High iliac calcium score is associated with increased severity and complexity of peripheral arterial disease and predicts global atherosclerotic burden.

BACKGROUND: The role of vascular calcifications in iliac arteries for predicting global atherosclerotic burden in still unknown. The aim of this study was to investigate whether iliac calcium score (ICS), a new computed tomographic angiography (CTA) derived biomarker of vascular calcification, can predict the severity and complexity of peripheral arterial disease (PAD) as well as the global atherosclerotic burden. PATIENTS AND METHODS: This was a single centre, non-randomized, observational prospective study on 84 consecutive patients with symptomatic peripheral arterial disease, undergoing peripheral CTA examination of the lower limbs, divided into high (n = 42) and low ICS (n = 42) groups with a median value for ICS of 3934 HU. RESULTS: Patients with high ICS were significantly older (66.2 ± 8.0 vs. 62.8 ± 11.2, p < 0.0001) and were more frequently diabetic (61.9 vs. 38.1 %, p = 0.04). ICS was significantly higher in patients with Rutherford stage 5-6 vs. 1-2 (p = 0.03) and in TASC D or TASC C vs. TASC B class (p = 0.01). Mean iliac intima-media thickness (i-IMT) was significantly higher in the high ICS group compared to the low ICS group (1.3 ± 0.2 vs. 0.9 ± 0.2, p < 0.0001). Linear regression analysis demonstrated a very good correlation between ICS and i-IMT (r = 0.59, p < 0.0001 for right, r = 0.57, p < 0.0001 for left and r = 0.67, p < 0.0001 for both iliac arteries averaged). Patients with high ICS presented a significantly lower left ventricular ejection fraction compared to those with low ICS (45.3 ± 4.3 vs. 53.8 ± 4.8, p < 0.0001). Linear regression analysis demonstrated significant inverse correlation between ICS and left ventricular EF (r = -0.54, p < 0.0001). CONCLUSIONS: Increased values of ICS, a new CTA marker of vascular calcification, are associated with a higher severity and complexity of PAD and a more depressed left ventricular function. High ICS values are also associated with increased i-IMT. Both can represent new surrogate markers of an increased atherosclerotic burden.

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance.

We have reviewed the development and current status of therapies based on exposure to non-ionizing radiation (with a photon energy less than 10 eV) aimed at suppressing the venous neointimal hyperplasia, and consequentially at avoiding stenosis in arteriovenous grafts. Due to the drawbacks associated with the medical use of ionizing radiation, prominently the radiation-induced cardiovascular disease, the availability of procedures using non-ionizing radiation is becoming a noteworthy objective for the current research. Further, the focus of the review was the use of such procedures for improving the vascular access function and assuring the clinical success of arteriovenous fistulae in hemodialysis patients. Following a brief discussion of the physical principles underlying radiotherapy, the current methods based on non-ionizing radiation, either in use or under development, were described in detail. There are currently five such techniques, including photodynamic therapy (PDT), far-infrared therapy, photochemical tissue passivation (PTP), Alucent vascular scaffolding, and adventitial photocrosslinking. The last three are contingent on the mechanical stiffening achievable by the exogenous photochemical crosslinking of tissular collagen, a process that leads to the decrease of venous compliance. As there are conflicting opinions on the role of compliance mismatch between arterial and venous conduits in a graft, this aspect was also considered in our review.

Inflammation, Microcalcification, and Increased Expression of Osteopontin Are Histological Hallmarks of Plaque Vulnerability in Patients with Advanced Carotid Artery Stenosis.

