Diagnostic accuracy of wrist MRI in comparison to wrist arthroscopy regarding TFCC lesions in clinical practice.

INTRODUCTION: The purpose of this study was to arthroscopically verify MRI diagnostic accuracy for triangular fibrocartilage complex (TFCC) lesions in a regular clinical environment. METHODS: A total of 859 patients' data with both preoperative MRI of the wrist and additional wrist arthroscopy were retrospectively reviewed. Two board-certified hand surgeons and one orthopaedic surgeon executed wrist arthroscopy, whereas more than 100 radiologists examined the MRI of the wrist. The accordance of TFCC lesion classification using MRI in comparison to wrist arthroscopy and diagnostic precision of the former depending on technical details were evaluated. RESULTS: Diagnostic accuracy of MRI for TFCC lesions is poor in comparison to wrist arthroscopy as the reference standard. Technical specifications for MRI of the wrist are heterogeneous among the radiologists. These parameters have not improved accuracy of TFCC evaluation at large. CONCLUSION: The accuracy of MRI in a regular clinical environment still remains inferior to wrist arthroscopy for detection of TFCC lesions. Development of a standard MRI protocol may be implemented on a regular basis and application of the Palmer classification for TFCC lesion should be sought.

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.

Why does a point of care guided transfusion algorithm not improve blood loss and transfusion practice in patients undergoing high-risk cardiac surgery? A prospective randomized controlled pilot study.

BACKGROUND: Adult cardiac surgery is often complicated by elevated blood losses that account for elevated transfusion requirements. Perioperative bleeding and transfusion of blood products are major risk factors for morbidity and mortality. Timely diagnostic and goal-directed therapies aim at the reduction of bleeding and need for allogeneic transfusions. METHODS: Single-centre, prospective, randomized trial assessing blood loss and transfusion requirements of 26 adult patients undergoing elective cardiac surgery at high risk for perioperative bleeding. Primary endpoint was blood loss at 24 h postoperatively. Random assignment to intra- and postoperative haemostatic management following either an algorithm based on conventional coagulation assays (conventional group: platelet count, aPTT, PT, fibrinogen) or based on point-of-care (PoC-group) monitoring, i.e. activated rotational thromboelastometry (ROTEM®) combined with multiple aggregometry (Multiplate®). Differences between groups were analysed using nonparametric tests for independent samples. RESULTS: The study was terminated after interim analysis (n = 26). Chest tube drainage volume was 360 ml (IQR 229-599 ml) in the conventional group, and 380 ml (IQR 310-590 ml) in the PoC-group (p = 0.767) after 24 h. Basic patient characteristics, results of PoC coagulation assays, and transfusion requirements of red blood cells and fresh frozen plasma did not differ between groups. Coagulation results were comparable. Platelets were transfused in the PoC group only. CONCLUSION: Blood loss via chest tube drainage and transfusion amounts were not different comparing PoC- and central lab-driven transfusion algorithms in subjects that underwent high-risk cardiac surgery. Routine PoC coagulation diagnostics do not seem to be beneficial when actual blood loss is low. High risk procedures might not suffice as a sole risk factor for increased blood loss. TRIAL REGISTRATION: NCT01402739 , Date of registration July 26, 2011.

Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy.

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Anisotropic Exchange within Decoupled Tetrahedra in the Quantum Breathing Pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11}.

The low energy spin excitation spectrum of the breathing pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11} has been investigated with inelastic neutron scattering. Several nearly resolution limited modes with no observable dispersion are observed at 250 mK while, at elevated temperatures, transitions between excited levels become visible. To gain deeper insight, a theoretical model of isolated Yb^{3+} tetrahedra parametrized by four anisotropic exchange constants is constructed. The model reproduces the inelastic neutron scattering data, specific heat, and magnetic susceptibility with high fidelity. The fitted exchange parameters reveal a Heisenberg antiferromagnet with a very large Dzyaloshinskii-Moriya interaction. Using this model, we predict the appearance of an unusual octupolar paramagnet at low temperatures and speculate on the development of intertetrahedron correlations.

Two-Color Radiation Generated in a Seeded Free-Electron Laser with Two Electron Beams.

We present the experimental evidence of the generation of coherent and statistically stable two-color free-electron laser radiation obtained by seeding an electron beam double peaked in energy with a laser pulse single spiked in frequency. The radiation presents two neat spectral lines, with time delay, frequency separation, and relative intensity that can be accurately controlled. The analysis of the emitted radiation shows a temporal coherence and a shot-to-shot regularity in frequency significantly enhanced with respect to the self-amplified spontaneous emission.

Superradiant cascade in a seeded free-electron laser.

We report measurements demonstrating the concept of the free-electron laser (FEL) superradiant cascade. Radiation (λ(rad) = 200 nm) at the second harmonic of a short, intense seed laser pulse (λ(seed) = 400 nm) was generated by the cascaded FEL scheme at the transition between the modulator and radiator undulator sections. The superradiance of the ultrashort pulse is confirmed by detailed measurements of the resulting spectral structure, the intensity level of the produced harmonics, and the trend of the energy growth along the undulator. These results are compared to numerical particle simulations using the FEL code GENESIS 1.3 and show a satisfactory agreement.

Observation of time-domain modulation of free-electron-laser pulses by multipeaked electron-energy spectrum.

We present the experimental demonstration of a new scheme for the generation of ultrashort pulse trains based on free-electron-laser (FEL) emission from a multipeaked electron energy distribution. Two electron beamlets with energy difference larger than the FEL parameter ρ have been generated by illuminating the cathode with two ps-spaced laser pulses, followed by a rotation of the longitudinal phase space by velocity bunching in the linac. The resulting self-amplified spontaneous emission FEL radiation, measured through frequency-resolved optical gating diagnostics, reveals a double-peaked spectrum and a temporally modulated pulse structure.

A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy.

BACKGROUND: Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted. This phase II study was conducted to evaluate sunitinib, an oral antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting. MATERIAL AND METHODS: The primary end point of this randomized phase II trial was the objective response rate according to RECIST criteria and/or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies. A selection design was employed to compare two schedules of sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days off drug; and arm 2: 37.5 mg sunitinib administered daily continuously). RESULTS: Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous treatment arm (arm 1) and 37 patients were randomly allocated to the continuous treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We observed six responders (complete response + partial response) in arm 1 (16.7%) and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1: 4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed no significant difference. Adverse events included fatigue as well as cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic laboratory abnormalities. Pattern and frequency of adverse events revealed no substantial differences between both treatment groups. CONCLUSIONS: Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer. The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer.

High-order-harmonic generation and superradiance in a seeded free-electron laser.

Higher order harmonic generation in a free-electron laser amplifier operating in the superradiant regime [R. H. Dicke, Phys. Rev. 93, 99 (1954).] has been observed. Superradiance has been induced by seeding a single-pass amplifier with the second harmonic of a Ti:sapphire laser, generated in a ß-Barium borate crystal, at seed intensities comparable to the free-electron laser saturation intensity. Pulse energy and spectral distributions of the harmonics up to the 11th order have been measured and compared with simulations.

Prevalence of types of methicillin-resistant Staphylococcus aureus in turkey flocks and personnel attending the animals.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have been isolated from a number of livestock species and persons involved in animal production. We investigated the prevalence of LA-MRSA in fattening turkeys and people living on farms that house fattening turkeys. Eighteen (90%) of 20 investigated flocks were positive for MRSA, and on 12 of the farms 22 (37·3%) of 59 persons sampled were positive for MRSA. People with frequent access to the stables were more likely to be positive for MRSA. In most flocks MRSA that could be assigned to clonal complex (CC) 398 were detected. In five flocks MRSA of spa-type t002 that is not related to CC398 were identified. Moreover, other methicillin-resistant Staphylococcus spp. were detected on 11 farms and in eight people working on the farms.

The psychoeducational program for children with epilepsy and their parents (FAMOSES): results of a controlled pilot study and a survey of parent satisfaction over a five-year period.

