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Objectives To determine the inpatient management for patients with acute idiopathic facial palsy (IFP) in Thuringia, Germany. Design Population-based study. Setting All inpatients with IFP in all hospitals with departments of otolaryngology and neurology in 2012 in the German federal state Thuringia. Main outcome measures Patients’ characteristics and treatment were compared between departments, and the probability of recovery was tested. Results 291 patients were mainly treated in departments of otolaryngology (55%) and neurology (36%). Corticosteroid treatment was the predominant therapy (84.5%). The probability to receive a facial nerve grading (Odds ratio [OR] =12.939; 95% confidence interval [CI] = 3.599 to 46.516), gustatory testing (OR = 6.878; CI =1.064 to 44.474), and audiometry (OR = 32.505; CI = 1.485 to 711.257) was significantly higher in otolaryngology departments, but lower for cranial CT (OR = 0.192; CI = 0.061 to 0.602), CSF examination (OR = 0.024; CI = 0.006 to 0.102). 131 patients (45%) showed a recovery to House-Brackmann grade ≤II. A pathological stapedial reflex test (Hazard ratio [HR] = 0.416; CI = 0.180 to 0.959) was the only independent diagnostic predictor of worse outcome. Prednisolone dose >500 mg (HR = 0.579; CI 0.400 to 0.838), and no adjuvant physiotherapy (HR = 0.568; CI = 0.407 to 0.794) were treatment-related predictors of worse outcome. Conclusions Inpatient treatment of IFP seems to be highly variable in daily practice, partly depending on the treating discipline, and despite the availability of evidence-based guidelines. The population-based recovery rate was worse than reported in clinical trials. This article is protected by copyright. All rights reserved.

The nuclear morphology of neutrophils depends on different endogenous and exogenous factors, which can lead to hypo- or hypersegmentation of the normally 2-4 segmented nucleus. Hyposegmentation can be due to mutations in the LBR-gene (Pelger-Huet-Anomaly) or can be induced, for example, by colchicine treatment. The range of this phenotypic variation is known as "norm of reaction," which can be of major relevance for clinical diagnosis and therapeutic intervention. In this project, we studied the norm of reaction in 26 subjects with 0-3 wild type LBR alleles. In addition, the phenotypic variation was analyzed in 3 patients with Familial Mediterranean Fever (FMF), before and after colchicine treatment. We measured the phenotype nuclear segmentation of neutrophils based on two conventional qualitative methods, the "rule of threads" and the "rule of thirds." In addition, we tested a morphometric quantitative approach, the "circularity index." The circularity index was superior in cases with hyposegmentation; the rule of thirds with respect to hypersegmentation. Approximately 65% of the observed phenotypic variance was explainable by the number of LBR wild type alleles. The gene-dosage effect followed a non-additive, hysteresis-like characteristic with lower and upper plateaus. Colchicine treatment had a clear, although minor phenotypic effect compared to the number of LBR wild type genes or the mutation type. Thus, the nuclear morphology of granulocytes and its norm of reaction can be regarded as an excellent model both for detailing the interplay between endogenous and exogenous factors and for clinical diagnostic purposes. © 2016 International Clinical Cytometry Society.

Background Colony‐stimulating factor 1 receptor is a tyrosine kinase transmembrane protein that mediates proliferation, differentiation, and survival of monocytes/macrophages and microglia. CSF1R gene mutations cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an autosomal‐dominantly inherited microgliopathy, leading to early onset dementia with high lethality. Methods By interdisciplinary assessment of a complex neuropsychiatric condition in a 44‐year old female patient, we narrowed down the genetic diagnostic to CSF1R gene sequencing. Flow cytometric analyses of uncultivated peripheral blood monocytes were conducted sequentially to measure the cell surface CSF1 receptor and autophosphorylation levels. Monocyte subpopulations were monitored during disease progression. Results We identified a novel heterozygous deletion–insertion mutation c.2527_2530delinsGGCA, p.(Ile843_Leu844delinsGlyIle) in our patient with initial signs of HDLS. Marginally elevated cell surface CSF1 receptor levels with increased Tyr723 autophosphorylation suggest an enhanced receptor activity. Furthermore, we observed a shift in monocyte subpopulations during disease course. Conclusion Our data indicate a mutation‐related CSF1R gain‐of‐function, accompanied by an altered composition of the peripheral innate immune cells in our patient with HDLS. Since pharmacological targeting of CSF1R with tyrosine kinase inhibitors prevents disease progression in mouse models of neurodegenerative disorders, a potential pharmacological benefit of CSF1R inhibition remains to be elucidated for patients with HDLS.

