Factors associated with return-to-work outcomes in inpatient rehabilitation - a systematic scoping review.

Inpatient rehabilitation is common in Germany to improve return-to-work outcomes. The objective of this systematic scoping review was to identify factors associated with return-to-work outcomes in musculoskeletal, psychological and oncological health conditions to improve tailoring of rehabilitation therapies. A search was completed in Embase, Medline, PsycInfo and AMED until May 2023 for articles investigating inpatient rehabilitation including working-age patients with oncological, musculoskeletal, or psychological diseases using a quantitative design and reporting factors associated with return-to-work outcomes. Screening of all titles and abstracts was completed by one reviewer, full texts were read by two reviewers. Quality appraisal and data extraction was completed by two reviewers. Data was analysed using a narrative synthesis. Eighteen studies of moderate quality were included. The review identified a wide range of return-to-work parameters including employment status, work ability, sickness absence, retirement status and duration of employment since rehabilitation. In addition, 48 psychological, health- and work-related factors associated with return-to-work parameters were identified. Only one RCT investigated the relationship between a depression prevention intervention and a return-to-work outcome (work ability), which showed a significant effect. In addition to the depression prevention intervention, only the factor 'health literacy' could be considered modifiable and be addressed as part of an inpatient rehabilitation programme. Furthermore, gradual work reintegration programs and/or workplace interventions in addition to inpatient rehabilitation should be further explored to improve return-to-work outcomes.

Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

Coherence in macroscopic high harmonic generation for spatial focal phase distributions of monochromatic and broadband Gaussian laser pulses.

Efficient application of ultrafast laser sources from high harmonic generation requires an understanding of how the spectrum can be controlled - the extent of the highest harmonics and the strength and cleanness of the harmonic lines. We study one important aspect in the coherent build-up of macroscopic high-order harmonic generation, namely the impact of different phase distributions in the focal area on the features of the generated radiation. Specifically, we compare the high harmonic signals for the commonly-used Gouy distribution of a monochromatic beam with those for the phase distribution of a short broadband Gaussian pulse. To this end, we apply a theoretical model in which the microscopic yields are obtained via interpolation of results of the time-dependent Schrödinger equation, which are then used in an individual-emitter approach to determine the macroscopic signals. Regions of poor and good coherent build-up as a function of the position of the gas jet are identified using measures for the strength of the harmonic lines and for the impact of off-harmonic radiation. While the largest extent of the spectra as well as the strongest contribution of off-harmonic radiation is found for positioning the gas jet after the focus for both distributions, the relative strength of the harmonics is overall weaker for the short Gaussian pulse distribution and the spectra differ for a gas jet positioned at the focus. These differences are mainly caused by the additional dependence of the focal phase in the transverse direction for the short Gaussian pulse distribution.

Characterization of vacuum and deep ultraviolet pulses via two-photon autocorrelation signals.

Characterization of ultrashort vacuum and deep ultraviolet pulses is important in view of applications of those pulses for spectroscopic and dynamical imaging of atoms, molecules, and materials. We present an extension of the autocorrelation technique, applied for measurement of the pulse duration via a single Gaussian function. Analytic solutions for two-photon ionization of atoms by Gaussian pulses are used along with an expansion of the pulse to be characterized using multiple Gaussians at multi-color central frequencies. This approach allows one to use two-photon autocorrelation signals to characterize isolated ultrashort pulses and pulse trains, i.e., the time-dependent amplitude and phase variation of the electric field. The potential of the method is demonstrated using vacuum and deep ultraviolet pulses and pulse trains obtained from numerical simulations of macroscopic high harmonic spectra.

Loop-mediated isothermal amplification: Development, validation and application of simple and rapid assays for quantitative detection of species of Arcobacteraceae family- and species-specific Aliarcobacter faecis and Aliarcobacter lanthieri.

AIM: The family Arcobacteraceae formerly genus Arcobacter has recently been reclassified into six genera. Among nine species of the genus Aliarcobacter, