Microsurgical clipping as a retreatment strategy for previously ruptured aneurysms treated with the Woven EndoBridge (WEB) device: a mono-institutional case series.

BACKGROUND: Since its approval by the US Food and Drug Administration (FDA) in 2018, the flow disruptor Woven EndoBridge (WEB) device has become increasingly popular for the endovascular treatment of unruptured and ruptured cerebral aneurysms. However, the occlusion rates seem rather low and the retreatment rates rather high compared to other treatment methods. For initially ruptured aneurysms, a retreatment rate of 13 % has been reported. A variety of retreatment strategies has been proposed; however, there is a paucity of data concerning microsurgical clipping of WEB-pretreated aneurysms, especially previously ruptured ones. Thus, we present a single-center series of five ruptured aneurysms treated with the WEB device and retreated with microsurgical clipping. METHODS: A retrospective study including all patients presenting with a ruptured aneurysm undergoing WEB treatment at our institution between 2019 and 2021 was performed. Subsequently, all patients with an aneurysm remnant or recurrence of the target aneurysm retreated with microsurgical clipping were identified. RESULTS: Overall, five patients with a ruptured aneurysm treated with WEB and retreated with microsurgical clipping were included. Besides one basilar apex aneurysm, all aneurysms were located at the anterior communicating artery (AComA) complex. All aneurysms were wide-necked with a mean dome-to-neck ratio of 1.5. Clipping was feasible and safe in all aneurysms, and complete occlusion was achieved in 4 of 5 aneurysms. CONCLUSIONS: Microsurgical clipping for initially ruptured WEB-treated aneurysms is a feasible, safe, and effective treatment method in well-selected patients.

Quantitation of plasmatic lysosphingomyelin and lysosphingomyelin-509 for differential screening of Niemann-Pick A/B and C diseases.

Acid sphingomyelinase deficiency (ASMd, Niemann-Pick disease A/B) and Niemann-Pick type C disease (NPC) share core clinical symptoms. Initial diagnostic discrimination of these two rare lysosomal storage diseases is thus difficult. As sphingomyelin accumulates in ASMd as well as NPC, lysosphingomyelin (sphingosylphosphorylcholine) and its m/z 509 analog were suggested as biomarkers for both diseases. Herein we present results of simultaneous LC-ESI-MS/MS measurements of lysosphingomyelin and lysosphingomyelin 509 in plasma and dried blood spots (DBS) collected from ASMd and NPC patients and suggest that the plasma but not DBS levels of the two analytes allow differential biochemical screening of ASMd and NPC.

A prospective study in children with a severe form of atopic dermatitis: clinical outcome in relation to cytokine gene polymorphisms.

BACKGROUND AND OBJECTIVE: The course of atopic dermatitis (AD) in childhood is characterized by typical changes in phenotype, including a shift from skin involvement to respiratory allergy usually around the third year of age. We thus designed a prospective study to monitor the outcome of severe AD and to investigate the association between cytokine gene polymorphisms and clinical manifestations. METHODS: Clinical and laboratory follow-up of 94 patients with severe AD and 103 healthy controls was performed using routine methodology. Allele, genotype, and haplotype frequencies of single nucleotide polymorphisms of 13 selected cytokine/receptor genes were analyzed using PCR with sequence-specific primers. RESULTS: In our study, genotypes of 7 polymorphisms--LL-4 -1098G/T and -590C/T, IL-6 -174C/G and nt565A/G, and IL-10 -1082A/G, -819C/T, and -592A/C were significantly associated with atopic AD (P < .05). A significant association was also found for TNF-alpha AA and IL-4 GC haplotypes and AD. We confirm the progressive clinical improvement of AD together with a decrease in the severity index SCORAD (SCORing atopic dermatitis) during childhood (P < .05). We found significant differences between IL-4Ralpha +1902 A/G and positivity of tree pollen-specific IgE (P < .05) in the AD group. Moreover, a weak association was also found between IL-10 -819C/T and IL-10 -590A/C and the appearance of allergic rhinitis (P < 0.1). CONCLUSIONS: We confirmed a clinical shift in allergic phenotype in the first 3 years of life, and showed an association between IL-4, IL-6, and IL-10 polymorphisms and AD. Our data indicate that IL-4alpha and IL-10 polymorphisms may be considered predictive factors of respiratory allergy in children with AD.

Impact of Implementing an Elaborated CT Perfusion Protocol for Aneurysmal SAH on Functional Outcome: CTP Protocol for SAH.