BACKGROUND: severe carotid artery stenosis is a major cause of ischemic stroke and consequent neurological deficits. The most important steps of atherosclerotic plaque development, leading to carotid stenosis, are well-known; however, their exact timeline and intricate causal relationships need to be more characterized. METHODS: in a cohort of 119 patients, who underwent carotid endarterectomy, we studied the histological correlations between arterial calcification patterns and localization, the presence of the inflammatory infiltrate and osteopontin expression, with ulceration, thrombosis, and intra-plaque hemorrhage, as direct signs of vulnerability. RESULTS: in patients with an inflammatory infiltrate, aphasia was more prevalent, and microcalcification, superficial calcification, and high-grade osteopontin expression were characteristic. Higher osteopontin expression was also correlated with the presence of a lipid core. Inflammation and microcalcification were significantly associated with plaque ulceration in logistic regression models; furthermore, ulceration and the inflammatory infiltrate were significant determinants of atherothrombosis. CONCLUSION: our results bring histological evidence for the critically important role of microcalcification and inflammatory cell invasion in the formation and destabilization of advanced carotid plaques. In addition, as a calcification organizer, high-grade osteopontin expression is associated with ulceration, the presence of a large lipid core, and may also have an intrinsic role in plaque progression.

Intraplaque Neovascularization, CD68+ and iNOS2+ Macrophage Infiltrate Intensity Are Associated with Atherothrombosis and Intraplaque Hemorrhage in Severe Carotid Atherosclerosis.

BACKGROUND: Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. METHODS: Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. RESULTS: Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). CONCLUSIONS: Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

A single-center prospective study on the efficiency of negative pressure wound therapy versus conventional wound therapy in the postoperative management of devitalized and infected wounds.

INTRODUCTION: In this study, we aim to present the benefits of using negative pressure wound therapy, particularly with respect to the speed up of recovery time of devitalized and infected post-operative wounds, cost-effectiveness of local healing, pain relief during treatment, and returning to work and resuming normal daily activities at an earlier time. MATERIALS AND METHODS: This was a prospective study performed in General Surgery Clinic, between 2016-2018. The study comprised 67 patients divided into two groups: A (29 patients who underwent negative pressure wound therapy) and B (38 patients who underwent conventional wound therapy). RESULTS: The average age of patients included in group A was 64.2 ± 12.3 years and in group B, 63.2 ± 9.7 years (p=0.440). The wounds were located on the foot, thigh, abdomen, and other areas, and the average length of stay in hospital was 33 ± 18 days for group A versus 17 ± 14 days for group B (p=0.042) but with an average local healing time of 12 ± 5 days in group A versus 44 ± 17 days in group B (p<0.001). The average cost of hospitalization was higher in group A: 17,868 ± 9,560 RON (3,834 ± 2,051 euros) compared to group B: 6,025 ± 4,137 RON (1,292 ± 887 euros) (p=0.443) but the average cost of local healing was lower in group A: 5,437 ± 2,238 RON (1,166 ± 480 euro) compared to group B: 6,840 ± 3,520 RON (1,467 ± 755 euro) (p=0.005). CONCLUSIONS: The treatment of devitalized and infected post-operative wounds by using negative pressure wound therapy reduces local and complete healing time by approximately 30%, local healing costs by 26%, and allows better pain management during treatment with minimal complications. KEY WORDS: Negative pressure wound Therapy, Conventional wound therapy, Local healing, average cost.

Case Report: Gigantic Arteriovenous Femoral Fistula Following Cardiac Artery Catheterization.

PURPOSE: To present the case of a patient with a 9-mm iatrogenic fistula between a branch of the right profunda femoris artery, aneurysmally dilated at ~1.851cm, and the right femoral vein, successfully treated with open surgical ligation. CASE REPORT: A 70-years-old female was referred to the Vascular Surgery Clinic due to worsening cardiac failure symptoms during the previous year. The medical history included a diagnostic cardiac artery catheterism through a Seldinger technique one year and a half ago. A recent ultrasound described velocities characteristic for a high flow arteriovenous communication in the right groin. Two consecutive cardiology exams, performed at nine months from one another, showed a decrease of almost 21% in the ejection fraction of the left ventricle. An angiography was conducted with the hope of achieving effective percutaneous embolization. Unfortunately, that was not the case. An open repair was scheduled, as the option for a stent-graft deployment was overruled as being too risky, potentially closing several branches of the profunda femoris artery and not fully completing the orifice due to a complicated anatomical positioning. Under local anesthesia, an open ligation was performed in very hostile anatomical conditions. The patient had an uncomplicated evolution and was discharged on the third day, symptom-free. CONCLUSIONS: Iatrogenic arteriovenous fistulas are rare. Clinical presentation diagnoses the case efficiently, vascular imaging being essential for surgical preparation. Though open repair is not the gold standard, there are cases not suitable for the endovascular approach. These patients are eligible for a surgical solution, not without technical challenges.

