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Background Biomechanical studies have shown a higher compressive force and higher torsional stiffness for fixation with three screws compared to two screws. However, clinical data to compare these fixation techniques is still lacking. Methods A retrospective analysis of 113 patients was performed, who underwent isolated subtalar fusion between January 2006 and April 2018. Results Revision arthrodesis was required in 8% (n = 6/36) for 3-screw-fixation and 38% (n = 35/77) for 2-screw-fixation. For 3-screw-fixation, non-union, was observed in 14% (n = 5/36) compared to 35% (n = 27/77) in 2-screw fixation. Non-union (p = .025) and revision arthrodesis (p = .034) were significantly more frequent in patients with 2 screws. A body mass index ≥30 kg/m2 (p = .04, OR = 2.6,95%CI:1.1–6.3), prior ankle-fusion (p = .017,OR = 4.4,95%CI:1.3–14.5) and diabetes mellitus (p = .04,OR = 4.9,95%CI:1.1–17.8) were associated with a higher rate of revision arthrodesis. Conclusions Our findings suggest that successful subtalar fusion is more reliably achieved with use of three screws. However, future prospective studies will be necessary to further specify this recommendation.

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 − 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.

Collisional damping quadrupole ion guides have become popular tools in mass spectrometry. In such devices, ions are cooled by collisions with a buffer gas and focused to trajectories near the axis of the ion guide under the influence of a radio frequency (RF) field. This produces a narrow beam of low-energy ions which can be transported with high efficiency. Typically, quadrupole ion guides are constructed of four parallel rods to which RF voltages are applied. To overcome the dampening of the axial velocity component resulting from collisions with neutral gas particles, an additional static axial field is provided by dividing the rods in several segments and applying an electric potential to each segment. However, this method is mechanically complex, requiring a precise alignment of all segments, and several separate connections for the DC und RF voltages to all segments. In this work, we present a simple and low-cost segmented quadrupole ion guide design that is based on standard printed circuit boards (PCB) including both the segmented electrodes as well as the signal distribution network. Furthermore, we present simulations of the ion movement inside this PCB quadrupole and experimentally evaluate the ion transfer. Our measurements show that the segmented PCB quadrupole with planar electrodes reaches similar ion transmissions in comparison with conventional quadrupole ion guides built from segmented circular rods.

Although birds are hosts to a large number of microorganisms, microbes have rarely been found in avian oil glands. Here, we report on two strains of a new bacterial species from the preen oil of American barn owls (Tyto furcata). Phenotypic as well as genotypic methods placed the isolates to the genus Kocuria. Strains are non-fastidious, non-lipophilic Gram-positive cocci and can be unambiguously discriminated from their closest relative Kocuria rhizophila DSM 11926T. In phylogenetic trees, the owl bacteria formed a distinct cluster which was clearly separated from all other known Kocuria species. The same conclusion was drawn from MALDI-TOF MS analyses. Once again, the new bacterial strains were very similar to one another, but exhibited substantial differences when compared to the most closely related species. Besides, the results of the biochemical tests, optimum growth conditions and pigmentation differed from closely related Kocuria spp. Finally, ANIb values of less than 87% provided striking evidence that the isolates recovered from American barn owls represent a hitherto undescribed species, for which we propose the name Kocuria tytonicola sp. nov. The type strain is 489T (DSM 104133T = LMG 29945T, taxonumber TA00340).

The generation of artificial human tissue by 3D-bioprinting has expanded significantly as a clinically relevant research topic in recent years. However, to produce a complex and viable tissue, in-depth biological understanding and advanced printing techniques are required with a high number of process parameters. Here, we systematically evaluate the process parameters relevant for a hybrid bioprinting process based on fused-deposition modeling (FDM) of thermoplastic material and microextrusion of a cell-laden hydrogel. First, we investigated the effect of the printing temperature of polycaprolactone (PCL), on the junction strength between individual fused filaments and on the viability of immortalized mesenchymal stem cells (iMSC) in the surrounding alginate-gelatin-hydrogel. It was found that a printing temperature of 140 °C and bonds with an angle of 90° between the filaments provided a good compromise between bonding strength of the filaments and the viability of the surrounding cells. Using these process parameters obtained from individual fused filaments, we then printed cubic test structures with a volume of 10 × 10 × 10 mm

Here we report the first High Kinetic Energy-Ion Mobility Spectrometry-Mass Spectrometric (HiKE-IMSMS) investigations involving four fluranes; isoflurane, enflurane, sevoflurane and desflurane. Unlike standard (atmospheric pressure) IMS, HiKEIMS can detect these compounds in positive ion mode. This is because its low-pressure environment (similar to 14 mbar) and the associated short ion drift times in the HiKEIMS ensure the reagent ions O-2+(center dot) and H3O+ are present in the reaction region, and these can react with the fluranes by dissociative charge and proton transfer, respectively. However, their ion intensities are very dependent on the value of the reduced electric field (E/N) applied and the humidity of the air in the reaction region of the HiKE-IMS. In this paper we explore the potential use of HiKE-IMS for air quality control and breath analysis of fluranes. To help in the interpretation of the ion mobility spectra, and hence the ion-flurane chemistry occurring in reaction region, a HiKE-IMS was coupled to a Time-of-Flight Mass Spectrometer so that the m/z values of both the reagent and product ions that are contained within the various ion mobility peaks observed could be identified with a high level of confidence. The dependencies of the intensities of these ions as functions of E/N (30-115 Td) and humidity in the reaction region are reported. A number of product ions have been observed only under low humidity conditions (H2O volume-mixing ratio 100 ppm(v)), including CHF(2+)and CHFCl (+) for isoflurane and enflurane, CHF2(+), CF3(+) and C3H2F5O+ for desflurane, and CH3O+, CHF2+, C3H3F4O+, C4H3F6O+ and C4H3F6O+(H2O) for sevoflurane. It is interesting to note that CH3O+, CHF2+, CHFCl+ and CF3+ have shorter drift times than that measured for O-2(+center dot) This is explained by resonant charge transfer reaction processes occurring in the drift region: O-2(+center dot) + O-2 ? O-2+(center dot).O O-2 + O-2 +(center dot) (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Safeguarding water quality is resource-intensive and costly. Especially in cases of accidents or disasters, compact devices that allow quick assessment of the current situation are lacking. The objective of this work is the development of a portable measuring device for on-site detection of pollutants in water based on nano-high performance liquid chromatography (nano-HPLC) and electrospray ionization (ESI) ion mobility spectrometry (IMS). Integrated online enrichment by means of solid phase extraction (SPE) further improves sensitivity. In this work, an SPE cartridge exchange unit is presented, which was developed by additive manufacturing in a cost-effective and resource-efficient way. Prerequisites are an easy adaptation to commercially available SPE cartridges and pressure stability of up to 50 bar. In addition, a compact ESI-IMS with 75 mm drift tube length and a resolving power of R = 100 is presented that enables ionization, separation based on ion mobility and detection of analytes at a flow rate of 0.6 – 1.8 µL/min from the liquid phase. This approach also allows miniaturization of the overall system leading to a reduction in energy requirements and the amount of solvents used. For future environmentally benign systems, complete elimination of toxic solvents would be ideal. Therefore, acetonitrile and the nontoxic ethanol are compared as organic mobile phase in terms of elution and ionization efficiency. For characterization, a test mixture containing relevant target analytes, such as chlortoluron, isoproturon, pyrimethanil, mepanipyrim, cyprodinil and carbamazepine, is analyzed. In addition, the analytical greenness metric approach tool is used to evaluate the overall system in terms of its green credentials. It was shown that ethanol can be well used as an organic solvent for the mobile phase and even exhibits better ionization than acetonitrile for the selected model analytes. Furthermore, a relatively high orthogonality of O=0.53 and an effective 2D peak capacity of ²Dnₑff=174 are reached. Due to the overall miniaturization and splitless coupling, the aims of green chemistry can be met, and ideally a value of 0.92 can be achieved using the AGREE tool for the presented system. CA extern

