4D-DSA for Assessment of the Angioarchitecture and Grading of Cranial Dural AVF.

BACKGROUND AND PURPOSE: Time-resolved 3D rotational angiography (4D-DSA) has been used to demonstrate details of the angioarchitecture of AVM, whereas it has rarely been used to describe features of dural AVF. In this exploratory study, we analyzed dural AVFs with a novel 4D software prototype, developed and provided by Siemens, to determine whether identification of the location of the fistulous point, grading, and treatment planning were feasible. MATERIALS AND METHODS: 4D-DSA volumes were calculated from existing 3D rotational angiography data sets of patients with dural AVFs. The 4D-DSA volumes were displayed in a virtual DSA mode and MPR or MIP in 3 orthogonal planes and compared with 2D-DSA by 2 experienced neuroradiologists. Fusions with unenhanced CT or MR images were used to improve visualization of adjacent anatomic structures. RESULTS: Comparison with 2D-DSA showed that evaluation of the fistulous point and grading according to the classification of Borden, Cognard, or Barrow was feasible in 26 of 27 cases. In 8 of 27 cases, 4D-DSA was considered advantageous for determining the fistulous point and the course of the draining vein in the dural AVF with cortical venous drainage, especially in the frontoethmoidal and frontoparietal regions. In 6 cases, the display of angioarchitecture was considered inferior to that of 2D-DSA due to motion artifacts, suboptimal selection of the injected vessel, and lack of temporal resolution. CONCLUSIONS: Detailed analysis of dural AVFs according to the standardized display of 4D-DSA volumes was feasible and helpful in understanding the angioarchitecture in selected cases. Further improvement and validation of the 4D software should solidify the complementary role of 4D-DSA to conventional 2D-DSA series.

Standard values of the upper body posture in healthy adults with special regard to age, sex and BMI.

In order to classify and analyze the parameters of upper body posture in clinical or physiotherapeutic settings, a baseline in the form of standard values with special regard to age, sex and BMI is required. Thus, subjectively healthy men and women aged 21-60 years were measured in this project. The postural parameters of 800 symptom-free male (n = 397) and female (n = 407) volunteers aged 21-60 years (Ø♀: 39.7 ± 11.6, Ø â™‚: 40.7 ± 11.5 y) were studied. The mean height of the men was 1.8 ± 0.07 m, with a mean body weight of 84.8 ± 13.1 kg and an average BMI of 26.0 ± 3.534 kg/m2. In contrast, the mean height of the women was 1.67 ± 0.06 m, with a mean body weight of 66.5 ± 12.7 kg and an average BMI of 23.9 ± 4.6 kg/m2. By means of video rasterstereography, a 3-dimensional scan of the upper back surface was measured when in a habitual standing position. The means or medians, confidence intervals, tolerance ranges, the minimum, 2.5, 25, 50, 75, 97.5 percentiles and the maximum, plus the kurtosis and skewness of the distribution, were calculated for all parameters. Additionally, ANOVA and a factor analyses (sex, BMI, age) were conducted. In both sexes across all age groups, balanced, symmetrical upper body statics were evident. Most strikingly, the females showed greater thoracic kyphosis and lumbar lordosis angles (kyphosis: Ø â™€ 56°, Ø♂ 51°; lordosis: Ø â™€ 49°, Ø♂ 32°) and lumbar bending angles (Ø â™€ 14°, Ø♂ 11°) than the males. The distance between the scapulae was more pronounced in men. These parameters also show an increase with age and BMI, respectively. Pelvic parameters were independent of age and sex. The upper body postures of women and men between the ages of 21 and 60 years were found to be almost symmetrical and axis-conforming with a positive correlation for BMI or age. Consequently, the present body posture parameters allow for comparisons with other studies, as well as for the evaluation of clinical (interim) diagnostics and applications.

4D Flat Panel Conebeam CTA for Analysis of the Angioarchitecture of Cerebral AVMs with a Novel Software Prototype.