Introduction Familial amyloid polyneuropathy (FAP) is the most common subtype of hereditary amyloidosis. The amyloid protein transthyretin deposits as rigid amyloid fibers in the extracellular matrix of various tissues including peripheral nerves, heart, and gastrointestinal tract. As the mutated amyloid protein is mainly produced in the liver, one form of treatment to halt the progression of disease is liver transplantation (LT). This study was performed to identify risk factors for decreased overall survival. Methods Clinical data of 21 transplant patients who underwent LT for FAP between 1996 and 2011 were analyzed retrospectively. Results The majority of patients had cardiac symptoms (76%), gastrointestinal symptoms (71%), or peripheral polyneuropathy (71%). A conventional operating technique was performed on 11 patients using end-to-end caval anastomoses, while the modified piggyback technique by Belghiti was performed on 10 patients. Overall survival analysis revealed a one-yr survival rate of 74.3% and three- and five-yr survival rates of 60.0% and 52.5%, respectively. Pre-operative modified body mass index (mBMI)

Hoffmann K, Hinz U, Hillebrand N, Radeleff BA, Ganten TM, Schirmacher P, Schmidt J, Buchler MW, Schemmer P. Risk factors of survival after liver transplantation for HCC: a multivariate single-center analysis. Clin Transplant 2011: 25: E541–E551. © 2011 John Wiley & Sons A/S. Abstract: Background: The selection criteria for liver transplantation (LT) in patients with hepatocellular cancer (HCC) are well defined. Increasing evidence suggests that the effectiveness of pre-transplant bridging influences the individual course after LT significantly. Thus, the aim of this study was to determine its impact on tumor progression during waiting time and identify patient subgroups with favorable oncological long-term outcome. Methods: Prospectively collected data of 78 consecutive patients undergoing LT for HCC between 2001 and 2007 were analyzed retrospectively. Survival rates were assessed using the Kaplan–Meier estimate. Clinicopathologic prognostic factors were identified by Cox regression analysis. Results: After 48.9 months of median follow-up, the five-yr overall survival rate is 57% with a five-yr recurrence-free survival rate of 74%. Progressive disease (PD) during bridging was developed in 32% of patients, and a trend toward impaired overall survival in patients with PD before LT was detected in multivariate analysis (p = 0.073). HCC ≥3 cm was associated with a three times increased risk of recurrent disease. Neither fulfillment of MILAN criteria nor bridging with transarterial chemoembolization had an impact on the outcome. Conclusion: PD during waiting time influences the oncological course after LT. However, even with an increasing organ shortage, further studies are warranted to define clear selection criteria based on the biological tumor behavior and allow a more personalized treatment.