As evolutionarily optimised defence compounds, antimicrobial peptides (AMPs) represent a powerful tool against bacterial infections. Ranalexin, an AMP found in the skin of the American bullfrog (Rana catesbeiana), is primarily active against Gram-positive bacteria, with minimum inhibitory concentrations (MICs) of 8-16 mg/L, but shows weaker activity against Gram-negative bacteria (MICs > 64 mg/L). By substitution of six N-terminal amino acids by saturated fatty acids [decanoic acid (C10:0) to myristic acid (C14:0)], lipopeptide derivatives with enhanced antimicrobial activity were developed. The antimicrobial capacity of the peptides was tested against different bacterial strains, including multiresistant clinical isolates. C13C3lexin, the most potent derivative, showed MICs of 2-8 mg/L against Gram-positive bacteria and 2-16 mg/L against Gram-negative bacteria. In time-kill studies, it was clearly shown that ranalexin and the lipopeptide C13C3lexin function as concentration-dependent, fast-acting substances against different bacteria. Cell viability assays revealed that cytotoxicity towards human cells increases with the chain length of the attached fatty acid (IC50, 12.74-108.10 µg/mL). Furthermore, using positron emission tomography (PET) imaging, pharmacokinetic studies of 68Ga-labelled ranalexin and its derivatives were performed for the first time. Here it was demonstrated that ranalexin is rapidly cleared via the kidneys within 1 h post-injection. In contrast, the lipopeptide showed greatly extended circulation in the bloodstream and a shift from renal to hepatic accumulation characteristics. Therefore, the more favourable pharmacokinetics and enhanced antimicrobial activity clearly demonstrate the potential of the lipopeptide AMPs as novel ammunition against emerging multiresistant bacterial pathogens.

To ensure high quality output of biotechnological processes, relevant process parameters need to be monitored. As bioprocesses are increasingly executed in single use bioreactors, there is an increasing demand for new sensors applicable to these processes. In this work, we investigate different approaches for continuous non-invasive cell growth monitoring, especially for single use bioreactor applications. Therefore, the permittivity of the cell culture is used as a measure for the biomass. In a first step, a measuring procedure based on the transmission measurement of an electromagnetic wave is investigated. It appears that the penetration depth of this sensor is not sufficient for a noninvasive measurement through the polymer wall of a single use bioreactor. Therefore, alternative setups based on magnetic induction are investigated. The initial setup is very simple. It consists of a planar coil connected to an impedance analyzer. The coil is attached to the outside of the polymer foil of the single use bioreactor and an impedance spectrum is measured. To evaluate the sensor, E. coli cultivations are performed in a modified cultivation setup, which enables measurements through the polymer foil of a Sartorius BIOSTAT® CultiBag RM, and additionally allows sampling of culture medium for optical density reference measurements. The resonance peak of the coil in the impedance spectrum, is observed as measure for the optical density. Regardless of the simple sensor construction, we found a good correlation between optical density and the damping ratio of the resonance peak. However, the sensor signal shows saturation towards high optical densities. Therefore, an LTCC coil producing a higher magnetic flux density in the culture medium is investigated subsequently. This sensor shows a linear response up to high optical densities, but the sensitivity is reduced compared to the former used coil and therefore scattering of the data is increased. However, to increase the sensitivity, a linear variable differential transformer is realized. Using this setup, the influence of the primary magnetic flux is eliminated from the measuring voltage. This approach delivers the most promising results, as the sensor response is linear up to high optical densities and data scattering is low.

In a former work on the investigation of ion generation and ion-ion recombination kinetics at atmospheric pressure with an ion mobility spectrometer equipped with a pulsable electron emitter, we found that different ion species and concentrations could be distinguished by only considering the specific ion-ion recombination kinetics. In the present work, these findings are utilized for the development of a novel compact and simple gas sensor. In a first step, the gas mixture becomes ionized by atmospheric pressure chemical ionization for a defined ionization time. Subsequently the ionization source is turned off and the ion specific decay of the ion concentration as a function of the recombination time is measured. This decay depends on the generated ion species and the compounds of the gas mixture respectively. For the analysis of these decay curves and visualization of the results, we use discriminant analysis. As an exemplary target analyte, we chose dimethyl-methylphosphonate (DMMP). With the current setup we achieve a limit of detection of 8 ppbv for the detection of DMMP in presence of significant higher ammonia and formaldehyde concentrations by only considering the recombination kinetics.

Purpose Accuracy and feasibility of corrective osteotomies using 3-dimensional planning tools and patient-specific instrumentation has been reported by multiple authors with promising results. However, studies describing clinical outcomes following these procedures are rare. Therefore, the purpose of this study was to compare the results of computer-assisted corrective osteotomies of the diaphyseal and distal radius with a conventional non–computer-assisted technique regarding duration of surgery, consolidation of the osteotomy, and complications. Also, subjective and objective clinical outcome parameters were assessed. Methods We retrospectively compared the results of 31 patients who underwent a corrective osteotomy performed conventionally with 25 patients treated with a computer-assisted method (CA) using patient-specific instrumentation. Baseline data were similar among both groups. The duration of surgery, bony consolidation, complications, gain in range of motion, and subjective outcome were recorded. Results The mean operating time was significantly shorter in the CA group compared with the conventional group. After 12 weeks, significantly more osteotomies were considered healed in the CA group compared with the conventional group. Two patients in the CA group required revision surgery to treat nonunion of the osteotomy. Otherwise clinical results were similar among both groups. Conclusions The results demonstrate that the computer-assisted method facilitates shorter operation times while providing similar clinical results. Type of study/level of evidence Therapeutic IV.

In this work, we present a novel concept for a gas chromatography detector utilizing an atmospheric pressure chemical ionization which is initialized by a dielectric barrier discharge. In general, such a detector can be simple and low-cost, while achieving extremely good limits of detection. However, it is non-selective apart from the use of chemical dopants. Here, a demonstrator manufactured entirely from fused silica capillaries and printed circuit boards is shown. It has a size of 75 × 60 × 25 mm 3 and utilizes only 2W of power in total. Unlike other known discharge detectors, which require high-purity helium, this detector can theoretically be operated using any gas able to form stable ion species. Here, purified air is used. With this setup, limits of detection in the low parts-per-billion range have been obtained for acetone.

