Superficial fibromas with CTNNB1 mutation.

Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.

Improved glycaemic control and treatment satisfaction with a simple wearable 3-day insulin delivery device among people with Type 2 diabetes.

AIM: To evaluate the PAQ® (CeQur SA, Horw, Switzerland), a wearable 3-day insulin delivery device that provides set basal rates and bolus insulin on demand, in people with Type 2 diabetes. METHOD: Adults with Type 2 diabetes with HbA1c concentrations ≥53 and ≤97 mmol/mol (7.0 and 11.0%) while treated with ≥2 insulin injections/day were enrolled in two single-arm studies comprising three periods: a baseline (insulin injections), a transition and a PAQ treatment period (12 weeks). Endpoints included HbA1c , seven-point self-monitored blood glucose, total daily dose of insulin and body weight. Safety was assessed according to examination, hypoglycaemic episodes and adverse device effects. RESULTS: A total of 28 adults were enrolled (age 63 ± 7 years, 86% men, BMI 32.3 ± 4.3kg/m2 , Type 2 diabetes duration 17 ± 8 years, HbA1c 70 ± 12 mmol/mol (8.6 ± 1.1%), total daily insulin dose 58.7 ± 20.7 U), of whom 24 completed the studies. When transitioned to PAQ, 75% of participants continued on the first basal rate selected. After 12 weeks of PAQ wear, significant improvements from baseline were seen [HbA1c -16 ± 9 mmol/mol (95% CI -20, -12) or -1.5 ± 0.9% (95% CI -1.8, -1.1) P<0.0001], and at all seven self-monitored blood glucose readings time points (P ≤0.03). Total daily insulin dose increased by 12.1 ± 19.5 U (95% CI 3.9, 20.4; P=0.0058), the number of meal time boluses increased by 0.9 ± 1.5/day (95% CI 0.3, 1.5; P=0.0081) and body weight remained stable. Six participants had mild to moderate catheter site reactions and one mild skin irritation occurred. No participant experienced severe hypoglycaemia. CONCLUSIONS: Adults with Type 2 diabetes were safely transitioned from insulin injections to the PAQ and had significantly improved glycaemic control and treatment satisfaction with insulin therapy. (ClinicalTrials.gov identifiers: NCT02158078 & NCT02419859).

Body fluid identification using a targeted mRNA massively parallel sequencing approach - results of a EUROFORGEN/EDNAP collaborative exercise.

In a previous study we presented an assay for targeted mRNA sequencing for the identification of human body fluids, optimised for the Illumina MiSeq/FGx MPS platform. This assay, together with an additional in-house designed assay for the Ion Torrent PGM/S5 platform, was the basis for a collaborative exercise within 17 EUROFORGEN and EDNAP laboratories, in order to test the efficacy of targeted mRNA sequencing to identify body fluids. The task was to analyse the supplied dried body fluid stains and, optionally, participants' own bona fide or mock casework samples of human origin, according to specified protocols. The provided primer pools for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms included 33 and 29 body fluid specific targets, respectively, to identify blood, saliva, semen, vaginal secretion, menstrual blood and skin. The results demonstrated moderate to high count values in the body fluid or tissue of interest with little to no counts in non-target body fluids. There was some inter-laboratory variability in read counts, but overall the results of the laboratories were comparable in that highly expressed markers showed high read counts and less expressed markers showed lower counts. We performed a partial least squares (PLS) analysis on the data, where blood, menstrual blood, saliva and semen markers and samples clustered well. The results of this collaborative mRNA massively parallel sequencing (MPS) exercise support targeted mRNA sequencing as a reliable body fluid identification method that could be added to the repertoire of forensic MPS panels.

Use of glucagon-like peptide-1 receptor agonists among individuals on basal insulin requiring treatment intensification.