BACKGROUND AND PURPOSE: Time-resolved 3DRA (4D-DSA) and flat panel conebeam CTA are new methods for visualizing the microangioarchitecture of cerebral AVMs. We applied a 4D software prototype to a series of cases of AVMs to assess the utility of this method in relation to treatment planning. MATERIALS AND METHODS: In 33 patients with AVMs, 4D volumes and flat panel conebeam CTA images were recalculated from existing 3D rotational angiography data. The multiplanar reconstructions were used to determine intranidal arteriovenous branching patterns, categorize them according to common classifications of AVM angioarchitecture, and compare the results with those from 2D-DSA. RESULTS: 4D flat panel conebeam CTA showed angioarchitectural features equal to or better than those of 2D-DSA in 30 of 33 cases. In particular, the reconstructions helped in understanding the intranidal microvasculature. Fistulous direct arteriovenous connections with a low degree of arterial branching (n = 22) could be distinguished from plexiform arterial networks before the transition to draining veins (n = 11). We identified AVMs with a single draining vein (n = 20) or multiple draining veins (n = 10). Arteriovenous shunts in the lateral wall of the draining veins (n = 22) could be distinguished from cases with increased venous branching and shunts between corresponding intranidal arteries and veins (n = 11). Limitations were the time-consuming postprocessing and the difficulties in correctly tracing intranidal vessels in larger and complex AVMs. CONCLUSIONS: 4D flat panel conebeam CTA reconstructions allow detailed analysis of the nidal angioarchitecture of AVMs. However, further improvements in temporal resolution and automated reconstruction techniques are needed to use the method generally in clinical practice.

The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria (PNH): experience of the Austrian PNH network.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978-2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55% and was higher in patients with classical PNH (81%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5-32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.

4D Flat Panel Conebeam CTA for In Vivo Imaging of the Microvasculature of the Human Cortex with a Novel Software Prototype.

It was the aim of our pilot study to investigate whether time-resolved flat panel conebeam CTA is able to demonstrate small cortical vessels in vivo. In 8 patients with small AVMs, time-resolved coronal MPRs of the vasculature of the frontal cortex were recalculated from 3D rotational angiography datasets with the use of a novel software prototype. 4D flat panel conebeam CTA demonstrated the course of the cortical arteries with small perpendicular side branches to the underlying cortex. Pial arterial and venous networks could also be identified, corresponding to findings in injection specimens. Reasonable image quality was achieved in 6 of 8 cases. In this small study, in vivo display of the cortical microvasculature with 4D flat panel conebeam CTA was feasible and superior to other angiographic imaging modalities.

[A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic]. / Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie ­ eine Situationsanalyse.

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

Efficacy of Mechanical Thrombectomy Using Stent Retriever and Balloon-Guiding Catheter.

PURPOSE: Intra-arterial therapy of acute ischemic stroke has developed rapidly in recent years. Due to proven efficacy in randomized trials, stent retrievers were replacing first-generation thrombectomy devices and have been defined as method of choice. However, aspiration catheters or a combination of several techniques have shown promising rates of successful recanalizations. To create a basis for comparison of the new approaches according to real-world data, we determined the first pass recanalization rate of an evidence-based standard technique with the use of a stent retriever in combination with a balloon-guiding catheter. The assessment was based on the number of required passages and reperfusion rate, but not on clinical results. METHODS: Patients from our institution with anterior circulation occlusions and mechanical thrombectomy by using stent retrievers in combination with balloon-guiding catheters were analyzed retrospectively. Reperfusion was graded with the "thrombolysis in cerebral infarction" (TICI) classification on post-interventional angiograms. Additionally, the number of passes and the duration of the recanalization procedure were recorded. RESULTS: Between 2014 and July 2017, 201 patients met the inclusion criteria. Successful recanalization, defined as a TICI scale 2b/3, was 91% (TICI 2b was achieved in 44% and TICI 3 in 47%) after the procedure. After the first passage, successful recanalization was achieved in 65% of the patients. Mean number of passes was 1.4 (1-5 passes) for all patients. Median duration of the procedure was 49 min (0:11-2:35 h). CONCLUSIONS: Even a standard thrombectomy technique with the use of a stent retriever together with a balloon-guiding catheter provides reasonable recanalization rates with only one passage. The results can be taken as benchmark for alternative and more complex techniques.

Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic.

Quantitative predictions of biomembrane/water partition coefficients are important, as they are a key property in pharmaceutical applications and toxicological studies. Molecular dynamics (MD) simulations are used to calculate free energy profiles for different solutes in lipid bilayers. How to calculate partition coefficients from these profiles is discussed in detail and different definitions of partition coefficients are compared. Importantly, it is shown that the calculated coefficients are in quantitative agreement with experimental results. Furthermore, we compare free energy profiles from MD simulations to profiles obtained by the recent method COSMOmic, which is an extension of the conductor-like screening model for realistic solvation to micelles and biomembranes. The free energy profiles from these molecular methods are in good agreement. Additionally, solute orientations calculated with MD and COSMOmic are compared and again a good agreement is found. Four different solutes are investigated in detail: 4-ethylphenol, propanol, 5-phenylvaleric acid, and dibenz[a,h]anthracene, whereby the latter belongs to the class of polycyclic aromatic hydrocarbons. The convergence of the free energy profiles from biased MD simulations is discussed and the results are shown to be comparable to equilibrium MD simulations. For 5-phenylvaleric acid the influence of the carboxyl group dihedral angle on free energy profiles is analyzed with MD simulations.

Multiscale modelling in computational heterogeneous catalysis.

The goal of multiscale modelling of heterogeneous catalytic reactors is the prediction of all steps, starting from the reaction mechanism at the active centre, the rates of reaction, adsorption and diffusion processes inside the porous system of the catalyst support, based on first principles, quantum chemistry, force field simulations and macroscopic differential equations. The progress in these fields of research will be presented, including linking models between the various levels of description. Alkylation of benzene will be used as an example to demonstrate the various approaches from the active centre to the reactor.

First-principles investigation of the adsorption of the 2,5-pyridine di-carboxylic acid onto the Cu(011) surface.

First-principles calculations within the density functional theory (DFT) framework have been performed in order to investigate various conformations of the 2,5-pyridine di-carboxylic acid (PDCA) molecule adsorbed onto the Cu(011) surface. By means of DFT calculations the adsorption geometry, the bond formation and the electronic properties of PDCA molecule conformations on the Cu(011) surface have been studied. The most important structural property is the orientation of the COOH H atom which can point either toward the aromatic ring or toward the vacuum. This H atom position determines the possible reactions in which the adsorbed molecule can get involved and also has a significant impact on the value of the Cu-molecule system work function. Thus, we find that simply by changing the H atom orientation (from up to down) the Cu-molecule system work function can be varied with more than 2.5 eV. This is a significant result as a lot of effort is put nowadays in finding efficient ways for the in situ variation of the systems work function. Scanning tunneling microscopy (STM) images, reflexion absorption infrared vibrational spectra (RAIRS) as well as various thermodynamic properties (adsorption entropies, enthalpies) have also been investigated in order to get a better insight into the system studied and to provide support to possible experimental studies (STM or RAIRS experiments).

Diffusion of chain molecules and mixtures in carbon nanotubes: the effect of host lattice flexibility and theory of diffusion in the Knudsen regime.

A novel algorithm for modeling the influence of the host lattice flexibility in molecular dynamics simulations is extended to chain-like molecules and mixtures. This technique, based on a Lowe-Andersen thermostat, maintains the advantages of both simplicity and efficiency. The same diffusivities and other properties of the flexible framework system are reproduced. Advantageously, the computationally demanding flexible host lattice simulations can be avoided. Using this methodology we study the influence of flexibility on diffusion of n-alkanes inside single-walled carbon nanotubes. Furthermore, results are shown for diffusion of two mixtures (methane-helium and ethane-butane). Using these results we investigate the accuracy of theories describing diffusion in the Knudsen regime. For the dynamics in carbon nanotubes the Knudsen diffusivities are much too low. The Smoluchowski model gives better results. Interestingly, the extended Smoluchowski model can reproduce our simulation results obtained with a rigid host lattice. We modify this model to also treat collisions with a flexible interface correctly. As the tangential momentum accommodation coefficient is needed for the theoretical models, we introduce a simple concept to calculate it.