Streptococcus pneumoniae is a rare cause of urinary tract infection. Between January 2010 and December 2014, 26 urine samples from 18 different patients contained S. pneumoniae at the Department for Infectious Diseases, University Hospital of Heidelberg. Patient age varied between three and 72 years. 13 patients were male and five were female. Past medical histories of 16 patients were available. Eight patients had a past medical history of renal transplant and four patients had other renal dysfunctions. Further analyses of the isolates revealed that the aspect of colonies is more resembling S. mitis than invasive isolates of S. pneumoniae. Optochin disk diameters tend to be 14 mm or smaller. Identification using MALDI-TOF or VITEK2 identification cards was accurate. Only 2 isolates showed a decreased susceptibility towards penicillin (MIC = 0.5 mg/L). Eight different serotypes were identified using a PCR approach as well Neufeld-Quellungs reaction.

Objectives Although regular physical exercise clearly reduces cardiovascular morbidity risk, long-term endurance sports practice has been recognized as a risk factor for atrial fibrillation (AF). However, the mechanisms how endurance sports can lead to AF are not yet clear. The aim of our present study was to investigate the influence of long-term endurance training on vagal tone, atrial size, and inflammatory profile in professional elite soccer players. Methods A total of 25 professional major league soccer players (mean age 24 ± 4 years) and 20 sedentary controls (mean age 26 ± 3 years) were included in the study and consecutively examined. All subjects underwent a sports cardiology check-up with physical examination, electrocardiography, echocardiography, exercise testing on a bicycle ergometer, and laboratory analysis [standard laboratory and cytokine profile: interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-8, IL-10]. Results Athletes were divided into two groups according to presence or absence of an early repolarization (ER) pattern, defined as a ST-segment elevation at the J-point (STE) ≥0.1 mm in 2 leads. Athletes with an ER pattern showed significantly lower heart rate and an increased E/e′ ratio compared to athletes without an ER pattern. STE significantly correlated with E/e′ ratio as well as with left atrial (LA) volume. The pro-inflammatory cytokines IL-6, IL-8, TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in all soccer players. However, athletes with an ER pattern had significantly higher IL-6 plasma levels than athletes without ER pattern. Furthermore, athletes with “high” level IL-6 had significantly larger LA volumes than players with “low” level IL-6. Conclusions Athletes with an ER pattern had significantly higher E/e′ ratios, reflecting higher atrial filling pressures, higher LA volume, and higher IL-6 plasma levels. All these factors may contribute to atrial remodeling over time and thus increase the risk of AF in long-term endurance sports.

Electrospray is a commonly used ionization method for the analysis of liquids. An electrospray is a dispersed nebular of charged droplets produced under the influence of a strong electrical field. Subsequently, ions are produced in a complex process initiated by evaporation of neutral solvent molecules from these droplets. We coupled an electrospray ionization source to our previously described high resolution ion mobility spectrometer with 75 mm drift tube length and a drift voltage of 5 kV. When using a tritium source for chemical gas phase ionization, a resolving power of R=100 was reported for this setup. We replaced the tritium source and the field switching shutter by an electrospray needle, a desolvation region with variable length and a three-grid shutter for injecting ions into the drift region. Preliminary measurements with tetraalkylammonium halides show that the current configuration with the electrospray ionization source maintains the resolving power of R=100. In this work, we present the characterization of our setup. One major advantage of our setup is that the desolvation region can be heated separately from the drift region so that the temperature in the drift region stays at room temperature even up to desolvation region temperatures of 100 °C. We perform parametric studies for the investigation of the influence of temperature on solvent evaporation with different ratios of water and methanol in the solvent for different analyte substances. Furthermore, the setup is operated in negative mode and spectra of bentazon with different solvents are presented.

A novel species of fastidious, lipophilic, club-shaped, Gram-positive bacteria was recovered from the preen glands of healthy Turkeys (Meleagris gallopavo) from two different locations. Phylogenetic analysis of the 16S rRNA gene showed highest similarity to Corynebacterium spheniscorum DSM 44757T (96.8%) with a 3.2 kb stretch of rpoB sharing 82.4% sequence similarity to the same species. DNA fingerprinting by ERIC-PCR and polar lipid profiles clearly differentiated the Turkey isolates from the most closely related Corynebacteria, as did MALDI-TOF MS analysis. Chemotaxonomic tests revealed the presence of corynemycolic acids with C16:0, C18:0, C18:1ω9c and tuberculostearic acid as the major cellular fatty acids. The G+C content of the type strain was 60.7 mol%. The species was susceptible to ampicillin, kanamycin A, streptomycin, amikacin, polymyxin B and vancomycin. From our results, it becomes evident that the isolated organisms represent a new species, for which the name Corynebacterium uropygiale sp. nov. is proposed. The type strain is Iso10T (=DSM 46817T = LMG 28616T).

To ensure high quality output of biotechnological processes, relevant process parameters need to be monitored. As bioprocesses are increasingly executed in single use bioreactors, there is an increasing demand for new sensors applicable to these processes. In this work, we present a low-cost sensor system for continuous non-invasive cell growth monitoring, especially for single use bioreactor applications. The system consists of a planar coil connected to a low cost network analyzer. The coil is attached to the outside of the polymer foil of the single use bioreactor and an impedance spectrum is measured. To evaluate the sensor, E. coli cultivations are performed in a modified cultivation setup, which enables measurements through the polymer foil of a Sartorius BIOSTAT ® CultiBag RM, and additionally allows sampling of culture medium for optical density reference measurements. The resonance peak of the coil in the impedance spectrum, is observed as measure for the optical density. Regardless of the simple sensor construction, we found a good correlation between optical density and the damping ratio of the resonance peak.

Over the last decade, bioprinting of artificial tissues has been developed into a significant field of research. With an increasing number of printing technologies and bioinks used in bioprinting, its complexity increases as both the printing technology and the properties of the bioink influence the cell biological functionality and printing accuracy of the printed tissue. Therefore, optimization of bioprinting processes often remains a challenge, which could be solved by a smart fine-tuning of the process parameters. We present a novel method to adjust the printing window for extrusion-based bioprinting on the basis of a two-step assessment to determine process parameters such as nozzle size, extrusion flow rate, and printing temperature. First, a suitable printing temperature is deduced from the bioink properties and second nozzle size and extrusion flow rate is selected in a way that the immediate cell damage after printing is reduced. For both steps only basic rheological properties of the bioinks need to be known as well as detailed knowledge of the cell survival in the bioink for different shear stresses. This method is applied to an exemplary alginate-gelatin hydrogel to show how the printing temperature affects the achievable printing accuracy. For this bioink, viability of immortalized mesenchymal stem cells (iMSC) decreases with about 4% per thousand Pascal increase in maximum shear stress. For different combinations of flow rate, nozzle size and nozzle shape it is shown, that only the maximum shear stress experienced by the iMSCs influences average cell viability. Factors like flow rate, nozzle size and shape only play an indirect role by influencing the maximum shear stress and individually have no significant influence on cell viability. The experimental results allow a direct adjustment of printing parameters for the presented combination of hydrogel and cell type but are not limited to it. For other bioinks, the described generic method can be easily used to systematically adjust the printing parameters. For this purpose, only the basic rheological properties and the influence of shear stress on cell survival need to be known and process parameters can be set concerning the respective application.

