparison to visual evaluation

BACKGROUND The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND METHODS Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases. RESULTS Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually). CONCLUSIONS In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

Dislocability of localization devices for nonpalpable breast lesions: experimental results

Purpose. For accurate resection of nonpalpable malignant breast lesions with a tumor-free resection rim, an exact and stable wire localization is essential. We tested the resistance towards traction force of different localization devices used in our clinic for breast lesions in two types of tissue. Materials and Methods. Eight different commercially available hook-wire devices were examined for resistance towards traction force using an analogue spring scale. Results. Most systems showed a high level of movement already under small traction force. Retractable systems with round hooks such as the Bard DuaLok , the Fil d'Ariane, and the RPLN Breast Localization Device withstood less traction force than the other systems. However, the Bard DuaLok system was very resistant towards a small traction force of 50 g when compared to the other systems. The Ultrawire Breast Localization Device withstood the most traction force in softer tissue and Kopans Breast Lesion Localization Needle withstood the most force in harder tissue. Conclusion. The Ultrawire Breast Localization Device and Kopans Breast Lesion Localization Needle withstood the most traction force. In general retractable systems withstand less traction force than nonretractable systems.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants.

BACKGROUND AND PURPOSE To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

A computer-assisted microscopic analysis of bone tissue developed inside a polyactive plymer implanted into an equine articular surface

One of the most promising applications for the restoration of small or moderately sized focal articular lesions is mosaicplasty (MP). Although recurrent hemarthrosis is a rare complication after MP, recently, various strategies have been designed to find an effective filling material to prevent postoperative bleeding from the donor site. The porous biodegradable polymer Polyactive (PA; a polyethylene glycol terephthalate - polybutylene terephthalate copolymer) represents a promising solution in this respect. A histological evaluation of the longterm PA-filled donor sites obtained from 10 experimental horses was performed. In this study, attention was primarily focused on the bone tissue developed in the plug. A computer-assisted image analysis and quantitative polarized light microscopic measurements of decalcified, longitudinally sectioned, dimethylmethylene blue (DMMB)- and picrosirius red (PS) stained sections revealed that the coverage area of the bone trabecules in the PA-filled donor tunnels was substantially (25%) enlarged compared to the neighboring cancellous bone. For this quantification, identical ROIs (regions of interest) were used and compared. The birefringence retardation values were also measured with a polarized light microscope using monochromatic light. Identical retardation values could be recorded from the bone trabeculae developed in the PA and in the neighboring bone, which indicates that the collagen orientation pattern does not differ significantly among these bone trabecules. Based on our new data, we speculate that PA promotes bone formation, and some of the currently identified degradation products of PA may enhance osteo-conduction and osteoinduction inside the donor canal.

The effect of RNA base lesions on mRNA translation

The biological effect of oxidatively damaged RNA, unlike oxidatively damaged DNA, has rarely been investigated, although it poses a threat to any living cell. Here we report on the effect of the commonly known RNA base-lesions 8-oxo-rG, 8-oxo-rA, ε-rC, ε-rA, 5-HO-rC, 5-HO-rU and the RNA abasic site (rAS) on ribosomal translation. To this end we have developed an in vitro translation assay based on the mRNA display methodology. A short synthetic mRNA construct containing the base lesion in a predefined position of the open reading frame was 32P-labeled at the 5′-end and equipped with a puromycin unit at the 3′-end. Upon in vitro translation in rabbit reticulocyte lysates, the encoded peptide chain is transferred to the puromycin unit and the products analyzed by gel electrophoresis. Alternatively, the unlabeled mRNA construct was used and incubated with 35S-methionine to prove peptide elongation of the message. We find that all base-lesions interfere substantially with ribosomal translation. We identified two classes, the first containing modifications at the base coding edge (ε-rC, ε-rA and rAS) which completely abolish peptide synthesis at the site of modification, and the second consisting of 8-oxo-rG, 8-oxo-rA, 5-HO-rC and 5-HO-rU that significantly retard full-length peptide synthesis, leading to some abortive peptides at the site of modification.

Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment.

BACKGROUND AND PURPOSE Lesion volume on diffusion-weighted magnetic resonance imaging (DWI) before acute stroke therapy is a predictor of outcome. Therefore, patients with large volumes are often excluded from therapy. The aim of this study was to analyze the impact of endovascular treatment in patients with large DWI lesion volumes (>70 mL). METHODS Three hundred seventy-two patients with middle cerebral or internal carotid artery occlusions examined with magnetic resonance imaging before treatment since 2004 were included. Baseline data and 3 months outcome were recorded prospectively. DWI lesion volumes were measured semiautomatically. RESULTS One hundred five patients had lesions >70 mL. Overall, the volume of DWI lesions was an independent predictor of unfavorable outcome, survival, and symptomatic intracerebral hemorrhage (P<0.001 each). In patients with DWI lesions >70 mL, 11 of 31 (35.5%) reached favorable outcome (modified Rankin scale score, 0-2) after thrombolysis in cerebral infarction 2b-3 reperfusion in contrast to 3 of 35 (8.6%) after thrombolysis in cerebral infarction 0-2a reperfusion (P=0.014). Reperfusion success, patient age, and DWI lesion volume were independent predictors of outcome in patients with DWI lesions >70 mL. Thirteen of 66 (19.7%) patients with lesions >70 mL had symptomatic intracerebral hemorrhage with a trend for reduced risk with avoidance of thrombolytic agents. CONCLUSIONS There was a growing risk for poor outcome and symptomatic intracerebral hemorrhage with increasing pretreatment DWI lesion volumes. Nevertheless, favorable outcome was achieved in every third patient with DWI lesions >70 mL after successful endovascular reperfusion, whereas after poor or failed reperfusion, outcome was favorable in only every 12th patient. Therefore, endovascular treatment might be considered in patients with large DWI lesions, especially in younger patients.

TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.

Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.

Accuracy of cartilage-specific 3-Tesla 3D-DESS magnetic resonance imaging in the diagnosis of chondral lesions: comparison with knee arthroscopy

BACKGROUND Arthroscopy is considered as "the gold standard" for the diagnosis of traumatic intraarticular knee lesions. However, recent developments in magnetic resonance imaging (MRI) now offer good opportunities for the indirect assessment of the integrity and structural changes of the knee articular cartilage. The study was to investigate whether cartilage-specific sequences on a 3-Tesla MRI provide accurate assessment for the detection of cartilage defects. METHODS A 3-Tesla (3-T) MRI combined with three-dimensional double-echo steady-state (3D-DESS) cartilage specific sequences was performed on 210 patients with knee pain prior to knee arthroscopy. Sensitivity, specificity, and positive and negative predictive values of magnetic resonance imaging were calculated and correlated to the arthroscopic findings of cartilaginous lesions. Lesions were classified using the modified Outerbridge classification. RESULTS For the 210 patients (1260 cartilage surfaces: patella, trochlea, medial femoral condyle, medial tibia, lateral femoral condyle, lateral tibia) evaluated, the sensitivities, specificities, positive predictive values, and negative predictive values of 3-T MRI were 83.3, 99.8, 84.4, and 99.8 %, respectively, for the detection of grade IV lesions; 74.1, 99.6, 85.2, and 99.3 %, respectively, for grade III lesions; 67.9, 99.2, 76.6, and 98.2 %, respectively, for grade II lesions; and 8.8, 99.5, 80, and 92 %, respectively, for grade I lesions. CONCLUSIONS For grade III and IV lesions, 3-T MRI combined with 3D-DESS cartilage-specific sequences represents an accurate diagnostic tool. For grade II lesions, the technique demonstrates moderate sensitivity, while for grade I lesions, the sensitivity is limited to provide reliable diagnosis compared to knee arthroscopy.