Feasibility of the educational program FAMOSES (modular service package epilepsy for families) was evaluated in a controlled pilot study. Parents of children with epilepsy from epilepsy centers in Germany were allocated to either educational group (treatment group, n=55) or waiting-list group (control group, n=48). Questionnaires included epilepsy-specific scales (knowledge, coping, adaptation, anxiety, rules and limitations, seizure management, impact of epilepsy). Multivariate analysis of variance with repeated measurements indicated significant improvements in the treatment group compared to the control group (time×group interaction: p<0.01). Univariate analyses (ANOVA) confirmed improvements in knowledge (p<0.001), adaptation (p<0.01), epilepsy-related anxiety (p<0.05), and seizure management (p<0.05). Surveillance as well as seizure frequency (p<0.05) of children whose parents participated in the treatment group was reduced (p<0.05). Furthermore, parents' satisfaction with the content and interactive didactic format of the program was assessed in a survey with 852 parents over a five-year period. This survey showed an improvement over the course of time (p<0.05). Feasibility and need for the educational program were confirmed.

Identification of Yersinia ruckeri from diseased salmonid fish by Fourier transform infrared spectroscopy.

Yersinia ruckeri is the causative agent of enteric redmouth disease (ERM), which mainly affects salmonid fish. Isolates of Y. ruckeri from diseased salmonid fish were obtained over a 6-year period from eight fish farms in the State of Baden-Württemberg, Southwest Germany. The strains were characterized by biochemical methods and Fourier transform infrared spectroscopy (FT-IR) combined with artificial neural network analysis. These methods were complemented by 16S rDNA sequencing for several isolates. The set of strains from these fish farms included sorbitol-positive, gelatinase-positive and non-motile Y. ruckeri. These variants were differentiated with an advanced FT-IR module, which is part of a higher-ranking method including more than 200 well-defined Yersinia strains against a background of more than 1000 other Gram-negative isolates. Validation of the newly constructed method yielded 97.4% of Y. ruckeri identified correctly on the species level. Thus, the FT-IR analysis enables distinction of all Y. ruckeri from other Yersinia species (e.g. fish-borne Y. enterocolitica) and other Enterobacteriaceae typically misidentified because of similar biochemical reaction profiles, especially Hafnia alvei. The differentiation of sorbitol-positive variants of Y. ruckeri using FT-IR was demonstrated.

Self-amplified spontaneous emission free-electron laser with an energy-chirped electron beam and undulator tapering.

We report the first experimental implementation of a method based on simultaneous use of an energy chirp in the electron beam and a tapered undulator, for the generation of ultrashort pulses in a self-amplified spontaneous emission mode free-electron laser (SASE FEL). The experiment, performed at the SPARC FEL test facility, demonstrates the possibility of compensating the nominally detrimental effect of the chirp by a proper taper of the undulator gaps. An increase of more than 1 order of magnitude in the pulse energy is observed in comparison to the untapered case, accompanied by FEL spectra where the typical SASE spiking is suppressed.

High-gain harmonic-generation free-electron laser seeded by harmonics generated in gas.

The injection of a seed in a free-electron laser (FEL) amplifier reduces the saturation length and improves the longitudinal coherence. A cascaded FEL, operating in the high-gain harmonic-generation regime, allows us to extend the beneficial effects of the seed to shorter wavelengths. We report on the first operation of a high-gain harmonic-generation free-electron laser, seeded with harmonics generated in gas. The third harmonics of a Ti:sapphire laser, generated in a gas cell, has been amplified and up-converted to its second harmonic (λ(rad)=133 nm) in a FEL cascaded configuration based on a variable number of modulators and radiators. We studied the transition between coherent harmonic generation and superradiant regime, optimizing the laser performances with respect to the number of modulators and radiators.

Crystallization process of carbonate substituted hydroxyapatite nanoparticles in toothpastes upon physiological conditions: an in situ time-resolved X-ray diffraction study.

The crystallization process in recently developed toothpastes, containing nanoparticles of carbonate substituted hydroxyapatite (nano-CHA), was investigated. For this purpose, the non-conventional Energy Dispersive X-Ray Diffraction technique, that demonstrated to be a powerful tool to follow in situ phase transformations, was applied, for the first time, to products of pharmaceutical-cosmetic interest. Two types of toothpastes, containing 15 and 20 wt% of nano-CHA, respectively, have been studied. It was observed that, after mixing the toothpastes with water and saliva in order to reproduce in vivo conditions, a crystallization of nano-CHA takes place. Such process occurs in a characteristic time of (22 +/- 1) min for the toothpaste containing 15 wt% of nano-CHA and of (3.9 +/- 0.5) min for the one containing 20% of nano-CHA. For both toothpastes, a 10% increase in grain dimensions was observed over an average characteristic time of (55 +/- 5) min.