Ectomycorrhizal (EcM) fungi are essential for the establishment of woody perennial plants in the European Alps. From continental to local scales, environmental conditions and plant host characteristics can predict EcM community structure and composition. However, it is unclear whether EcM communities of congeneric host species and their hybrids are differentially structured at local scales. We aimed to i) characterize EcM communities of Salix helvetica, Salix purpurea and their hybrids and ii) elucidate the abiotic and biotic factors affecting EcM communities in hybrid zones. We analysed the EcM communities associated with willows in a glacier valley by combining molecular identification of fungi from individual ectomycorrhizas and from soil. We detected diverse EcM fungi forming non-modular and unnested networks, but we did not find significant differences in the overall EcM fungal community richness or composition among parental species and hybrids. Nevertheless, individual fungi differed regarding host preference. Our results demonstrate that in a sub-alpine hybrid zone with heterogeneous geomorphology, host genotype was not a strong predictor of overall EcM fungal community, but it influenced the occurrence of particular fungi.

Purpose To evaluate 3D-printed anatomic models of the distal femur and patella for diagnosis and classification of patellofemoral dysplasia in comparison to conventional radiographs (CR) and CT. Method Following local ethics committee approval, CT-datasets of 50 patients were segmented and 3D-anatomic models of the distal femur and patella were printed. An expert panel reviewed CR, CT, 3D-models and patient history and classified the femoral trochleas into normal or Dejour type A–D and the patellas into Wiberg type A–C, which served as the standard of reference. The same classifications were performed by two readers independently, first based on 3D-models and after 3 weeks based on CR and CT. Descriptive statistics, ROC-analysis and inter-reader reliability were performed. Results Trochlear dysplasia was present in 28/50 patients. Evaluations of 3D-models vs. CR/CT for trochlear dysplasia showed a sensitivity/specificity of 89.3 %/100 % vs. 96.4 %/68.2 % for reader 1 and 96.4 %/100 % vs. 96.4 %/90.9 % for reader 2, and an area under the curve of 0.946 vs. 0.823 for reader 1 (p = 0.029) and 0.982 vs. 0.937 for reader 2 (p = 0.147). Evaluations of 3D-models vs. CR/CT for the Dejour classification showed a sensitivity/specificity of 32.1 %/100 % vs. 57.1 %/68.2 % for reader 1 and 46.4 %/100 % vs. 50 %/90.9 % for reader 2 without significant differences. No significant differences existed for Wiberg-classification (50–66 % exact matches) or inter-reader reliabilities between 3D-models and CR/CT for all assessments (Kappa 0.428–0.92). Conclusion In comparison to radiographs and CT, 3D-models achieve similar diagnostic accuracy for detection of patellofemoral dysplasia and have the potential to improve diagnosis for less experienced physicians.

Background Twitter is a microblogging service providing a platform for social networking. For medical information, Twitter is an interesting channel for sharing and spreading information and as an engagement platform for different stakeholders. Benefits and caveats of uncontrolled medical information must be carefully pondered, considering the possible intended and unintended adverse outcomes of uncontrolled influencing. The aim of this study was to describe the non-commercial content shared on Twitter and to analyse the level of influence of commercial tweeters during the European Society of Medical Oncology (ESMO) 2018 annual meeting held in Munich. Design/methodology A retrospective analysis of the tweets shared in the period 19–23 October 2018 indexed with the hashtag #ESMO18 or #ESMO2018 was performed; methodology of systematic reviews was mirrored. Commercial tweeters (pharmaceutical and biotechnology companies, device manufacturers and spam tweeters) were excluded from the primary analysis, and only non-commercial tweets from and about the congress were included. Tweets were analysed using a network analytical tool (NodeXL). Results A total of 7100 tweets posted by 1334 tweeters were identified for the period of interest. Less than 10% of tweeters were identified as commercial, posting 15.7% of tweets and receiving almost one-quarter of retweets. However, pharmaceutical and biotech tweeters were substantially less likely to be mentioned by other tweeters. All of the top 10 retweeters of non-commercial content were clinicians and/or professional organisations, in stark contrast with the commercial content. Conclusions The use of social networks in medical meetings, including oncology, is increasing for real-time communication and informed opinion-making. The uncontrolled spread of information on Twitter can both stimulate discussions on non-official and non-canonical channels of communication and provide uncontrolled influencing of diverse stakeholders. The disclosure of financial declarations of interest on Twitter could enhance the transparency of the information, as is already happening in medical journals.

Background Olaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment of PSR OC. MEDIOLA assessed olaparib in combination with the anti-programmed cell death ligand1 antibody, durvalumab, in germline BRCA1 and/or BRCA2 mutated (gBRCAm) PSR OC (NCT02734004). The 12-week (wk) disease control rate (DCR) = complete response [CR] + partial response + stable disease) was presented at SGO 2018 (late-breaker abst. 4). Methods Pts had PSR OC, gBRCA1 or gBRCA2 mutation, and had received at least one prior line of platinum. Pts received olaparib 300mg PO BID for a 4-wk runin, then olaparib 300mg PO BID and durvalumab 1.5g IV q 4 wks until progressive disease. Tumours were assessed by RECIST 1.1 at baseline, 4 wks, then every 8 wks. Primary endpoints were 12wk DCR and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and biomarker analyses. Results Thirty-two/thirty-four pts treated were eligible. With the data cut-off on 1 Nov 2018, 28% pts were still on treatment. Most common ≥Grade 3 AEs were anaemia (17.6%), elevated lipase (11.8%), neutropenia (8.8%), and lymphopenia (8.8%). Five pts discontinued olaparib and three discontinued durvalumab due to an adverse event. The 28-wk DCR was 65.6% (90% CI: 49.6%, 79.4%). ORR was 71.9% (95% CI: 53.25%, 86.25%) with a total of seven CRs. Median PFS was 11.1 months (95% CI: 8.2, 15.9) with a median DoR of 10.2 months (25/75th percentile: 5.6, NC). Second-line pts (N=13, 40.6%) had not yet reached the medians for PFS or DoR. Median OS for all pts was not yet reached, with 87.0% of pts alive at 24 months (median follow up=20.4 months). Updated results will be presented. Conclusions The combination of olaparib and durvalumab was well tolerated and showed promising median PFS and DoR. Median PFS and DoR for pts with fewer prior lines of chemotherapy was not yet reached, suggesting that these pts may derive a greater benefit from the combination. The CR rate was higher than anticipated. This cohort has been expanded to further explore the durability of this chemotherapy-sparing combination. Clinical trial identification NCT02734004. Editorial acknowledgement Emma Robinson, Mudskipper Business, Ltd, funded by AstraZeneca. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure Y. Drew: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Tesaro ; Advisory / Consultancy: Genmab; Research grant / Funding (institution): Oncology; Research grant / Funding (institution): Veratsem. B. Kaufman: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Medison. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. P. Roxburgh: Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro. R.H. Alvarez: Honoraria (self): Eisai; Honoraria (self): Puma; Leadership role: Cancer Treatment Center of America. S. Domchek: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): PharmaMar. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Rocher Ros: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. K. Meyer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

As part of every standard forensic autopsy, the examination of the brain includes assessment with respect to possible edema. The quantification of edema is helpful to make a sound diagnosis in presence of multiple affections and multiple possible causes of death. The water content in certain brain regions is furthermore a promising marker to distinguish between causes of death with no visible evidence, such as suffocation, shaking impact syndrome and sudden infant death syndrome. However, in todays’ forensic medicine, no technique is available for the objective and exact quantification of edema. Therefore, the aim of this work is to develop a fast and easy-to-use measuring system for the accurate determination of the water content in human brain tissue that fits into the procedure of a routine autopsy. For our setups, the dependency between relative permittivity and water content is utilized. In former works, we presented measurements of human brain tissue using a coaxial measuring chamber and an open-ended coaxial probe. However, some drawbacks of the used methods emerged. Thus, a novel probe design using a coplanar transmission line has been developed, addressing the drawbacks of the formerly used methods. This new probe is easy to calibrate and allows fast and accurate sequential scanning for edema in human brain tissue.

