Effect of Aneurysm and Patient Characteristics on Intracranial Aneurysm Wall Thickness.

Background: The circle of Willis is a network of arteries allowing blood supply to the brain. Bulging of these arteries leads to formation of intracranial aneurysm (IA). Subarachnoid hemorrhage (SAH) due to IA rupture is among the leading causes of disability in the western world. The formation and rupture of IAs is a complex pathological process not completely understood. In the present study, we have precisely measured aneurysmal wall thickness and its uniformity on histological sections and investigated for associations between IA wall thickness/uniformity and commonly admitted risk factors for IA rupture. Methods: Fifty-five aneurysm domes were obtained at the Geneva University Hospitals during microsurgery after clipping of the IA neck. Samples were embedded in paraffin, sectioned and stained with hematoxylin-eosin to measure IA wall thickness. The mean, minimum, and maximum wall thickness as well as thickness uniformity was measured for each IA. Clinical data related to IA characteristics (ruptured or unruptured, vascular location, maximum dome diameter, neck size, bottleneck factor, aspect and morphology), and patient characteristics [age, smoking, hypertension, sex, ethnicity, previous SAH, positive family history for IA/SAH, presence of multiple IAs and diagnosis of polycystic kidney disease (PKD)] were collected. Results: We found positive correlations between maximum dome diameter or neck size and IA wall thickness and thickness uniformity. PKD patients had thinner IA walls. No associations were found between smoking, hypertension, sex, IA multiplicity, rupture status or vascular location, and IA wall thickness. No correlation was found between patient age and IA wall thickness. The group of IAs with non-uniform wall thickness contained more ruptured IAs, women and patients harboring multiple IAs. Finally, PHASES and ELAPSS scores were positively correlated with higher IA wall heterogeneity. Conclusion: Among our patient and aneurysm characteristics of interest, maximum dome diameter, neck size and PKD were the three factors having the most significant impact on IA wall thickness and thickness uniformity. Moreover, wall thickness heterogeneity was more observed in ruptured IAs, in women and in patients with multiple IAs. Advanced medical imaging allowing in vivo measurement of IA wall thickness would certainly improve personalized management of the disease and patient care.

Correlating Clinical Risk Factors and Histological Features in Ruptured and Unruptured Human Intracranial Aneurysms: The Swiss AneuX Study.

Pathogenesis of intracranial aneurysm is complex and the precise biomechanical processes leading to their rupture are uncertain. The goal of our study was to characterize the aneurysmal wall histologically and to correlate histological characteristics with clinical and radiological factors used to estimate the risk of rupture. A new biobank of aneurysm domes resected at the Geneva University Hospitals (Switzerland) was used. Histological analysis revealed that unruptured aneurysms have a higher smooth muscle cell (SMC) content and a lower macrophage content than ruptured domes. These differences were associated with more collagen in unruptured samples, whereas the elastin content was not affected. Collagen content and type distribution were different between thick and thin walls of unruptured aneurysms. Classification of aneurysm domes based on histological characteristics showed that unruptured samples present organized wall rich in endothelial and SMCs compared with ruptured samples. Finally, aneurysm wall composition was altered in unruptured domes of patients presenting specific clinical factors used to predict rupture such as large dome diameter, dome irregularities, and smoking. Our study shows that the wall of aneurysm suspected to be at risk for rupture undergoes structural alterations relatively well associated with clinical and radiological factors currently used to predict this risk.

Fate of the open-shell singlet ground state in the experimentally accessible acenes: A quantum Monte Carlo study.

By means of the Jastrow correlated antisymmetrized geminal power (JAGP) wave function and quantum Monte Carlo (QMC) methods, we study the ground state properties of the oligoacene series, up to the nonacene. The JAGP is the accurate variational realization of the resonating-valence-bond (RVB) ansatz proposed by Pauling and Wheland to describe aromatic compounds. We show that the long-ranged RVB correlations built in the acenes' ground state are detrimental for the occurrence of open-shell diradical or polyradical instabilities, previously found by lower-level theories. We substantiate our outcome by a direct comparison with another wave function, tailored to be an open-shell singlet (OSS) for long-enough acenes. By comparing on the same footing the RVB and OSS wave functions, both optimized at a variational QMC level and further projected by the lattice regularized diffusion Monte Carlo method, we prove that the RVB wave function has always a lower variational energy and better nodes than the OSS, for all molecular species considered in this work. The entangled multi-reference RVB state acts against the electron edge localization implied by the OSS wave function and weakens the diradical tendency for higher oligoacenes. These properties are reflected by several descriptors, including wave function parameters, bond length alternation, aromatic indices, and spin-spin correlation functions. In this context, we propose a new aromatic index estimator suitable for geminal wave functions. For the largest acenes taken into account, the long-range decay of the charge-charge correlation functions is compatible with a quasi-metallic behavior.

Vertical and adiabatic excitations in anthracene from quantum Monte Carlo: Constrained energy minimization for structural and electronic excited-state properties in the JAGP ansatz.