Colloidal forming of macroporous calcium pyrophosphate bioceramics in 3D-printed molds.

A technique for colloidal forming of Ca2P2O7 macroporous bioceramics, based on low-pressure injection molding (LPIM) of a glycerol-water slip containing Ca2P2O7 and Ca(Н2PO4)2 into a plastic mold fabricated via FDM 3D-printing, was proposed. Chemical reaction between the solid phases of the water containing slip - Ca2P2O7 and Ca(Н2PO4)2, resulting in brushite (CaHPO4·2H2O) formation, led to consolidation of the casting and preserved its complex architecture in the course of mold burning-out. Macroporous ceramics of Kelvin structure (70% macropores with the sizes from 2 up to 4 mm), based on a pre-defined composition with 10 wt% Ca(PO3)2 and sintered in liquid-phase regime, demonstrated a compressive strength of 1.4 ± 0.1 MPa at a density of 22 ± 2%. In vitro tests on bioactivity in SBF solution, as well as on resorption of the ceramics in model solution of citric acid, were carried out.

Biocompatibility of biphasic α,ß-tricalcium phosphate ceramics in vitro.

The biocompatibility of biphasic α,ß-tricalcium phosphate ceramics, obtained by annealing a compact preform based on ß-tricalcium phosphate powder, was studied in vitro. It was found that within 10-30 days the adhesion of primary dental pulp stem cells located on the surface of biphasic α,ß-tricalcium phosphate ceramics is suppressed. Decrease of the cell number on the surface of biphasic α,ß-tricalcium phosphate ceramics, most likely, can be associated with both the pH level (acidic) as a result of hydrolysis of the more soluble phase of α-tricalcium phosphate and with the nature of surface that changes as a result of the formation and growth of hydroxyapatite crystals.

[Simulation-based anaesthesia crisis resource management training. Results of a survey on learning success]. / Simulationsbasiertes "Anaesthesia-Crisis-Resource-Management-Training". Ergebnisse einer Nachbefragung zum Lernerfolg.

BACKGROUND: Up to as many as 38,000 people die in German hospitals each year as a result of preventable medical errors. Anesthetic procedures are generally safer than internal medical procedures and the mortality associated with anesthesia is estimated to be 3.3-5 cases per million. However, this is still 10 times higher than the risk associated with civilian aviation for example. Up to 80% of mistakes are attributable to inadequate execution of non-technical skills (NTS) such as communication, teamwork and organization of the working environment. Training in non-technical skills through Anesthesia Crisis Resource Management (ACRM) is an integral part of the Berlin Simulation Training (BeST) curriculum. The aim of this study was to describe the subjective evaluation of change in routine clinical behavior as a result of simulator training using latent outcome variables such as "subjective evaluation of learning outcome", with special emphasis on communication. MATERIAL AND METHODS: In total 235 doctors with varying levels of professional experience received BeST training between 2001 and 2004. An anonymous postal questionnaire was sent to 228 of these participants and the response rate was 64% The questionnaire contained 13 questions covering evaluation of the workshop and learning outcome with respect to communication in the operating room (OR), teamwork in the OR and medical knowledge. Following factor analysis 3 latent outcome variables (subjective evaluation of the learning outcome, workshop-related change in perception of the value of communication and general value and relevance) were generated. Logistic regression was used to determine whether there was any relationship between the latent outcome variables and a number of independent factors. RESULTS: It was not possible to demonstrate any relationship between the level of professional training, age or date of the workshop and the variables selected to describe subjective evaluation of behavioral change as a result of the workshop. How realistic the candidates perceived the training scenarios to be (p<0.01) and the sex of the candidates (p=0.03) were both significantly related to evaluation and female candidates were more likely to positively evaluate the simulator training. From the candidates' perspective the training significantly altered their perception of the value of NTSs, and in particular communication, during the management of critical incidents in the OR. CONCLUSION: Well-staged and realistic simulation is associated with better learning outcomes. It may be important to take gender aspects into account in ACRM training.