Objectives The intention this PEPCAD-DES (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter) study update was to demonstrate the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in patients with DES-ISR at 3 years. Background In the PEPCAD-DES trial late lumen loss and the need for repeat target lesion revascularization (TLR) was significantly reduced with PCB angioplasty compared with plain old balloon angioplasty (POBA) in patients with drug-eluting stent in-stent restenosis (DES-ISR) at 6 months. We evaluated whether the clinical benefit of reduced TLR and major adverse cardiac events (MACE) was maintained up to 3 years. Methods A total of 110 patients with DES-ISR in native coronary arteries with reference diameters ranging from 2.5 mm to 3.5 mm and lesion lengths ≤22 mm were randomized to treatment with either PCB or POBA in a multicenter, randomized, single-blind clinical study. With a 2:1 randomization, 72 patients were randomized to the PCB group and 38 patients to the POBA group. At baseline, there were lesions with at least 2 stent layers in PCB (52.8%, 38 of 72) and POBA (55.3%, 21 of 38) patients. Results At 36 months, the TLR rates were significantly lower in the PCB group compared with the POBA control group (19.4% vs. 36.8%; p = 0.046). Multiple TLRs in individual patients were more frequent in the POBA group compared with the PCB group (more than 1 TLR: POBA, 13.2%; PCB, 1.4%; p = 0.021). The 36-month MACE rate was significantly reduced in the PCB group compared with the POBA group (20.8% vs. 52.6%, log-rank p = 0.001). Conclusions PCB angioplasty was superior to POBA for the treatment of DES-ISR patients in terms of MACE and TLR for up to 36 months. There was no late catch-up phenomenon. (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter [PEPCAD-DES]; NCT00998439 )

The goal of this study was to investigate the antimicrobial activity of bee venom and its main component, melittin, alone or in two-drug and three-drug combinations with antibiotics (vancomycin, oxacillin, and amikacin) or antimicrobial plant secondary metabolites (carvacrol, benzyl isothiocyanate, the alkaloids sanguinarine and berberine) against drug-sensitive and antibiotic-resistant microbial pathogens. The secondary metabolites were selected corresponding to the molecular targets to which they are directed, being different from those of melittin and the antibiotics. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were evaluated by the standard broth microdilution method, while synergistic or additive interactions were assessed by checkerboard dilution and time-kill curve assays. Bee venom and melittin exhibited a broad spectrum of antibacterial activity against 51 strains of both Gram-positive and Gram-negative bacteria with strong anti-MRSA and anti-VRE activity (MIC values between 6 and 800 µg/ml). Moreover, bee venom and melittin showed significant antifungal activity (MIC values between 30 and 100 µg/ml). Carvacrol displayed bactericidal activity, while BITC exhibited bacteriostatic activity against all MRSA and VRE strains tested (reference strains and clinical isolates), both compounds showed a remarkable fungicidal activity with minimum fungicidal concentration (MFC) values between 30 and 200 µg/ml. The DNA intercalating alkaloid sanguinarine showed bactericidal activity against MRSA NCTC 10442 (MBC 20 µg/ml), while berberine exhibited bacteriostatic activity against MRSA NCTC 10442 (MIC 40 µg/ml). Checkerboard dilution tests mostly revealed synergism of two-drug combinations against all the tested microorganisms with FIC indexes between 0.24 and 0.50, except for rapidly growing mycobacteria in which combinations exerted an additive effect (FICI = 0.75–1). In time-kill assays all three-drug combinations exhibited a powerful bactericidal synergistic effect against MRSA NCTC 10442, VRE ATCC 51299, and E. coli ATCC 25922 with a reduction of more than 3log10 in the colony count after 24 h. Our findings suggest that bee venom and melittin synergistically enhanced the bactericidal effect of several antimicrobial agents when applied in combination especially when the drugs affect several and differing molecular targets. These results could lead to the development of novel or complementary antibacterial drugs against MDR pathogens.

We compared a multiplex PCR diagnostic approach against specific PCR diagnosis for detection of Mycoplasma pneumoniae infection. Seventy-five percent of all M. pneumoniae infections were only detected “unintentionally” by the use of the multiplex PCR indicating underdiagnosing of M. pneumoniae due to absence of clinical suspicion., Highlights • A respiratory multiplex PCR diagnostic approach was compared against specific PCR request. • Seventy-five percent of all Mycoplasma pneumoniae infections were detected “unintentionally” with the multiplex PCR. • The data indicate underdiagnosing of M. pneumoniae due to absence of clinical suspicion.

Ion mobility spectrometry (IMS) is a well-known technique for fast trace gases detection. Employing atmospheric pressure chemical ionization in IMS, ion clusters, e.g. protonated monomer or proton bound dimer analyte ions such as MH + (H 2 O) n or M 2 H + (H 2 O) n form in the positive mode, where the chemical ionization is based on positively charged reactant ions H + (H 2 O) n . In the negative mode, where the ionization is based on negatively charged reactant ions O 2 - (H 2 O) n , similar cluster formation is possible but less common. In this paper, we investigate 2-chlorophenol, formic acid and toluene-diisocyanate as single substances and in mixtures, showing their different behavior regarding the formation of symmetric and asymmetric clusters and thus the presence and absence of additional peaks in the ion mobility spectra. Quantum-chemical calculations regarding the stabilization energy can explain the absence of certain cluster signals quite well when based on the assumption of ionization by electron capture in contrast to the typically expected ionization by proton abstraction.

The major task in most autopsies is the evaluation of circumstances and cause of a person's death. The quantification of edema, primarily in certain brain regions, is a promising marker to distinguish between certain causes of death. This is especially important if there is no visible reason, for example, in the case of distinguishing Sudden Infant Death Syndrome from Shaken Impact Syndrome. However, until now there is no standardized procedure in forensic medicine for the quantification of edema in parenchymatous organs. Therefore, the aim of our work is to develop a fast low-cost measuring system that fits into the procedure of an autopsy. One approach for an exact quantification of edema is to determine the humidity content in the tissue with the so-called oven dry method, which we used as a reference. The approach presented here is the determination of the humidity content via a measurement of the relative permittivity of the tissue. We use two different setups: a transmission and a reflection measurement. Thereby a linear regression between the humidity content and the relative permittivity was found with excellent regression coefficients of R = 0.98 for the transmission measurement and R = 0.97 for the reflection measurement. We compare the results of the used methods regarding accuracy and measuring time.

