Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes

BACKGROUND: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. AIMS: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. METHODS AND RESULTS: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. CONCLUSIONS: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation.     

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres

Background

Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies.

Objectives

To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary.

Methods

Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures.

Results

Two-hundred patients were involved (females 32 %) with a mean age of 51 (SD 13) years, 103 (52 %) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86 %. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups.

Conclusions

Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

     

The Role of 3-D Endorectal Ultrasound in Rectal Cancer: Our Experience

In the last 20 years, endorectal ultrasound (ERUS) has been one of the main diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate modality for evaluating local invasion of rectal carcinoma into the rectal wall layers (T category). Adding the three-dimensional modality (3-D) increases the capabilities of this diagnostic tool in rectal cancer patients. We review the literature and report our experience in preoperative 3-D ERUS in rectal cancer staging. In the group of 71 patients, the staging of preoperative 3-D endorectal ultrasonography was compared with the postoperative morphologic examination. Three-dimensional ERUS preoperative staging was confirmed with morphologic evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4, 100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4, 98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2, 94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was 2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4% (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D ERUS has the potential to become the diagnostic modality of choice for the preoperative staging of rectal cancer.Key words: Three-dimensional endorectal ultrasound, Rectal cancerEndorectal ultrasound (ERUS) has been used as a diagnostic tool for evaluation and staging of rectal cancer since the 1980s.¹ According to the literature, in studies with more than 50 patients included, an overall accuracy of approximately 81.8% was reported.² Most of the studies present data between 85% and 95%, but in the studies with more than 200 patients, the accuracy rates are relatively lower—63.3% and 69%, respectively.^3,4 A common disadvantage of ERUS and magnetic resonance imaging (MRI) is the overstaging of T2 tumors owing to an irregular outer rectal wall resulting from transmural tumor extension or inflammation around the tumor. Another challenge for the ERUS, and especially the rigid probes, are the locally advanced, stenotic tumors, where the probe may not be able to pass above the lesion.⁵ The nodal staging accuracy of ERUS ranges from 70% to 75%.^1,5,6 The metastatic lymph nodes are distinguished by hypoechoic appearance, round shape, peritumoral location, and size >5 mm.^7,8 Lymph nodes >5 mm have a 50% to 70% chance of being malignant, while those <4 mm have only a 20% chance.^9,10 A new modality of endorectal ultrasound represents a three-dimensional (3-D) ERUS that provides better visual images of the tumor volume and spatial relations to the adjacent organs and structures, even better than those of MRI, which leads to better diagnostic accuracy than MRI and standard ERUS.^11–15 The unique 3-D–ERUS longitudinal scan can precisely assess the tumor size and location.¹⁶ The most important feature of this upgraded modality is the ability to reduce interpreter errors and offer potential predictive value. Three-dimensional ERUS provides the possibility to distinguish blood vessels from lymph nodes and allow precise fine needle aspiration (FNA) biopsies.^13,17 The infiltration of circumferential margin has been proven to correlate with T category, lymph node metastasis histologic tumor differentiation, and lymphovascular invasion.^13,17 Three-dimensional ERUS gives the possibility of multiplane evaluation of the tumor, allowing visualization of more subtle changes in the tumor characteristics and therefore better T and N categorizing.¹⁸ A review of 86 patients who underwent standard 3-D ERUS, ERUS and 4-channel detector computed tomography (CT) demonstrated T-category accuracy of 78%, 69%, and 57%, respectively.¹⁹ After analysis of the examiner''s error, the accuracy of 3-D ERUS for T category has reached 91% for 3-D ERUS and 88% for standard ERUS, and the N category accuracy improved to 90% and 76%, respectively. Also, ERUS can be used for diagnosis of premalignant lesions such as adenomas and polyps.²⁰ The main goal is to properly identify any chance of tumor invasion in the primary lesion and involvement of the surrounding lymph nodes in case the absence of those alarming characteristics allows for endoscopic resection of the lesion. Using higher-resolution probes, ERUS can distinguish T0 from T1 lesions. According to a meta-analysis of 258 biopsy-negative tumors, ERUS identified tumor mass in 81% of the 24 lesions, which were found to be invasive tumors on morphologic examination.²⁰ Another series of 60 patients with pT0/pT1 lesions demonstrated sensitivity and specificity of ERUS 89% and 88%, respectively.²¹ As with MRI, 3-D ERUS could provide an evaluation of the mesorectal fascia.^14,22The reported data lead to the position that 3-D ERUS combines the high-resolution images of the rectal wall and cost-effectiveness of standard ERUS with the multiplanar and stereoscopic imaging capabilities of MRI. Three-dimensional ERUS may be the future premier imaging modality used in rectal cancer management.     