As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon-like peptide-1 receptor agonists and insulin, which may be added on to oral glucose-lowering treatments. Among individuals receiving long-acting basal insulin as their first injectable treatment, ~40-60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short-acting prandial insulin or a glucagon-like peptide-1 receptor agonist. Glucagon-like peptide-1 receptor agonists vary in their effects, with short- and long-acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon-like peptide-1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon-like peptide-1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon-like peptide-1 receptor agonist and basal insulin, fixed-ratio combinations of a glucagon-like peptide-1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long-term glycaemic control.

[Gastrointestinal stromal tumors of the stomach and precursor lesions]. / Gastrointestinale Stromatumoren des Magens und ihre Vorstufen.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract although they are much less frequent than epithelial tumors. In more than 60% of cases they occur in the stomach. Especially small lesions measuring ≤1 cm in diameter, so-called microscopic GIST can occur multifocally, frequently in the proximal stomach wall and sometimes as an incidental finding in a gastrectomy specimen resected for gastric cancer. The multicentricity of GIST alone is not proof of a metastatic behavior or a syndromal or hereditary disease. Multiple sporadic synchronous and metachronous GIST are characterized by different primary mutations mostly in the KIT or PDGFRA genes and are often less aggressive. It is speculative whether a field effect is responsible or whether still unknown GIST-promoting factors may facilitate the development of several independent lesions. If KIT or PDGFRA mutations are lacking, a succinate dehydrogenase (SDH) deficient GIST has to be considered, either hereditary as Carney-Stratakis syndrome or syndromal as part of a Carney triad.

Not only age but also tactile perception influences the preference for cosmetic creams applied to the forearm.

OBJECTIVE: We aimed to examine whether and how age as well as tactile sensitivity and perception had an impact on how women liked richer and lighter creams. Furthermore, the question arose if age and tactile perception had an influence on the ability to distinguish between the creams and how the ability to distinguish between creams influenced the liking of these creams. METHODS: A total of 299 female participants were invited to rate how much they liked four different cosmetic creams applied to their forearms. The creams were based on the same base formula but differed with respect to the texture. In order to arouse the impression of more lightness (quasi-light) or more richness (quasi-rich), polyethylene particles of different sizes were added to the base formula. First of all, the participants were tested for their tactile sensitivity and perception. Tactile sensitivity was tested by Von Frey filaments, tactile spatial perception by the tactile Landolt ring test and the ability to discriminate surface structures by a sandpaper test. Furthermore, the participants rated the creams with respect to the acceptance, the subjective skin feeling after application and performed paired-comparison tests. Analyses of variance and regression analyses were applied to the data. RESULTS: In general, participants liked quasi-rich creams less than quasi-light creams. However, older women compared to younger women and women with lower tactile performance in comparison with women with higher tactile performance revealed a weaker influence of cream type-specific acceptance ratings. Further results revealed that young participants perceived the quasi-light creams (with particles of ~50 µm diameter) as soft and quasi-rich creams (with particles of ~100 µm and ~165 µm diameter), as coarse. In contrast, this subjective skin feeling after application in participants at age 50 and older did not differ much. CONCLUSION: Age and tactile perceptual abilities have additive effects on the acceptance of creams with different textures when applied to the forearm.

Observation and Structure Determination of an Oxide Quasicrystal Approximant.

We report on the first observation of an approximant structure to the recently discovered two-dimensional oxide quasicrystal. Using scanning tunneling microscopy, low-energy electron diffraction, and surface x-ray diffraction in combination with ab initio calculations, the atomic structure and the bonding scheme are determined. The oxide approximant follows a 3^{2}.4.3.4 Archimedean tiling. Ti atoms reside at the corners of each tiling element and are threefold coordinated to oxygen atoms. Ba atoms separate the TiO_{3} clusters, leading to a fundamental edge length of the tiling 6.7 Å.

Understanding surface reactivity of Si electrodes in Li-ion batteries by in operando scanning electrochemical microscopy.