Purpose: Frequent epileptic seizures or prolongedseizureactivity (status epilepticus, SE) isknowntoincrease the brain expression of drug efflux trans-porter genes and proteins, such as P-glycoprotein(Pgp) and members of the multidrug resistanceprotein (MRP) family, which might reduce brainlevels of antiepileptic drugs and, therefore, beinvolved in drug resistance. However, the timecourse of alterations in Pgp or MRPsafterseizuresorSEisonlyincompletelyknown.Methods: This prompted us to study the timecourse of alterations in the expression of differentefflux transporter genes (Mdr1a, Mdr1b, MRP1,MRP2, MRP5) at various times after a pilocarpine-induced SE in limbic brain regions, usingquantitative real-time polymerase chain reaction(RT-PCR)(qPCR).Results: Unexpectedly, between 6 and 24 h afteronset of SE, genes encoding Pgp (Mdr1a, Mdr1b),Mrp1, and Mrp5 were downregulated in hippo-campus, amygdala, or piriform cortex. This initialdecrease in expression was followed by normali-zation and then increased expression, whichbecame maximal 2 days after SE. One explana-tion for the initial decrease in transporter expres-sion could be SE-induced acute inflammatoryprocesses, because proinflammatory cytokinesare known to suppress the expression of Pgp andother efflux transporters. To directly address thispossibility, we quantified the hippocampal mRNAexpression of interleukin-1b, interleukin-6, andtumor necrosis factor-a, showing a markedSE-induced increase in these cytokines, whichparalleled the decreased expression of effluxtransporters.Discussion: Taken together, these findings indi-cate that alterations in expression of drug effluxtransporters after prolonged seizure activity aremorecomplexthanpreviouslythought.KEY WORDS: P-glycoprotein, Multidrug resis-tant proteins, Cytokines, Cyclooxygenase-2,Inflammation,Seizures.Active drug efflux transporters of theATP-binding cas-sette (ABC) family, such as P-glycoprotein (Pgp; MDR1;ABCB1) or members of the multidrug resistance protein(MRP; ABCC) family, play important roles in regulatingdrug concentrations in various cells and tissues, includingthe brain (Schinkel & Jonker, 2003). In the brain, suchtransporters are expressed at the blood–brain barrier(BBB) and by parenchymal cells such as astrocytes,affecting the brain disposition and hence clinical efficacyof a variety of drugs (Begley, 2004). In antiepileptic drug(AED) resistant epilepsy, particularly temporal lobe epi-lepsy, an overexpression of Pgp and several MRPs hasbeen determined in epileptogenic brain tissue resectedduring epilepsy surgery (Kwan & Brodie, 2005; Lcscher& Potschka, 2005a, 2005b; Tate & Sisodiya, 2007). Thislocalized overexpression of efflux transporters has beenproposed to reduce the penetration of AEDs into thebrain and thereby contribute to AED resistance, but this

Orthotopic liver transplantation has been made feasible with intra-operative femoral-to-jugular veno-venous bypass (VVB) to redirect the blood from the lower extremities and the kidneys to the heart. This reduces hemodynamic instability and metabolic disturbances. However, complications such as thromboses with pulmonary thrombembolism or post-reperfusion syndrome were observed in up to 30% of the cases. The latter, recent developments of cava-sparing surgical techniques, shorter anhepatic times plus optimized anesthetic management have made the necessity for a routine use of VVB questionable.

Plasma-chemically tailor-made polymer surfaces are of ever-increasing importance to control surface properties in material science, as well as for (bio)analytical and biomedical applications. For the characterization of such systems, sensitive fluorescence techniques are attractive tools. To underline the potential and drawbacks of these strategies, this article addresses different problems that complicate fluorometric analysis. To overcome some of these limitations, such as nonspecific adsorption of unreacted fluorescent probes, we discuss potential troubleshooting, including the use of a chromogenic and fluorogenic pyrylium dye for the detection of amino functionalities at polypropylene surfaces.

Despite high cure rates 25% of children with acute lymphoblastic leukaemia (ALL) relapse and have dismal outcome. Crucially, many are currently stratified as standard risk (SR) and additional markers to improve patient stratification are required. Here we have used diagnostic bone marrow specimens from 101 children with pre-B ALL to examine the use of gene expression profiles (GEP) as predictors of long-term clinical outcome. Patients were divided into two cohorts for model development and validation based on availability of specimen material. Initially, GEP from 55 patients with sufficient material were analysed using HG-U133A microarrays, identifying an 18-gene classifier (GC) that was more predictive of outcome than conventional prognostic parameters. After feature selection and validation of expression levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR), a three-gene qRT-PCR risk index [glutamine synthetase (GLUL), ornithine decarboxylase antizyme inhibitor (AZIN), immunoglobulin J chain (IGJ)] was developed that predicted outcome with an accuracy of 89% in the array cohort and 87% in the independent validation cohort. The data demonstrate the feasibility of using GEP to improve risk stratification in childhood ALL. This is particularly important for the identification of patients destined to relapse despite their current stratification as SR, as more intensive front-line treatment options for these individuals are already available.