Endovascular treatment of an aneurysm associated with fenestration of the supraclinoid internal carotid artery: Case report and review of the literature.

Background: Fenestrations or divisions of the vascular lumen into separate channels appear to be common anatomical variations in patients with intracranial aneurysms. The most frequent sites of occurrence are the anterior communicating artery (ACom), followed by vertebrobasilar and middle cerebral artery (MCA) locations. Case presentation: A 61-year-old female was brought to the emergency department after experiencing severe headache with abrupt onset, nausea, and vomiting. Clinical examination on arrival showed a drowsy patient (GCS 14), with neck stiffness, but no cranial nerve palsies or other neurological deficits (Hunt-Hess 2). Non-contrast head CT and CT angiography revealed subarachnoid and intraventricular hemorrhage (modified Fisher 4) and two saccular aneurysms, one located on the right supraclinoid ICA with peripheral calcifications, measuring 20 × 12 mm, the second on the left MCA bifurcation, 6 × 4 mm. 3D rotational angiography revealed a right ICA fenestration located between the ophthalmic (OA) and posterior communicating artery (PCom). The proximal part of the fenestration harbored a large saccular aneurysm projecting superiorly with the neck engulfing the origin of the fenestration; due to the favorable neck and geometry of the aneurysm, endovascular coil occlusion was chosen as a treatment option without balloon or stent assistance. The decision was taken to clip the MCA aneurysm. Conclusion: Supraclinoid ICA fenestrations are rare anatomical variations. Endovascular treatment of supraclinoid ICA fenestration-related aneurysms is feasible and safe, with the notable concern of perforators originating from the limbs.

Neutrophil­to­lymphocyte, platelet­to­lymphocyte and lymphocyte­to­monocyte ratios are associated with amputation rates in patients with peripheral arterial disease and diabetes mellitus who underwent revascularization: A Romanian regional center study.

Inflammation plays an important role in peripheral artery disease (PAD), contributing to the onset and progression of atherosclerosis, as well as to the rupture of atherosclerotic plaques. Studies have revealed that due to their inflammatory nature, leucocytes play an important role in the development of atherosclerosis. A retrospective study was conducted involving 203 patients with PAD admitted to Targu Mures Emergency County Hospital for revascularization surgery between January 2017 and June 2019 (of which 47 were treated by endovascular intervention, and 156 underwent classical surgical intervention). Among all patients included in the study, 47 patients required amputation following the revascularization intervention. The results indicated that though the mean patient age in the non-amputation group was higher than that in the amputation group, that the difference was not significant. With regard to sex distribution, 72% of the patients from the amputation group were male, while from the non-amputation group, 74% were male. The neutrophil-to-lymphocyte ratio (NLR) cut-off value for the prediction of amputation in PAD was 3.485 (sensitivity, 60.42%; specificity 72.44%), whereas the platelet-to-lymphocyte ratio (PLR) value was 152, (sensitivity, 54.17%; specificity, 71.79%), and was 2.55 for the lymphocyte-to-monocyte ration (LMR; sensitivity, 56.25%; specificity, 66.88%). The study concluded that in patients with PAD, the NLR and PLR were increased, while the LMR was decreased, which was also associated with a higher rate of amputation after revascularization, despite the lack of correlation between these factors, Fontaine classification and the number of damaged vessels. Therefore, pre-operative alterations in NLR, PLR and LMR may predict the need for amputation in patients with PAD, or those who underwent a revascularization intervention.

Road to disorder in smectic elastomers.