Combining reactive and configurational-bias Monte Carlo: confinement influence on the propene metathesis reaction system in various zeolites.

In order to efficiently calculate chemical equilibria of large molecules in a confined environment the reactive Monte Carlo technique is combined with the configurational-bias Monte Carlo approach. To prove that detailed balance is fulfilled the acceptance rule for this combination of particular Monte Carlo techniques is derived in detail. Notably, by using this derivation all other acceptance rules of any Monte Carlo trial moves usually carried out in combination with the configurational-bias Monte Carlo approach can be deduced from it. As an application of the combination of reactive and configurational-bias Monte Carlo the influence of different zeolitic confinements (MFI, TON, LTL, and FER) on the reaction equilibrium and the selectivity of the propene metathesis reaction system was investigated. Compared to the bulk phase the conversion is increased significantly. The authors study this reaction system in the temperature range between 300 and 600 K, and the pressure range from 1 to 7 bars. In contrast to the bulk phase, pressure and temperature have a strong influence on the composition of the reaction mixture in confinement. At low pressures and temperatures both conversion and selectivity are highest. Furthermore, the equilibrium composition is strongly dependent on the type of zeolite. This demonstrates the important role of the host structure in catalytic systems.

Temperature and size effects on diffusion in carbon nanotubes.

We study the self-diffusion of simple gases inside single-walled carbon nanotubes at the zero-loading limit by molecular dynamics simulations. The host-framework flexibility influence is taken into account. In particular, we study the influences of nanotube size and temperature. For the carbon-nanotube radius-dependent self-diffusivities, a maximum is observed, which resembles the so-called levitation effect. This occurs for pores having a radius comparable to the position of the interaction-energy minimum. Surprisingly, the temperature influence is not uniform throughout different pore sizes. Diffusivities are expected to increase with temperature. This effect is observed for carbon nanotubes distinctly larger than the guest molecules. Remarkably, for smaller pores, the self-diffusivities decrease with increasing temperature or exhibit a maximum in the temperature dependence. This effect is caused by competing influences of collision frequency and temperature.

A novel algorithm to model the influence of host lattice flexibility in molecular dynamics simulations: loading dependence of self-diffusion in carbon nanotubes.

We describe a novel algorithm that includes the effect of host lattice flexibility into molecular dynamics simulations that use rigid lattices. It uses a Lowe-Andersen thermostat for interface-fluid collisions to take the most important aspects of flexibility into account. The same diffusivities and other properties of the flexible framework system are reproduced at a small fraction of the computational cost of an explicit simulation. We study the influence of flexibility on the self-diffusion of simple gases inside single walled carbon nanotubes. Results are shown for different guest molecules (methane, helium, and sulfur hexafluoride), temperatures, and types of carbon nanotubes. We show, surprisingly, that at low loadings flexibility is always relevant. Notably, it has a crucial influence on the diffusive dynamics of the guest molecules.

Are sweat glands an alternate penetration pathway? Understanding the morphological complexity of the axillary sweat gland apparatus.