Lung cancer is characterized by the highest incidence of solid tumor-related brain metastases, which are reported with a growing incidence during the last decade. Prognostic assessment may help to identify subgroups of patients that could benefit from more aggressive therapy of metastatic disease, in particular when central nervous system is involved. The recent sub-classification of non-small cell lung cancer (NSCLC) into molecularly-defined “oncogene-addicted” tumors, the emergence of effective targeted treatments in molecularly defined patient subsets, global improvement of advanced NSCLC survival as well as the availability of refined new radiotherapy techniques are likely to impact on outcomes of patients with brain dissemination. The present review focuses on key evidence and research strategies for systemic treatment of patients with central nervous system involvement in non-small cell lung cancer.

Combinations of two or more drugs, which affect different targets, have frequently been used as a new approach against resistant bacteria. In our work we studied the antimicrobial activity (MIC, MBC) of individual drugs (the phenolic monoterpene thymol, EDTA and vancomycin), of two-drug interactions between thymol and EDTA in comparison with three-drug interactions with vancomycin against sensitive and resistant bacteria. Thymol demonstrated moderate bactericidal activity (MBC between 60 and 4000μg/ml) while EDTA only exhibited bacteriostatic activity over a range of 60-4000μg/ml. MICs of vancomycin were between 0.125 and 16μg/ml against Gram-positive and between 32 and 128μg/ml against Gram-negative bacteria. Checkerboard dilution and time-kill curve assays were performed to evaluate the mode of interaction of several combinations against Methicillin-resistant Staphylococcus aureus (MRSA NCTC 10442) and Escherichia coli (ATCC 25922). Checkerboard data indicate indifferent interaction against Gram-positive (FICI=1-1.3) and synergy against Gram-negative bacteria (FICI≈0.4), while time kill analyses suggest synergistic effect in different combinations against both types of bacteria. It is remarkable that the combinations could enhance the sensitivity of E. coli to vancomycin 16-fold to which it is normally insensitive. We have provided proof for the concept, that combinations of known antibiotics with modern phytotherapeutics can expand the spectrum of useful therapeutics.

In this paper, we introduce a simple to manufacture, emission current controlled, miniaturized non-radioactive electron source to provide free electrons at atmospheric pressure. In atmospheric pressure chemical ionization as usually used in ion mobility spectrometry radioactive beta minus sources provide free electrons with high kinetic energy to initiate a chemical gas phase ionization of the analytes. Here, classical thermionic emission from a heat controlled tungsten filament in vacuum is used to generate free electrons. These are then accelerated towards an electron transparent 300 nm thin Si3N4-membrane through which the electrons are transferred from vacuum to atmospheric pressure. Both, the emitted electron current and the average kinetic electron energy can be controlled. For similar ionization processes as compared to radioactive beta minus sources we operate the electron source with an electron emission current at atmospheric pressure of 50 pA – corresponding to an activity of 300 MBq – and an average kinetic electron energy of 8.6 keV.

We report on a 68 years old survivor of an out-of-hospital cardiac arrest with favorable neurological outcome following prolonged cardiopulmonary resuscitation (CPR 59 min) until return of spontaneous circulation (ROSC) due to ST-elevation myocardial infarction (STEMI). The case demonstrates the beneficial effect of an optimal rescue chain including basic life support performed by trained bystanders, short response time of the emergency medical service, uninterrupted CPR during transportation using a mechanical chest compression system (LUCAS®), in combination with optimal intensive care management of cardiogenic shock after ROSC including multivessel emergency percutaneous coronary intervention (PCI) and intravascular therapeutic hypothermia (Coolgard®-System).

The applicability of the dynamic soil model CHUM-AM was tested to simulate concentrations of Cd, Pb and Hg in five Swiss forest soils. Soil cores of up to 50 cm depth were sampled and separated into two defined soil layers. Soil leachates were collected below the litter by zero-tension lysimeters and at 15 and 50 cm soil depths by tension lysimeters over two years. The concentrations of Cd, Pb and Hg in the solid phase and soil solution were measured by ICP-MS (Cd, Pb) or CV-AFS (Hg). Measured metal concentrations were compared with modelled concentrations using CHUM-AM. Additionally we ran the model with three different deposition scenarios (current deposition; maximum acceptable deposition according to the Swiss ordinance on Air Pollution Control; critical loads according to CLRTAP) to predict metal concentrations in the soils for the next 1000 years. Assuming current loads concentrations of Cd and Pb showed varying trends (increasing/decreasing) between the soils. Soils rich in organic carbon or with a high pH value showed increasing trends in Cd and Pb concentrations whereas the concentrations in the other soils decreased. In contrast Hg concentrations are predicted to further increase in all soils. Critical limits for Pb and Hg will partly be exceeded by current loads or by the critical loads proposed by the CLRTAP but the critical limits for Cd will rarely be reached within the next 1000 years. In contrast, maximal acceptable deposition will partly lead to concentrations above the critical limits for Pb in soils within the next 400 years, whereas the acceptable deposition of Cd will not lead to concentrations above the proposed critical limits. In conclusion the CHUM-AM model is able to accurately simulate heavy metal (Cd, Pb and Hg) concentrations in Swiss forest soils of various soil properties.

Background:Subgroup analyses of the Latarjet procedure have suggested that age over 40 years is a risk factor for dislocation arthropathy.Purpose:To analyze long-term results of the open Latarjet procedure for recurrent anterior shoulder dislocation in patients at least 40 years of age.Study Design:Case series; Level of evidence, 4.Methods:A total of 39 consecutive patients (40 shoulders) with a mean age of 48 years (range, 40-66 years) at surgery were evaluated at a mean follow-up of 11.0 years (range, 8-16 years). Of these, 15 patients (38%) had undergone previous soft tissue stabilization surgery. Long-term results were assessed clinically and radiographically, including computed tomography scanning at final follow-up.Results:No recurrence of dislocation was noted. Subluxation had occurred in 3 patients (8%), and apprehension persisted in 5 patients (13%). The total Walch-Duplay score averaged 89 points at the final follow-up, and the mean Subjective Shoulder Value (60%-91%) had improved significantly ( P < .001). In total, 36 patients rated their result as excellent, 3 as good. Further, 6 patients (15%) underwent joint-preserving reoperation, and 1 patient (3%) had reverse total shoulder arthroplasty for severe dislocation arthropathy. Dislocation arthropathy was severe in 14 patients (37%) and had progressed by at least 2 grades in 17 patients (45%). Patients with severe dislocation arthropathy had already shown degenerative changes preoperatively as opposed to those who ultimately had no or moderate dislocation arthropathy (n = 24) ( P < .001). Progression of dislocation arthropathy was associated with lateral (>1 mm) graft positioning ( P < .001) and older age at surgery ( r = 0.58; P < .001).Conclusion:The open Latarjet procedure for recurrent anterior shoulder instability in patients older than 40 years reliably restores stability and leads to high patient satisfaction. This procedure is, however, associated with a substantial rate of advanced but clinically mild symptomatic dislocation arthropathy, which is associated with the degree of preoperative joint degeneration, older age at surgery, and lateral graft placement.