In operando SECM is employed to monitor the evolution of the electrically insulating character of a Si electrode surface during (de-)lithiation. The solid-electrolyte interface (SEI) formed on Si electrodes is shown to be intrinsically electrically insulating. However, volume changes upon (de-)lithiation lead to the loss of the protecting character of the initially formed SEI.

XMCD studies of thin Co films on BaTiO3.

Different layer thicknesses of cobalt ranging from 2.6 Å (1.5 ML) up to 55 Å (30.5 ML) deposited on ferroelectric BaTiO3 have been studied regarding their magnetic behavior. The layers have been characterized using XMCD spectroscopy at remanent magnetization. After careful data analysis the magnetic moments of the cobalt could be determined using the sum rule formalism. There is a sudden and abrupt onset in magnetism starting at thicknesses of 9 Å (5 ML) of cobalt for measurements at 120 K and of 10 Å (5.5 ML) if measured at room temperature. Initial island growth and subsequent coalescence of Co on BaTiO3 is suggested to explain the sudden onset. In that context, no magnetically dead layers are observed.

SS18-SSX fusion protein-induced Wnt/ß-catenin signaling is a therapeutic target in synovial sarcoma.

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/ß-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/ß-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear ß-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/ß-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/ß-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/ß-catenin protein-protein interaction significantly blocked the canonical Wnt/ß-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/ß-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/ß-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies.

Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment.

AIMS: Antibody formation to therapeutic peptides is common. This analysis characterizes the time-course and cross-reactivity of anti-exenatide antibodies and potential effects on efficacy and safety. METHODS: Data from intent-to-treat patients in 12 controlled (n = 2225,12-52 weeks) and 5 uncontrolled (n = 1538, up to 3 years) exenatide twice-daily (BID) trials and 4 controlled (n = 653,24-30 weeks) exenatide once weekly (QW) trials with 1 uncontrolled period (n = 128,52 weeks) were analysed. RESULTS: Mean titres peaked early (6-22 weeks) and subsequently declined. At 30 weeks, 36.7% of exenatide BID patients were antibody-positive; 31.7% exhibited low titres (≤125) and 5.0% had higher titres (≥625). Antibody incidence declined to 16.9% (1.4% higher titre) at 3 years. Similarly, 56.8% of exenatide QW patients were antibody-positive (45.0% low/11.8% higher titre) at 24-30 weeks, declining to 45.4% positive (9.2% higher titre) at 52 weeks. Treatment-emergent anti-exenatide antibodies from a subset of patients tested did not cross-react with human GLP-1 or glucagon. Other than injection-site reactions, adverse event rates in antibody-positive and antibody-negative patients were similar. Efficacy was robust in both antibody-negative and antibody-positive patients (mean HbA1c change: -1.0 and -0.9%, respectively, exenatide BID; -1.6% and -1.3% exenatide QW). No correlation between change in HbA1c and titre was observed for exenatide BID, although mean reductions were attenuated in the small subset of patients (5%) with higher titres. A significant correlation was observed for exenatide QW with no difference between antibody-negative and low-titre patients, but an attenuated mean reduction in the subset of patients (12%) with higher titres. CONCLUSIONS: Low-titre anti-exenatide antibodies were common with exenatide treatment (32% exenatide BID, 45% exenatide QW patients), but had no apparent effect on efficacy. Higher-titre antibodies were less common (5% exenatide BID, 12% exenatide QW) and within that titre group, increasing antibody titre was associated with reduced average efficacy that was statistically significant for exenatide QW. Other than injection-site reactions, anti-exenatide antibodies did not impact the safety of exenatide.

A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin.

AIM: To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo. METHODS: A 26-week, multi-country (Canada, Mexico, Romania, South Africa and the USA), randomized, double-blind, placebo-controlled study compared exenatide twice-daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA(1c) 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2-week, single-blind, lead-in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA(1c) change at endpoint (Week 26 or last-observation-carried-forward). RESULTS: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA(1c) significantly more than placebo [-0.84% (s.e. 0.20) vs. -0.10% (0.23), treatment difference -0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, -1.4 (s.e. 0.6) kg vs. placebo, -0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA(1c) and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups. CONCLUSIONS: Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA(1c) without associated hypoglycaemia.