Excessive skin wrinkling and cutis laxa are seen in many genetic conditions and overlapping features can make a clinical diagnosis difficult. Here we report on 22 Omani patients from 11 consanguineous families with the diagnosis of wrinkly skin syndrome (WSS, OMIM 278250) or geroderma osteodysplasticum hereditaria (GO, OMIM 231070). The WSS phenotype evolves during early childhood and includes a generalized and excessive skin wrinkling, dental problems, herniae, foot deformities, hip dislocations, growth retardation, and a large anterior fontanelle. The facial gestalt is characterized by a broad nasal bridge, hypertelorism, and downslanting palpebral fissures. We were unable to differentiate between WSS and cutis laxa with growth and developmental delay (CLGDD, OMIM 219200) suggesting that both can be considered as one entity. Distinct hallmarks of GO were skin wrinkling limited to the dorsum of hands and feet and to the abdomen, normal fontanelles, maxillary hypoplasia, bowed long bones, and osteopenia with frequent fractures. In contrast to the attenuation of the skin phenotype with age in WSS, adult patients with GO appeared prematurely aged. A serum sialotransferrin type 2 pattern was found in all four WSS patients tested. Apolipoprotein CIII (a marker for O-glycosylation) was normal suggesting that WSS is frequently associated with a N-protein glycosylation defect, probably at the level of processing (CDG-II). All four investigated GO patients showed normal sialotransferrin patterns. The known loci for cutis laxa and WSS on 2q31, 5q23-q31, 7q11, 11q13, and 14q32 were excluded. We suggest that WSS and GO are distinct entities with overlapping features. © 2008 Wiley-Liss, Inc.

In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

Summary The increasing complexity of hepato-biliary surgery, including major hepatic resections and living donor liver transplantation (LDLT), has lead to an increasing demand for sophisticated imaging modalities. Standard operation planning for hepatic resections and preoperative donor and recipient work-up for LDLT is based on two-dimensional computed tomography (CT) images and magnetic resonance imaging. However, even modern multidetector CT scanners are not able to perform routinely three-dimensional (3D) visualization needed for operation planning in liver surgery or LDLT. As a consequence, special-purpose computer-based operation planning systems have been developed that leverage the possibilities of modern image processing to improve surgical planning. The advances in technology enable surgeons to analyse and to visualize the anatomy of the human liver including the vascular structures within the human liver and define the exact volumetric data of the liver tissue to be resected or preserved. Furthermore, 3D visualization of the vessel architecture within the human liver allows a reliable estimation of the amount of liver tissue that could be at risk after resection because of inadequate hepatovenous drainage. Because of its clinical usefulness and real-time visualization capabilities we already use an operation planning system in selected patients prior to liver resection and before donor hepatectomy for LDLT as a standard.

Cf Article en Anglais dans Chemical Engineering & Technology, 1998, Vol 21, No 5, pp. 408-412.

We present a case of balloon angioplasty of the superficial femoral artery via a popliteal artery access with successful percutaneous vascular closure of the vascular access site (6-F Techstar). A femoral arterial approach had not been feasible due to previous aorto-femoral and femoro-femoral bypass operations. Clinical and ultrasound follow-up showed no complications up to 3 months after remote suturing.

The combination of nanomaterials as solid supports and supramolecular concepts has led to the development of hybrid materials with improved functionalities. These "hetero-supramolecular" ideas provide a means of bridging the gap between molecular chemistry, materials sciences, and nanotechnology. In recent years, relevant examples have been reported on functional aspects, such as enhanced recognition and sensing by using molecules on preorganized surfaces, the reversible building of nanometer-sized networks and 3D architectures, as well as biomimetic and gated chemistry in hybrid nanomaterials for the development of advanced functional protocols in three-dimensional frameworks. This approach allows the fine-tuning of the properties of nanomaterials and offers new perspectives for the application of supramolecular concepts.