We present a high-resolution x-ray study of the effects of disorder induced by random cross-linking side-chain smectic elastomers. The influence of variation of the concentration and stiffness of the cross-link units on the disruption of the one-dimensional translational order is reported in detail. Precise analysis of the line shape of the quasi-Bragg peaks associated with the smectic layering indicates a transition from algebraic decaying ordering to disorder. The smectic line shapes can be described by the Caillé correlation function convoluted with a finite-size factor represented by a stretched Gaussian (compressed exponential). The transition to disorder is signaled by a change in the exponent of the stretched Gaussian from 1 (simple Gaussian describing finite-size domains) via 0.5 (Lorentzian describing exponentially decaying short-range correlations) to <0.5 (stretched exponential correlations). For a flexible cross linker the changeover occurs for concentration between 0.15 and 0.20, for a stiff cross linker below about 0.10. Broadening of the higher harmonics of the x-ray peak indicates strong nonuniform strain within finite-size domains and local deformations induced by randomly distributed dislocations.

MRI of perfluorocarbon emulsion kinetics in rodent mammary tumours.

Perfluorocarbon (PFC) emulsions can be imaged directly by fluorine-19 MRI. We developed an optimized protocol for preparing PFC droplets of uniform size, evaluated use of the resulting droplets as blood pool contrast agents, studied their uptake by tumours and determined the spatial resolution with which they can be imaged at 4.7 T. Perfluorocarbon droplets of three different average sizes (324, 293 and 225 nm) were prepared using a microemulsifier. Images of PFC droplets with good signal-to-noise ratio were acquired with 625 microm in-plane resolution, 3 mm slice thickness and acquisition time of approximately 4.5 min per image. Kinetics of washout were determined using a simple mathematical model. The maximum uptake of the PFC droplets was three times greater at the tumour rim than in muscle, but the washout rate was two to three times slower in the tumour. The results are consistent with leakage of the droplets into the tumour extravascular space due to the hyper-permeability of tumour capillaries. PFC droplets may allow practical and quantitative measurements of blood volume and capillary permeability in tumours with reasonable spatial resolution.

Dynamic heterogeneity in hydrogen-bonded polymers.

We report on neutron spin echo experiments on hydrogen-bonded polymers and compare the experimentally found dynamical structure factor with theoretical predictions. Surprisingly, we find that in the melt phase the expected scaling of the Rouse dynamics is not satisfied. We propose an explanation based upon the large spatial volume occupied by the connecting groups. When the effects of these bulky groups on the local friction are taken into account, the usual scaling behavior is restored.

Urea modulation of beta-amyloid fibril growth: experimental studies and kinetic models.

Aggregation of beta-amyloid (Abeta) into fibrillar deposits is widely believed to initiate a cascade of adverse biological responses associated with Alzheimer's disease. Although it was once assumed that the mature fibril was the toxic form of Abeta, recent evidence supports the hypothesis that Abeta oligomers, intermediates in the fibrillogenic pathway, are the dominant toxic species. In this work we used urea to reduce the driving force for Abeta aggregation, in an effort to isolate stable intermediate species. The effect of urea on secondary structure, size distribution, aggregation kinetics, and aggregate morphology was examined. With increasing urea concentration, beta-sheet content and the fraction of aggregated peptide decreased, the average size of aggregates was reduced, and the morphology of aggregates changed from linear to a globular/linear mixture and then to globular. The data were analyzed using a previously published model of Abeta aggregation kinetics. The model and data were consistent with the hypothesis that the globular aggregates were intermediates in the amyloidogenesis pathway rather than alternatively aggregated species. Increasing the urea concentration from 0.4 M to 2 M decreased the rate of filament initiation the most; between 2 M and 4 M urea the largest change was in partitioning between the nonamyloid and amyloid pathways, and between 4 M and 6 M urea, the most significant change was a reduction in the rate of filament elongation.

Giant dermatofibrosarcoma protuberans - rare form of mesenchymal tissue neoplasm: case presentation.