To build an effective barrier against the penetration of extrinsic agents is one of the skin's main functions. The barrier properties of the stratum corneum and the epidermis have been subject to extensive studies in the past while the role of skin appendages as possible pathways of penetration are only rarely described. In order to study the possible penetration barriers in these complex appendages, a careful investigation of their morphology and ultrastructure has to be done. Studying the morphology of axillary skin appendages requires clear-cut criteria for the differentiation between eccrine, apocrine and apoeccrine glands. Therefore we studied the distribution of proteins described to be specific for either eccrine or apocrine glands (CD15, CD44, S-100 and milk fat globulin) on axillary skin samples from healthy young adults by immunofluorescence. Additionally, we examined the distribution of cytoskeletal proteins such as cytokeratins (1/10/11, 14, 18) and F-actin. For a more detailed understanding of the possible versatile barrier elements of the axillary sweat glands, we studied the distribution of tight-junction-associated proteins (occludin, claudin 1, claudin 4). The coils and the dermal duct may provide an active barrier built of tight junctions as occludin and claudin 4 are co-localized. However, the intra-epidermal duct did not show any co-localization of the investigated proteins. By combining morphological features as revealed by F-actin staining and the distribution of the above-mentioned proteins, immunocytochemical typing of eccrine and apocrine glands becomes possible. With this tool, we could also confirm the existence of apoeccrine glands and locate them in their 'natural environment'.

Understanding the loading dependence of self-diffusion in carbon nanotubes.

The influence of flexible walls on the self-diffusion of CH4 in an isolated single walled carbon nanotube, as an example, is studied by molecular dynamics simulations. By simulating the carbon nanotube as a flexible framework we demonstrate that the flexibility has a crucial influence on self-diffusion at low loadings. We show how this influence can be incorporated in a simulation of a rigid nanotube by using a Lowe-Andersen thermostat which works on interface-fluid collisions. The reproduction of the results of a flexible carbon nanotube by a rigid nanotube simulation is excellent.

Thrombocytosis in gynecologic malignancies.

Recent studies have addressed the prevalence and prognostic impact of thrombocytosis in various gynecologic and non-gynecologic malignancies. Thrombocytosis appears to be of prognostic value in certain patients with gynecologic malignancies. In this survey we review the published data and attempt to analyze the prognostic implications of thrombocytosis in patients with gynecologic malignancies.

Early and late gastrointestinal complications after myeloablative and nonmyeloablative allogeneic stem cell transplantation.

Upper and lower gastrointestinal symptoms are major and serious complications after stem cell transplantation. Their main causes are gastrointestinal graft-versus-host disease (GVHD), infections, toxicity, or preexisting gastrointestinal diseases. The clinical presentation of each disease is nonspecific. The diagnostic procedure for this study included physical exam, stool cultures, endoscopy with biopsies, and abdominal computed tomography (CT). The study was designed prospectively with consecutive patients and performed at our institution in a clinical stem cell transplantation setting. Between January 1996 and September 2001, we analyzed 42 consecutive patients who had been admitted at our institution for gastrointestinal complaints after allogeneic stem cell transplantation for hematologic diseases. Diagnostic procedures revealed in decreasing order: GVHD (62%), gastritis/esophagitis (19%), cytomegalovirus (CMV) enteritis (11%), bacterial enteritis (6%), and toxic mucosal damage (2%). CT showed unspecific findings. Gastrointestinal GVHD and infectious colitis accounted for the majority of gastrointestinal complications after allogeneic stem cell transplantation in our patient population. The diagnosis was mainly based on endoscopically obtained biopsies.

Prolonged red cell aplasia after major ABO-incompatible allogeneic hematopoietic stem cell transplantation: removal of persisting isohemagglutinins with Ig-Therasorb immunoadsorption.

Delayed donor red cell engraftment and prolonged red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible myeloablative and non-myeloablative hematopoietic stem cell transplantation (HSCT). There is an intense debate about the impact on outcome, severity of hemolysis, association with graft-versus-host disease and survival after blood group-incompatible stem cell transplantation. Therefore, therapeutic strategies should be considered to avoid these possible complications. We present five patients, who received allogeneic HSCT from human leukocyte antigen-identical donors for hematological malignancies, which were treated with Ig-Therasorb immunoadsorption (five treatments/week) to remove persisting incompatible isohemagglutinins. After a median of 17 treatments (range 9-25), all the patients became transfusion independent with the presentation of donor's blood group. No side effects occurred during treatment. Ig-Therasorb immunoadsorption seems to be a promising therapeutic method for rapid, efficient and safe elimination for persisting isohemagglutinins for patients with PRCA after allogeneic hematological stem cell transplantation.