BACKGROUND AND PURPOSE: The acute phase of aneurysmal SAH is characterized by a plethora of impending complications with the potential to worsen patients' outcomes. The aim of this study was to evaluate whether an elaborated CTP-based imaging protocol during the acute aneurysmal SAH phase is able to prevent delayed infarctions and contribute to a better outcome. MATERIALS AND METHODS: In 2012, an elaborated CTP-based protocol was implemented for the management of patients with aneurysmal SAH. Retrospective analysis of patients with aneurysmal SAH treated from 2010 to 2013 was performed, comparing the patients treated before (group one, 2010-2011) with those treated after the protocol implementation (group two, 2012-2013) with regard to delayed infarctions and outcome according to the mRS at 3-months' follow-up. RESULTS: A total of 133 patients were enrolled, of whom 57 were included in group 1, and 76, in group 2. There were no significant differences between the groups concerning baseline characteristics. In the multivariate analysis, independent predictors of a good outcome (mRS ≤ 2) were younger age (P < .001), lower World Federation of Neurosurgical Societies grade (P < .001), absence of delayed infarction (P = .01), and management according to the CTP protocol (P = .01). Larger or multiple infarctions occurred significantly more often in group 1 compared with group 2 (88% versus 33% of all delayed infarctions, P = .03). The outcome in group 2 was significantly better compared with group 1 (P = .005). CONCLUSIONS: The findings suggest that implementation of an elaborated CTP protocol is associated with a better outcome. An earlier initiation of further diagnostics and treatment with prevention of large territorial and/or multiple infarctions might have led to this finding.

Serum immunoglobulin free light chains in severe forms of atopic dermatitis.

An increase in immunoglobulin free light chains (FLC) was recently described in several pathological conditions, including asthma. FLC pathology is classically associated with monoclonal gammopathies. Its association with allergic disorders is surprising and unexplained. We therefore tested a cohort of children with severe atopic dermatitis (SCORAD 50-80) to determine the serum levels of free kappa and lambda chains, and correlated the results with clinical status and relevant laboratory markers. Seventy-three patients with severe forms of AD, all children from 3 months to 3 years of age and ninety healthy age-matched controls were included in the study. Light chains in sera were tested using the Freelite assay (Binding Site, Birmingham, UK). There were highly significant differences in both kappa (mean: 7.05 and 3.22 mg/l) and lambda (mean: 10.99 and 9.8 mg/l) serum levels between patients and controls, respectively (P < 0.0001). The kappa/lambda ratio in patients with allergy (mean: 0.64) was significantly higher than in controls (0.33) (P < 0.0001). We further observed significantly increased levels of FLC and their ratio in the group of patients with severe forms of AD in comparison to the group of patients with a resting stage of the disease or healthy controls (P < 0.05 and P < 0.0001, respectively). On the other hand, we could not confirm any association of FLC levels with age or total IgE levels. In conclusion, an increase in FLC reflects disease activity in children with severe atopic dermatitis. FLC might thus represent an additional diagnostic marker independent of total IgE levels.

Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process.

We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickness followed by sepsis, disseminated intravascular coagulation, and multiorgan failure. She succumbed to a cerebral haemorrhage. Autopsy revealed liver cholestatic cirrhosis and multifocal liver carcinoma with immunophenotype compatible with cholangiocarcinoma. Analysis of the storage process revealed its absence or very low levels in the majority of liver and spleen macrophages. Gaucher cells (GCs) were seen only as occasional aggregates of various sizes in these organs. GCs were seen also in the leptomeninx of the cerebellum and as infrequent perivascular clusters in both the grey and white cerebral matters. Bone marrow was heavily infiltrated with GCs, especially in the adipocyte-rich part. GCs in this location displayed varied degrees of cytoplasmic vacuolation unrelated to the lysosomal compartment, caused by droplets of triglyceride, and interpreted as due to resorption of fragments of altered white adipocytes. All these observations point to the relative efficacy of ERT in covering the standard substrate load, which should not be exceeded as it would lead to the evolution of mature GCs. The results are discussed in relation to our recently published hypothesis on GD cell pathology.

Unenhanced Time-of-Flight MR Angiography versus Gadolinium-Enhanced Time-of-Flight MR Angiography in the Follow-Up of Coil-Embolized Aneurysms.