UNLABELLED: Dermatofibrosarcoma protuberans (DFSP), a rare type of mesenchymal neoplasm, is defined by the WHO as a superficial sarcoma with low-grade malignancy that develops in the cutaneous and subcutaneous tissues. The purpose of this paper is to present a case of a giant DFSP, with post-traumatic onset in childhood and a very long evolution. CLINICAL DATA: 51-year-old Caucasian patient presents for 41 years a presternal neoplastic lesion, with onset at 10-year-old, few months after a strong trauma. The patient addressed for a clinic examination, secondary to a spontaneous hemorrhage of the lesion. The local examination reveals the presence of a red-purple polynodular neoplastic lesion of 180×110×30 mm, of firm consistency, adherent to the subcutaneous tissue, painless, with lateral extension at 8 o'clock as an erythematous infiltrated atrophic plaque appearance. One of these nodular masses presents surface ulceration and areas of necrosis. The CT scan did not detect any infiltration into the pectoral muscle or loco-regional metastasis. Under general anesthesia a wide surgical excision with free macroscopic margins of 3 cm was performed. Histopathological diagnosis was DFSP, with evidence of tumoral spindle cells disposed in storiform pattern, embedding small adipocyte panicles, creating a lace-like or honeycomb appearance. Immunohistochemically, the tumor cells express an intense and diffuse CD34 and they are negative for S-100 and SMA. The Ki-67 is focal positive in almost 2-4%. Clinical and paraclinical monitoring at 18 months follow-up does not detect any local recurrences or metastases, and an excellent quality of life.

Influence of fines on the surface energy heterogeneity of lactose for pulmonary drug delivery.

The effects of the blending of lactose fines to the overall adhesion property of coarse alpha-lactose monohydrate carrier particles were investigated. Five samples, three of them commercial samples from DOMO (Lactohale) LH100, LH210, and LH250) whilst the other two are blends of LH210 and LH250, were studied. Characterisation included particle sizing, SEM, PXRD and IGC. Dispersive surface energy gamma(SV)(d) was determined using a finite concentration IGC method to obtain a distribution profile. The gamma(SV)(d) distribution of lactose crystals was found to vary from 40 to 48mJ/m(2). The unmilled coarse crystalline lactose sample (LH100) gamma(SV)(d) was lowest and showed less heterogeneity than the milled sample (LH250). Fines (LH210) were found to have the highest gamma(SV)(d) value. The samples with loaded LH210 were found to have a higher energy than LH100. The amount of LH210 in Blend 1 was not able to decrease surface energy heterogeneity, whereas sample Blend 2 showed adequate loading of fines to obtain a relatively homogeneous surface. Addition of fines resulted in an increase in gamma(SV)(d), suggesting that coarse lactose surfaces were replaced by surfaces of the fines. Increasing the loading of fines may result in a more homogeneous surface energy of lactose particles.

Interaction of antimicrobial peptide protegrin with biomembranes.

The antimicrobial peptide protegrin-1 (PG-1) interacts with membranes in a manner that strongly depends on membrane lipid composition. In this research we use an approach representing the outer layers of bacterial and red blood cell membranes with lipid monolayers and using a combination of insertion assay, epifluorescence microscopy, and surface x-ray scattering to gain a better understanding of antimicrobial peptide's mechanism of action. We find that PG-1 inserts readily into anionic dipalmitoyl-phosphatidylglycerol, palmitoyl-oleoyl-phosphatidylglycerol, and lipid A films, but significantly less so into zwitterionic dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylcholine, and dipalmitoyl-phosphatidylethanolamine monolayers under similar experimental conditions. Epifluorescence microscopy shows that the insertion of PG-1 into the lipid layer results in the disordering of lipid packing; this disordering effect is corroborated by grazing incidence x-ray diffraction data. X-ray reflectivity measurements further point to the location of the peptide in the lipid matrix. In a pathologically relevant example we show that PG-1 completely destabilizes monolayer composed of lipid A, the major component in the outer membrane of Gram-negative bacteria, which is likely to be the mechanism by which PG-1 disrupts the outer membrane, thus allowing it to reach the target inner membrane.