Impact of a change in antibiotic prophylaxis on total antibiotic use in a surgical intensive care unit.

OBJECTIVE: The aim of this study was to evaluate the impact of reducing the length of antibiotic prophylaxis for cerebro spinal shunts on total antibiotic use and key resistant pathogens. METHODS: In January 2004, the use of antibiotic prophylaxis was reduced to a single shot dose with cefuroxime in an intensive care unit (ICU). Prior to this intervention, prophylaxis with second-generation cephalosporins was administered during the entire period of external cerebro spinal fluid (CSF) drainage. The effect on the antibiotic use density (AD: DDD [defined daily doses] per 1,000 patient-days[pd]) was calculated prior to (January 2002-December 2003) and following implementation of the intervention(January 2004-December 2006) by segmented regression analysis of an interrupted time series. Resistance proportions(RP) and resistance densities (RD), defined as resistant pathogen/1,000 pd of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis or E. faecium, third-generation-resistant (3GC) Escherichia coli and Klebsiella pneumoniae, and imipenem-resistant Pseudomonus aeruginosa, were compared by the Fisher's exact test before and after the intervention. RESULTS: Total antibiotic use by 147 DDD/1,000 pd decreased after the intervention when pre-operative prophylaxis was changed into single shot prophylaxis, from an estimated mean of 1,036 DDD/1,000 pd before the intervention to 887DDD/1,000 pd post-intervention. This decrease was primarily due to a significant reduction in the amount of cefuroxime used for prophylaxis. The reduction in total antibiotic consumption was sustainable, and it did not increase again during the next 36 months. The RR and RD of third-generation cephalosporin-resistant E. coli increased after January 2004, whereas the percentage of MRSA significantly decreased. CONCLUSION: Change to single shot prophylaxis along with an ongoing antibiotic stewardship program resulted in a cut-back in total antibiotic use amounting to as much as 15%. It would therefore appear that targeting interventions aimed at reducing antibiotic prophylaxis in surgical ICUs may be very worthwhile.

[Reservoirs of Pseudomonas aeruginosa in the intensive care unit. The role of tap water as a source of infection]. / Reservoire von Pseudomonas aeruginosa auf der Intensivstation. Die Bedeutung des Wassers als Infektionsquelle.

In spite of significant changes in the spectrum of organisms causing nocosomial infections in intensive care units (ICUs), Pseudomonas aeruginosa has held a nearly unchanged position as an important pathogen. Today, the organism is isolated as the second most frequent organism causing ventilator-associated pneumonia, and the third or fourth most frequent pathogen causing septicemia, urinary tract infections, and surgical wound infections. In the past, horizontal transmissions were regarded as the most relevant route of strain acquisition. However, during the last 10 years, a significant proportion of P. aeruginosa isolates were demonstrated to stem from ICU water sites. Studies using molecular typing techniques have shown that up to 50% (in one study 92%) of nosocomial P. aeruginosa acquisitions may result from transmission through tap water. Additional proof of concept of waterborne infection comes from the reports of three recent studies that infection rates may be lowered significantly by eliminating colonized tap water sources or interrupting transmission chains from water sites.

Maltrato entre pares o bullying: una visión actual / Abuse among partners or bullying: current concepts

An up to date on scholars abuse or "bullying" is presented. Its significance, role, characteristics, consequences and epidemiology are explained. Schools interventions and their results are reviewed and an analysis of health team role is performed. A family and patient counseling is proposed. There is a special emphasis on the witness or bystander role in schools and health interventions performed.

