Adventitial Myofibroblasts Play no Major Role in Neointima Formation After Angioplasty

Abstract

Objective—Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts. Design—Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for (X-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype).

Results—Adventitial cells became transiently actinpositive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82 ± 10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen.

Conclusion—At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.     

Adéquation en dialyse péritonéale : mise au point

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the “corner-stone” of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.     

Management of midline dural sinus malformations and review of the literature

Purpose

Dural sinus malformations (DSMs) are rare pediatric vascular lesions that have variable presentations and outcomes. We present three cases of midline DSMs and discuss the treatment strategy employed for each lesion. A review of the literature was completed to summarize current literature and treatment practices.

Methods

A retrospective review of the electronic medical record and all available imaging studies was performed for each of our patients.

Results

Patient 1 had a prenatally diagnosed DSM which decreased in size despite no intervention. She was born without complication and continues to do well at 15 months of age. Patient 2 presented 2 weeks after birth with cardiac failure, intracranial hemorrhage, and seizures and imaging showed a large midline DSM with multiple high-flow shunts. She required multiple endovascular embolizations with complete occlusion of the lesion. At her 3-year follow-up, she was neurologically normal. The third patient was diagnosed prenatally with an enlarging DSM. Multiple endovascular embolizations, surgical decompression, cranial expansion, and CSF diversion were required for treatment. At her 2.5-year follow-up, she was meeting developmental milestones, with some motor delay.

Conclusion

Early diagnosis and treatment, if necessary, of DSMs are critical to prevent cardiac failure or parenchymal injury from chronic venous hypertension. Management should be decided on individual case basis depending on the angioarchitecture and progression of the lesion and can involve observation, endovascular embolization, surgical interventions, or a combination of treatments. A personalized approach to treating these variable lesions can be associated with good outcomes.

     

Expression of minichromosome maintenance MCM6 protein in meningiomas is strongly correlated with histologic grade and clinical outcome

The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). Histologic grading and mitotic index were correlated with progression-free survival (P=0.010 and P=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (P<0.001), Ki-67 (P=0.003), and PHH3 (P=0.037) but not for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with a high risk of recurrence.     

Discitis and sacroiliitis diagnosed 15 years after iatrogenic Mycobacterium xenopi inoculation

A patient was diagnosed with discitis and sacroiliitis due to Mycobacterium xenopi. He had a history of percutaneous nucleotomy performed 15 years earlier (in 1992) at the Clinique du Sport, Paris, France, during an outbreak of nosocomial M. xenopi infection at that institution. In 1997, magnetic resonance imaging performed as part of the routine follow-up program for patients who had surgery at the Clinique du Sport during the outbreak was not interpreted as indicating discitis; this assessment was confirmed by our review of the images. Bone and joint infections due to atypical mycobacteria are rare and can develop very slowly. To our knowledge, this is the first reported case of M. xenopi discitis with secondary extension to the sacroiliac joint in an immunocompetent patient.     

Recent advances in the surgical management of herniated thoracic discs

Symptomatic thoracic disc herniation is an uncommon entity, without characteristic clinical presentation, and remains a surgical challenge. The initial surgical procedure for thoracic disc herniations was laminectomy with discectomy. The high rate of post-operative neurological deficit makes laminectomy now unacceptable for thoracic disc herniation treatment. Transthoracic, transpedicular, and posterolateral (costotransversectomy) approaches of thoracic discectomy have been used successfully. This review comprises eight papers. Six of them report retrospective series of patients with symptomatic thoracic disc herniations treated by the transpedicular approach (Le Roux, 20 patients), the transfacet pediclesparing approach (Stillermann, 6 patients; Ridenour, 12 patients), modified costotransversectomy (Simpson, 21 patients; Ridenour, 15 patients), the lateral extracavitary approach (Delfini, 20 patients), and the anterior cervical approach (Rossiti, 1 patient with T1-T2 disc). Comparison of the results of the posterolateral and anterolateral approaches does not show clear evidence of better neurological results or pain relief with one type of approach rather than another. Endoscopic or video-assisted techniques have been used recently (Rosenthal, 1 patient; Hae-Dong Jho, 2 patients) and seem attractive.     

Evidence of trochlear dysplasia in patellofemoral arthroplasty designs

Purpose

The design of the trochlear compartment is crucial in patellofemoral arthroplasty (PFA), because 78 % of patients with isolated patellofemoral arthritis present concomitant trochlear dysplasia with patellar maltracking and therefore remain predisposed to post-operative patellar subluxation and dislocation. The study investigated whether current PFA implants are designed with anatomic trochlear parameters such as the sulcus angle, lateral facet height and groove orientation.

Methods

Five trochlear components of commercially available PFA implants were scanned, and the generated three-dimensional surfaces were measured using engineering design software. The mediolateral trochlear profiles were plotted at various flexion angles (0°, 15°, 30° and 45°) to deduce the following variables: sulcus angle, height of lateral facet and trochlear groove orientation.

Results

Four specimens had sulcus angle >144° in the 45° of flexion, and all five specimens had sulcus angle >143° in 30° of flexion. Three specimens had a facet <5 mm high through the entire range of early flexion (0°–30°), and two specimens had a facet <5 mm high beyond early flexion (30°–45°). The trochlear groove was oriented laterally in all specimens (range 1.6°–13.5°).

Conclusion

Current PFA trochlear components are not always designed with anatomic parameters, and some models exhibit characteristics of trochlear dysplasia. Surgeons are therefore advised to implant components with a deep sulcus, particularly in patients with history of patellofemoral disorders, and to adapt the surgical technique and extensor mechanism if the component implanted has a shallow sulcus, to ensure normal patellar tracking.

Level of evidence

III.     

Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis‐susceptible sites in foals revealed by SWI 3T MRI

Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non‐invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility‐weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) day‐old foals, with minimal joint loading after birth, was performed. SWI and 3D images revealed the EGC vascular architecture without a contrast agent, and matched histologic observations. No vascular lesions were identified. There was no difference in the vascular density and architecture between control and OC specimens, but a striking difference in vascular pattern was seen at the OC‐predilected site in the lateral ridge of the trochlea in all specimens, when compared to the medial ridge of the trochlea, where OC lesions are rarely observed. This site was less ossified with more perichondrial vessels not yet bridging with the subchondral bone. Furthermore, the mean vascular density of all specimens was significantly higher at this site. We speculate that joint morphology and focal internal trauma on this site with a unique vascular architecture may trigger ischemic events at this site. SWI permitted visualization of EGC in young foals with a clinical 3T MRI and paves the way for non‐destructive longitudinal studies to improve understanding of OC in all species. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1539–1546, 2016.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.