Background and Purpose Coil embolization of ruptured and unruptured aneurysms has emerged as a widely accepted alternative to clipping. Unfortunately, coil-embolized aneurysms need a long-term imaging follow-up to confirm the stability of the occlusion status. We investigated whether contrast-enhanced time-of-flight (ToF) magnetic resonance angiography (MRA) (gadolinium [Gd]-ToF) provides any diagnostic benefit over conventional ToF MRA (nonenhanced [NE]-ToF) in this context. Material and Methods From October 2013 to January 2015, all patients who were regularly scheduled for their follow-up after coil embolization were examined with Gd-ToF and NE-ToF angiography. The general visibility of the occlusion result was compared between the two MRAs as well as with the last digital subtraction angiography (DSA) available. Subgroups of interest (follow-up after stent-assisted coil embolization, cases with already known aneurysm remnants) were also analyzed. Results A total of 70 patients (44 female) harboring 74 treated aneurysms were examined. The reproducibility of the DSA result in terms of therapeutic relevance was 100%. In 10 of 74 cases (14%), the aneurysm status was more difficult to judge in the NE-ToF images (p = 0.02), and the visualization of small vessels was significantly better in the Gd-ToF (p = 0.003). NE-ToF did not fail to show any aneurysm remnants but were more difficult to depict in 35% of the cases (p = 0.09). Regarding the aneurysms that were coiled with stent assistance, there was no significant difference in terms of the visualization (p = 0.1). Conclusion Gd-ToF angiography is in general not superior to NE- ToF for the follow-up of coil-embolized aneurysms.

[Enzyme therapy in children with severe forms of Gaucher's disease]. / Enzymová terapie u detí s tezkou formou Gaucherovy nemoci.

The enzyme therapy with Ceredase in patients with Gaucher's disease is at present probably the most expensive treatment in the whole world. One-year treatment of an adult patient with Gaucher's disease costs more than 7 million crowns. Indications for treatment in individual patients as well as financial provisions are so far problematic in the Czech Republic. From a total of 28 patients of varying age with Gaucher's disease diagnosed by the authors Ceredase was administered to two boys with a severe course of the disease. Within one year of treatment the health status of both children improved, growth became normal, the spleen diminished in size by 20-35%, haematological manifestations of hypersplenism are receding, there was a 32-46% decline of the activity of serum chitotriosidase and biochemical parameters of the disease improved.

Volume perfusion CT (VPCT) for the differential diagnosis of patients with suspected cerebral vasospasm: qualitative and quantitative analysis of 3D parameter maps.

OBJECT: Cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) implies high risk for secondary ischemia. It requires early diagnosis to start treatment on time. We aimed to assess the utility of "whole brain" VPCT for detecting localization and characteristics of arterial vasospasm. METHODS: 23 patients received a non-enhanced CT, VPCT and CTA of the brain. The distribution of ischemic lesions was analyzed on 3D-perfusion-parameter-maps of CBF, CBV, MTT, TTS, TTP, and TTD. CT-angiographic axial and coronal maximum-intensity-projections were reconstructed to determine arterial vasospasm. CT-data was compared to DSA, if performed additionally. Volume-of-interest placement was used to obtain quantitative mean VPCT values. RESULTS: 82% patients (n=19) had focal cerebral hypoperfusion. 100% sensitivity and 100% specificity was found for TTS (median 1.9s), MTT (median 5.9s) and TTD (median 7.6s). CBV showed no significant differences. In 78% (n=18) focal vessel aberrations could be detected either on CTA or DSA or on both. CONCLUSION: VPCT is a non-invasive method with the ability to detect focal perfusion deficits almost in the whole brain. While DSA remains to be the gold standard for detection of CV, VPCT has the potential to improve noninvasive diagnosis and treatment decisions.

Synthetic biology, inspired by synthetic chemistry.

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell.

[A case of Pelger-Huet anomaly in a premature infant]. / Erworbene Pelger-Huëtsche Anomalie bei einem Frühgeborenen.

The report deals with a prematurely born child affected with multilateral anomalies of body development, defect of cell immunity and acquired Pelger-Huët's anomaly. Pelger-Huët's anomaly was detected in a blood smear during the third week of life by an extreme deviation to the left, the degree of which fluctuated, however, depending on the reiterating exacerbations of the infect. The morphological changes of blood elements persisted until exitus letalis in a severe respiratory infect. The changes of the karyotype and possible relations to Pelger-Huët's anomaly and malformations of development are discussed in detail.