Se presenta una actualización sobre el acoso o maltrato escolar entre pares o "bullying". Se explica su significado, el rol y características de sus actores y sus consecuencias. Se menciona su epidemiología y los factores condicionantes que influyen en su presencia. Se revisan las intervenciones realizadas en los colegios y sus resultados, y se analiza el rol de los prestadores de salud. Se proponen indicaciones de consejería a la familia, con algunos datos útiles para usarlos en la consulta con los pacientes. Se hace especial énfasis en el rol del testigo (bystander) o espectador tanto en las intervenciones escolares realizadas, como que éste sea foco de atención en la consulta de los profesionales.

[Needleless connection valves--commentary from a clinical perspective]. / Nadelfreie Konnektionsventile und Blutstrominfektionen--Kommentar aus klinischer Sicht.

Needle-less connection valves (NFCs) for infusion systems, blood drawing- or i. v. injection ports may offer significant benefits to the patient and the attending health care workers. On the other hand, a number of recent reports described a relationship between an increased incidence density of catheter-associated infections and the introduction of certain NFCs in clinical practice. Thus, the safety of the device in terms of an effective and feasible disinfection protocol for the outer membrane and absence of unintended bacterial deposits inside the device should have been confirmed with appropriate in vitro investigations. In addition, the introduction into clinical practice should be supervised by continuously performed surveillance for catheter-associated infections. Taking these prerequisites into account, NFCs may increase the safety and feasibility of intravenous therapy using central venous catheters in high-risk patients.

Intranasal mupirocin prophylaxis in elective surgery. A review of published studies.

BACKGROUND: Mupirocin is a natural antibiotic from Pseudomonas fluorescens which is available as a 2% ointment. The drug has been used mainly for topical treatment of the nasal vestibulum in patients carrying methicillin-resistant Staphylococcus aureus (MRSA). However, mupirocin is also active against methicillin-sensitive S. aureus. Nasal colonization with S. aureus has been identified as a significant risk factor for surgical site infection (SSI). METHODS: Randomized trials and sequential cohort studies investigating mupirocin nasal treatment for prophylaxis of SSI in elective surgery in comparison with placebo or no treatment were found by Medline review and additional manual search. Evaluable studies were analyzed regarding the influence of mupirocin on the rate of all SSIs and, specifically, of SSIs due to S. aureus. The effect in cardiosurgical patients was analyzed in detail. RESULTS: Four randomized and seven sequential open cohort studies were analyzed. Study design and mupirocin application schemes varied considerably. Three out of 5 studies carried out in cardiac surgery patients showed a significant reduction in sternotomy site infections. However, all three studies were open sequential cohort studies. By contrast, the only prospective, randomized, double-blind study in cardiosurgical patients showed no benefit of mupirocin. In other surgical disciplines, results were inconclusive or negative. Two studies specifically addressing the prevention of SSIs due to MRSA showed a significant effect of mupirocin on postsurgical infections due to this organism. CONCLUSIONS: Because of the heterogeneity of the studies and the variability of results, no recommendation can be given for the general use of mupirocin in elective surgical patients. Specifically, because of the negative result of a recently published high-quality study, no recommendation can be made for the use of mupirocin in cardiosurgical patients. By contrast, eradication of MRSA before surgery appears to lower SSI rates due to MRSA and is therefore recommended.

[Gait analysis in limb-preserving tumour surgery--kinematic gait patterns after resection of malignant bone tumours near the knee joint]. / Ganganalyse bei extremitätenerhaltender Tumorchirurgie--Vergleich der Bewegungsmuster nach Resektion primär maligner Tumoren im Bereich des Kniegelenkes.

AIM: Limb-preserving surgery is the most common therapeutic approach in cases of malignant bone tumours near the knee joint. Although good functional results have been reported for tumours located in the distal femur, tumours in the proximal tibia have been investigated less frequently. The objective of the current study was to compare the kinematic gait patterns in patients with tumours in the femur vs. the tibia. METHOD: 11 patients with an arthroplasty after a primary malignant bone tumour were included (5 femur, 6 tibia). Their speed-specific kinematic gait patterns were quantified. 10 healthy volunteers and 6 patients with normal knee arthroplasty served as a reference group. RESULTS: The tibia patients walked significantly more slowly than the femur patients. They showed a similar overall gait pattern predominantly characterised by a hyperextended knee during stance. CONCLUSION: The differences in walking speed between the two groups of tumour patients did not transfer to different gait patterns. Limb-preserving surgery is thus a valuable therapeutic option also for patients with primary tumours in the tibia.