Ion mobility spectrometry (IMS) is a well known method for fast trace gas detection in air. Having simple instrumentation, IMS is especially suited when portability and highest sensitivity are required. However, due to competing chemical ionization processes in the reaction region of IMS, it can be difficult or even impossible to detect small amounts of certain substances in a complex mixture. A prominent example is the detection of low benzene concentrations in the presence of higher toluene concentrations. In this paper we present experimental results of simultaneous toluene and benzene detection by using a pulsed electron source for ionization and demonstrate how this can help to overcome the major issue of atmospheric pressure chemical ionization (APCI).

Telomerase inhibition causes progressive telomere shortening and cellular senescence, which constitutes a universal barrier to tumor growth and therefore an attractive target for tumor therapy. To expand our previous studies, we investigated the global effects of telomere dysfunction on the proteome of tumor cells in order to find novel senescence biomarkers. Telomerase-deficient HCT-116 cell clones were analyzed by a quantitative proteomic approach using isotope-coded protein labeling (ICPL) and nanoflow-HPLC-MS/MS. Stringent reduction of the extensive proteomic data from this tumor cell model revealed a list of 59 markers including proteins identified in our former studies and a number of novel proteins involved in tumorigenesis and metastasis such as SFN, S100A4, ANXA2, and LGALS1. A loss of the chromatin protein HMGB2 was demonstrated not only in various telomerase-inhibited clones of different tumor cell lines, but also in normal human fibroblasts undergoing replicative senescence and in aging telomerase knockout mice. Impressively, a coherent and dense network of protein–protein interactions for the bulk of the markers and their implementation in signaling pathways involving key regulators for tumorigenesis were revealed. These results have an impact on the understanding of telomere- and senescence-related signal transduction in tumor cells in consideration of the general lack of senescence markers. Biological significance Induction of cellular senescence constitutes a potent concept for tumor therapy which interferes with immortalization and additional hallmarks of cancer. The application of a powerful quantitative proteomic approach using isotope-coded protein labeling to an approved model for senescence represented by telomerase inhibited tumor cells led to the identification of novel candidate biomarkers for telomere dysfunction and replicative senescence. Thereby, the identified markers not only fit in the context of the investigated processes with a relevance for additional hallmarks of cancer but are also involved in a strong interaction network and integrated in canonical pathways centered around key cancer-relevant proteins. These potential markers alone or in combination will significantly extend the view on telomere-associated signal transduction in tumor cells and contribute to the field of cellular senescence and aging in consideration of the general lack of biomarkers in this regard.

Predictors of long-term outcome after ST-elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) are incompletely understood, including the influence of successful coronary reperfusion.We analysed clinical and procedural data as well as 1-year outcome of 72 consecutive patients who underwent primary coronary intervention (PCI) after witnessed OHCA and STEMI and compared the results with 695 patients with STEMI and PCI, but without OHCA. Neurological recovery after OHCA was assessed using the Cerebral Performance Category (CPC) scale.PCI was successful in 83.3% after OHCA vs. 84.3% in the non-OHCA group (p=0.87). One-year mortality was 34.7% vs. 9.5% (p0.001). 58.3% of the OHCA-patients showed complete neurological recovery (CPC 1) or moderate neurological disability (CPC 2). Another 6.9% showed severe cerebral disability (CPC 3) or permanent vegetative status (CPC 4). Delay from collapse until start of Advanced Cardiopulmonary Life Support (ACLS) was shorter for survivors with CPC status ≤2 (median 1 min, range 0-11 min) compared to non-survivors or survivors with CPC status2 (median 8 min, range 0-13 min), p0.0001. Age-adjusted multivariate analysis identified 'unsuccessful PCI', 'vasopressors on admission' and 'start of ACLS after6 min' as independent predictors of negative long-term outcome (death or CPC2).Mortality is high in patients with STEMI complicated by OHCA - even though PCI was performed with the same success rate as in patients without OHCA. The majority of survivors had favourable neurological outcomes at 1 year, especially if advanced life support had been started within ≤6 min and PCI was successful.

Background Heterotopic ossification (HO) frequently causes complications following orthopaedic and trauma surgery and may drastically reduce the postoperative outcome due to pain and joint contracture. Current therapeutic options include NSAID's and local radiation. However, both options of prevention show disadvantages such as delayed fracture healing and impaired ossification as well as other side effects. 9 Our goal was to investigate a novel approach in the prevention of heterotopic ossification by pharmacologically interfering with the molecular signalling pathways involved in this process. Hypoxia leads to numerous effects on a cellular level, one of which is the activation of the transcriptional complex hypoxia-inducible factor (HIF). 19 Among several other actions, the HIF1-α signalling pathway in turn regulates angiogenesis through induction of the expression of vascular endothelial growth factor (VEGF). 21 We hypothesised that by pharmacologically interfering with the HIF-1α signalling pathway, the amount of HO formation may be reduced. Echinomycin is a known inhibitor of HIF-1-alpha and was used in our study with the aim to prevent HO from forming. Methods We examined the effect of Echinomycin on HO formation in a murine model where an Achilles tenotomy was performed. This has previously been shown to reliably produce islets of heterotopic ossification within the soft tissue of mouse hind limbs at 10 weeks after surgery. The control group underwent Achilles tenotomy only, whereas the Echinomycin group additionally received Echinomycin subcutaneously. After trial completion, the limbs were harvested and Micro-CT was performed. Heterotopic bone volume was then identified in 3d images and quantified. Results We found a highly significant reduction in the bone volume following subcutaneous administration of Echinomycin compared to the control group. Conclusion Although a substantial reduction could be achieved, it was not possible to completely prevent heterotopic ossification from forming. Further studies have yet to be conducted to optimise the results by altering the dosage and duration of administration as well as investigate the mechanism by which Echinomycin led to the reduction of HO formation.

Background and purpose Patients with severe acute stroke are at high risk for systemic infections which are associated with an increase in morbidity and mortality; nevertheless current guidelines do not recommend prophylactic antibiotic therapy. Sensitive detection of pathogens in the blood is desirable to guide early antibiotic therapy. We studied the yield of blood culture testing and microbiological PCR-based methods for early detection of post-stroke bacteremia. Methods Serial blood culture tests either during the first fever episode (> 38.5 °C) or 24 h after admission were performed every 12 h for up to 96 h after admission. Additionally, microbiological PCR-based techniques for the detection of microbiological pathogens were performed once during the first fever episode prior to initiating antibiotic treatment. Results 21 severely affected acute stroke patients deemed at high risk for systemic infections (median (interquartile range (IQR)) at admission NIHSSS 19 (15–30) were enrolled; 20 patients were intubated within 5 h after ICU admission. All patients developed clinical signs and laboratory constellations compatible with systemic infections within 36 h after admission. However, no patient had pathogenic bacteria either in serial blood culture analyses during the first 96 h after admission or by PCR-based techniques. Conclusions Very early bacteremia seems not to be a feature of severe stroke in patients despite signs of early immune system depression and frequent subsequent evidence of infection including pneumonia. Consequently our data suggests, that routine early blood-based standard or molecular microbiological assays do not reveal bacteremia, this finding questions the usefulness of their routine performance in this context.

a substantial proportion of non-small-cell lung cancer (NSCLC), and adenocarcinoma in particular, depends on a so-called ‘driver mutation’ for their malignant phenotype. This genetic alteration induces and sustains tumorigenesis, and targeting of its protein product can result in growth inhibition, tumor response and increased patient survival. NSCLC can thus be subdivided into clinically relevant molecular subsets. Mutations in EGFR best illustrate the therapeutic relevance of molecular classification. This article reviews the scope of presently known driving molecular alterations, including ROS1, BRaF, KRaS, HER2 and PIK3Ca, with a special emphasis on aLK rearrangements, and outlines their potential therapeutic applications.