We study the ionization energy, electron affinity, and the π → π(∗) ((1)La) excitation energy of the anthracene molecule, by means of variational quantum Monte Carlo (QMC) methods based on a Jastrow correlated antisymmetrized geminal power (JAGP) wave function, developed on molecular orbitals (MOs). The MO-based JAGP ansatz allows one to rigorously treat electron transitions, such as the HOMO → LUMO one, which underlies the (1)La excited state. We present a QMC optimization scheme able to preserve the rank of the antisymmetrized geminal power matrix, thanks to a constrained minimization with projectors built upon symmetry selected MOs. We show that this approach leads to stable energy minimization and geometry relaxation of both ground and excited states, performed consistently within the correlated QMC framework. Geometry optimization of excited states is needed to make a reliable and direct comparison with experimental adiabatic excitation energies. This is particularly important in π-conjugated and polycyclic aromatic hydrocarbons, where there is a strong interplay between low-lying energy excitations and structural modifications, playing a functional role in many photochemical processes. Anthracene is an ideal benchmark to test these effects. Its geometry relaxation energies upon electron excitation are of up to 0.3 eV in the neutral (1)La excited state, while they are of the order of 0.1 eV in electron addition and removal processes. Significant modifications of the ground state bond length alternation are revealed in the QMC excited state geometry optimizations. Our QMC study yields benchmark results for both geometries and energies, with values below chemical accuracy if compared to experiments, once zero point energy effects are taken into account.

The natural progression of adult elbow osteonecrosis related to corticosteroid treatment.

BACKGROUND: In patients with corticosteroid treatment, the elbow is a rare site of osteonecrosis; there is little information about the rate and risk factors of disease progression in symptomatic and asymptomatic elbows. QUESTION/PURPOSES: We determined the delay between the beginning of corticosteroid treatment and different stages of osteonecrosis and which stage and dose of steroids influenced disease progression. METHODS: Osteonecrosis related to corticosteroids was diagnosed by MRI in 50 elbows of 35 adult patients. Thirty elbows were asymptomatic at initial evaluation (19 with Stage I, 11 with Stage II osteonecrosis). Among the 20 elbows symptomatic at initial evaluation, 13 had radiographic evidence of osteonecrosis without collapse (Stage II) and seven had lesions evident only on MRI (Stage I). RESULTS: At latest followup (average, 17 years; range, 10-25 years), of the 30 previously asymptomatic elbows, pain developed in 24 and collapse occurred in 14; of the 20 previously symptomatic elbows, 15 showed collapse (seven initially with Stage I, eight with Stage II osteonecrosis). The average time between diagnosis and collapse was 8 and 5 years, respectively, for symptomatic elbows with Stages I and II osteonecrosis. Stage at initial visit, development of pain, and continuation of peak doses of corticosteroids were risk factors for disease progression in asymptomatic elbows. In symptomatic elbows, the extent in contact with the articular surface and lesion location were the main risk factors for disease progression. CONCLUSIONS: Untreated asymptomatic and symptomatic elbow osteonecrosis related to corticosteroids has a moderate likelihood of elbow collapse, with decrease in ROM, but none of the patients in this case series followed for 10 to 20 years had elbow arthroplasty. LEVEL OF EVIDENCE: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Alumina heads minimize wear and femoral osteolysis progression after isolated simple acetabular revision.

BACKGROUND: Patients with THA requiring cup revision for acetabular osteolysis may have a stable stem component without loosening. However, it is unclear whether isolated cup revision halts femoral osteolysis progression. QUESTION/PURPOSES: We asked (1) whether and to what degree osteolysis progresses after isolated acetabular revision with a change of the femoral head and (2) whether an alumina or metal bearing better reduces osteolysis progression and wear with a polyethylene (PE) cup. METHODS: We retrospectively evaluated 150 patients who underwent 165 acetabular revisions but no treatment for proximal femoral osteolysis in hips with stable femoral components. Mean age at revision was 63 years (range, 48-74 years). All hips received a new PE cup; 83 hips received new alumina heads and 82 new metal heads. Radiographs (mean followup, 15 years; range, 10-25 years) were assessed to measure osteolysis, loosening, and PE wear. Revisions of the femoral stem were recorded. RESULTS: An isolated cup revision with a change of the femoral head halted femoral osteolysis progression for 10 years in 133 hips (81%), with a greater percentage without progression in hips with alumina heads (99% versus 62% with metal head). Alumina heads were better than metal heads at reducing the area of osteolysis progression (47 versus 250 mm(2)) and wear (0.07 versus 0.14 mm/year) and increasing the survival probability before femoral revision (98% versus 85% at 15 years' followup). CONCLUSIONS: An isolated cup revision with a new alumina femoral head (in hips that have a stable stem component without loosening) usually halts femoral osteolysis progression (no change or osseous restoration) over 10 years if the osteolysis is less than 1000 mm(2). LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.