Efficacy of the combination of fluticasone propionate and salmeterol in patients with moderate persistent asthma within a "real-life" setting.

There are only few data on the effectiveness of recommended drug therapies in asthma under "real-life" conditions without targeted intervention. The study aimed at analyzing the efficacy of the fixed combination of the inhaled corticosteroid fluticasone propionate and the long-acting beta2-agonist salmeterol (FS) for maintenance treatment of moderate persistent asthma (GINA stage 3) within an observational design, mimicking "real-life" as closely as possible. The fixed combination was compared with other forms of treatment that were in accordance with treatment guidelines (pooled comparison (PC) group). Patients kept a diary during a 12-month observation period and routine visits were taken for surveillance. Among 596 patients, 371 patients belonged to the FS and 225 patients to the PC group. The proportion of symptom-free days (SFD) was higher in the FS than PC group (median, 76 vs 67%; p=0.002). Furthermore, the change in asthma control score (p<0.0001) and the percent increase in FEV1 (p<0.05) after 12 months were greater. There was a lower percentage of patients with hospital stays (p<0.05). The proportions of episode-free or sick-leave days and the number of routine or emergency visits did not significantly differ between groups. Direct costs of treatment per SFD were lower in the FS than PC group (median, 3.78 vs 4.41 Euro; p<0.05). We conclude that in a setup close to clinical practice treatment of patients with moderate persistent asthma with the fixed combination of fluticasone propionate and salmeterol has beneficial effects compared to other forms of therapy and can improve cost-efficiency.

A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study.

AIMS/HYPOTHESIS: The aim of this 52-week, open-label, non-inferiority trial was to compare the safety and efficacy of exenatide (an incretin mimetic) with that of biphasic insulin aspart. MATERIALS AND METHODS: Patients on metformin and a sulfonylurea were randomised to exenatide (n = 253; 5 microg twice daily for 4 weeks, 10 microg thereafter) or biphasic insulin aspart (n = 248; twice-daily doses titrated for optimal glucose control), while continuing with metformin and sulfonylurea treatment. RESULTS: Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart (mean+/-SEM, HbA(1c) change: exenatide -1.04 +/- 0.07%, biphasic insulin aspart -0.89 +/- 0.06%; difference -0.15 [95% CI -0.32 to 0.01]%). Exenatide-treated patients lost weight, while patients treated with biphasic insulin aspart gained weight [between-group difference -5.4 (95% CI -5.9 to -5.0) kg]. Both treatments reduced fasting serum glucose (exenatide -1.8 +/- 0.2 mmol/l, p < 0.001; biphasic insulin aspart -1.7 +/- 0.2 mmol/l, p < 0.001). Greater reductions in postprandial glucose excursions following morning (p < 0.001), midday (p = 0.002) and evening meals (p < 0.001) were observed with exenatide. The withdrawal rate was 21.3% (54/253) for exenatide and 10.1% (25/248) for biphasic insulin aspart. Nausea (33% incidence, 3.5% discontinuation) was the most common adverse event observed with exenatide. CONCLUSIONS/INTERPRETATION: Exenatide treatment resulted in HbA(1c) reduction similar to biphasic insulin aspart and provided better postprandial glycaemic control, making it a potential alternative for the treatment of type 2 diabetes. Treatment with biphasic insulin aspart was associated with weight gain and lower risk of adverse gastrointestinal events. Although the availability of glucose-lowering agents associated with weight reduction may be considered a therapeutic advance, the long-term implications of progressive weight reduction observed with exenatide have yet to be defined.