Ion mobility spectrometry (IMS) is a well-known technique applied to detect hazardous substances in ambient air. Consequently, it has been used for many years for the detection of chemical warfare agents, toxic substances or illegal drugs. The main advantages are the small size of IMS instruments and the very high sensitivity in the range of a few parts per billion. However, one major disadvantage is the fairly difficult interpretation of spectra especially when mixtures of substances are involved. Spectra recorded with a pulsed IMS, in which delay times can be inserted between ion formation and ion detection, can simplify this task due to the distinct behavior that monomer and dimer peaks exhibit with varying delay times. The discrimination between monomer and dimer signals would normally require further experimental efforts (e.g. a mass spectrometer) with disadvantages regarding the portability of the device. This paper describes how a pulsed electron gun used in a standard IMS device allows for this discrimination without compromising any of the benefits IMS devices offer.

Objectives This study sought to define the impact of paclitaxel-coated balloon angioplasty for treatment of drug-eluting stent restenosis compared with uncoated balloon angioplasty alone. Background Drug-coated balloon angioplasty is associated with favorable results for treatment of bare-metal stent restenosis. Methods In this prospective, single-blind, multicenter, randomized trial, the authors randomly assigned 110 patients with drug-eluting stent restenoses located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty. Dual antiplatelet therapy was prescribed for 6 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was late lumen loss. The secondary clinical endpoint was a composite of cardiac death, myocardial infarction attributed to the target vessel, or target lesion revascularization. Results There was no difference in patient baseline characteristics or procedural results. Angiographic follow-up rate was 91%. Treatment with paclitaxel-coated balloon was superior to balloon angioplasty alone with a late loss of 0.43 ± 0.61 mm versus 1.03 ± 0.77 mm (p Conclusions Paclitaxel-coated balloon angioplasty is superior to balloon angioplasty alone for treatment of drug-eluting stent restenosis. (PEPCAD DES–Treatment of DES-In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting PTCA Catheter [PEPCAD-DES]; NCT00998439 )

Purpose To obtain a diagnosis of tuberculosis in patients with a specific subset of uveitis, serpiginous-like choroiditis. This subset has been suspicious for tuberculous etiology in single case reports and old textbooks. Design Retrospective evaluation of a diagnostic test in a specific uveitis cohort. Methods QuantiFERON is an approved, antigen-specific test that utilizes synthetic peptides representing Mycobacterium tuberculosis proteins. After incubation, interferon γ secreted by T lymphocytes in response to these antigens is measured. We used the test in 21 of 26 patients identified from our database with serpiginous-like choroiditis. Rates of QuantiFERON positivity were compared to a group of healthy hospital employees (n = 208), another group of healthy hospital workers after tuberculosis contact (n = 117), and a group of randomly tested patients with other uveitis forms (n = 45). Results Eleven of 21 serpiginous-like choroiditis patients (52%) were tested positive. The rate of QuantiFERON positivity in the healthy control groups was 8.7% and 0.9%, and 13% in the other uveitis subsets. Four of the QuantiFERON-positive serpiginous-like choroiditis patients were treated with standard anti-tuberculostatic therapy; three finished the course and improved. Seven patients are either stable without therapy (n = 4) or on low-dose prednisone (n = 3). Conclusions QuantiFERON testing revealed a high number of positive patients, which indicates a tuberculous etiology in this uveitis subset. Whether bacterial activity or secondary immunologic processes are causative remains a matter of speculation.

Ion mobility spectrometry is a well-known method for detecting hazardous compounds in air. Detection limits in the low ppb range and fast response times make this technique more and more popular. Typical applications are the detection of chemical warfare agents, toxic industrial compounds, explosives and drugs. This paper describes the concept and preliminary results of a simple planar ion-focusing aspiration condenser as an ion mobility spectrometer (IMS). Compared to other aspiration condenser IMS with identical ion carrier gas and drift gas, our design has separate gas flows. This allows fluidic focusing of the ion carrier gas by means of geometric constrains. Thus, ions are focused before separation, which results in improved separation power. Furthermore, humidity in the ion carrier gas does not effect peak position in the ion mobility spectrum when using dry drift gas. In addition, the system is easy to fabricate at low-cost, has small dimensions and low power consumption. First measurements of 1-Octanol in air demonstrate the potential of this novel concept.

The detection of driver mutations in the epidermal growth factor receptor (EGFR), the rearrangement of anaplastic lymphoma kinase (ALK) genes and the subsequent development of targeted therapy have transformed the treatment of lung cancer. In a Caucasian population, as illustrated by the Biomarker France database, these alterations represent 9.4% and 4.0%, respectively, in 10,000 samples of non-small-cell lung cancer (NSCLC) [1]. Of these patients, 56.9% received treatment according to their molecular profile, either with labelled drugs or in a bio-guided trial. Similarly, the Lung Cancer Mutation Consortium, after testing more than 1000 patients with lung adenocarcinoma, found 15% to harbour an EGFR mutation and 8% an ALK rearrangement [2]. An actionable driver alteration was detected in 62% of these tumours. The use of targeted therapies has raised practical questions related to therapy sequences and durations, the role of chemotherapy, the role of combination with chemotherapy, the validity of Response Evaluation Criteria in Solid Tumours (RECIST) criteria, utility of therapeutic rechallenge with the same drugs and several additional issues that arise in the wake of all significant medical progress. This article will address some of these questions and highlight some areas of controversy.

Wafer-level fabrication of integrated enzyme-based BioMEMS usually requires high temperature wafer-bonding techniques such as anodic bonding. Enzymes denature at comparatively low temperatures. Thus, enzymes need to be immobilized after wafer bonding. A convenient in-device immobilization method is presented allowing wafer-level patterning of enzymes inside micro-scale flow channels after wafer bonding. Enzymes are entrapped in a poly(vinyl alcohol)-styrylpyridinium (PVA-SbQ) membrane crosslinked by UV exposure through a transparent top wafer. The reaction kinetics of immobilized glucose oxidase is investigated in more detail. A low apparent Michaelis constant of 3.0 mM is determined indicating a rapid diffusion of glucose into the PVA-SbQ membrane as well as an oxygen-limited maximum catalytic rate. The entrapped glucose oxidase preserves its native properties since it is not chemically modified. Furthermore, the active PVA-SbQ membrane can be dehydrated in a vacuum and later rehydrated in buffer solution without significant loss of enzyme activity. An integrated enzyme-based glucose sensor fabricated on a wafer-level using in-device immobilization is described to demonstrate the potential of this novel technique. The sensor is part of a disposable microneedle-based continuous glucose monitor. The stability of glucose oxidase entrapped in PVA-SbQ is sufficient to continuously operate the sensor at 25 °C for 24 h.