Enhancement in sustained friction and wear resistance of nanoporous aluminum oxide films obtained by controlled electrochemical oxidation process

The primary purpose of this study is to investigate the effect of the electrochemical parameters required in the anodic oxidation process on the friction and wear resistance of the obtained nanoporous aluminum oxide films. The wear resistance of the aluminum oxide films and the electrochemically polished Al1050 alloy were tested using a ball-on-disc tribometer having a corundum ball as counterbody in dry conditions. The friction coefficient graphs were recorded during wear tests at a 5 N normal force simulating the application of nanoporous aluminum oxide films in industrial areas requesting moderate wear resistance. The wear tracks formed on the tested surfaces were analyzed ex situ both qualitatively and quantitatively. Higher wear resistance is showed by nanoporous aluminum oxide films as compared with electro polished Al1050 alloy substrate.

The primary purpose of this study is to investigate the effect of the electrochemical parameters required in the anodic oxidation process on the friction and wear resistance of the obtained nanoporous aluminum oxide films.     

Predicting effective connectivity from resting‐state networks in healthy elderly and patients with prodromal Alzheimer's disease

Using functional neuroimaging techniques two aspects of functional integration in the human brain have been investigated, functional connectivity and effective connectivity. In this study we examined both connectivity types in parallel within an executive attention network during rest and while performing an attention task. We analyzed the predictive value of resting‐state functional connectivity on task‐induced effective connectivity in patients with prodromal Alzheimer's disease (AD) and healthy elderly. We found that in healthy elderly, functional connectivity was a significant predictor for effective connectivity, however, it was frequency‐specific. Effective top‐down connectivity emerging from prefrontal areas was related with higher frequencies of functional connectivity (e.g., 0.08–0.15 Hz), in contrast to effective bottom‐up connectivity going to prefrontal areas, which was related to lower frequencies of functional connectivity (e.g., 0.001–0.03 Hz). In patients, the prediction of effective connectivity by functional connectivity was disturbed. We conclude that functional connectivity and effective connectivity are interrelated in healthy brains but this relationship is aberrant in very early AD. Hum Brain Mapp 35:954–963, 2014. © 2013 Wiley Periodicals, Inc.     

The Contribution of the Left Phrenic Nerve to Innervation of the Esophagogastric Junction

The contribution of the left phrenic nerve to innervation of the esophagogastric junction. The esophagogastric junction is part of the barrier preventing gastroesophageal reflux. We have investigated the contribution of the phrenic nerves to innervation of the esophagogastric junction in humans and piglets by dissecting 30 embalmed human specimens and 14 piglets. Samples were microdissected and nerves were stained and examined by light and electron microscopy. In 76.6% of the human specimens, the left phrenic nerve participated in the innervation of the esophagogastric junction by forming a neural network together with the celiac plexus (46.6%) or by sending off a distinct phrenic branch, which joined the anterior vagal trunk (20%). Distinct left phrenic branches were always accompanied by small branches of the left inferior phrenic artery. In 10% there were indirect connections with a distinct phrenic nerve branch joining the celiac ganglion, from which celiac plexus branches to the esophagogastric junction emerged. Morphological examination of phrenic branches revealed strong similarities to autonomic celiac plexus branches. There was no contribution of the left phrenic nerve or accompanying arteries from the caudal phrenic artery in any of the piglets. The right phrenic nerve made no contribution in any of the human or piglet samples. We conclude that the left phrenic nerve in humans contributes to the innervation of the esophagogastric junction by providing ancillary autonomic nerve fibers. Experimental studies of the innervation in pigs should consider that neither of the phrenic nerves was found to contribute. Clin. Anat. 33:265–274, 2020. © 2019 Wiley Periodicals, Inc.     

The Radioulnar Distance at the Level of the Radial Tuberosity

Ruptures of the distal biceps brachii tendon are generally treated operatively due to their loss of supination and flexion force. A mechanical impingement at the insertion of the tendon at the radial tuberosity is discussed to play a role in the etiology of this injury. The aim of this study was to present a detailed, three-dimensional anatomical analysis of the radioulnar space at the radial tuberosity. A total of 166 imprints of the radioulnar space in neutral rotation and pronation from 84 cadaveric specimens of both arms using silicone impression material were produced for this study. Imprints were cut in slices of 3 mm and digitally measured after picture acquisition using a high-resolution digital camera. Distances were grouped into a proximal, central, and distal groups and used for correlation to morphometric data at the elbow (radial head diameter, ulna and radius length) as well as volume calculation. The mean radioulnar distance was 8.8 ± 4.0 mm in neutral rotation and 7.8 ± 3.9 mm in pronation. In pronation, the central zone was the smallest whereas in neutral rotation the proximal zone was the smallest. The volume of the radioulnar space did not reduce significantly during pronation. Little space is provided for the insertion of the distal biceps brachii tendon especially during pronation. This could play a role in the etiology of distal biceps brachii tendon ruptures and should be considered in the fixation after rupture of the tendon. Clin. Anat., 33:661–666, 2020. © 2019 Wiley Periodicals, Inc.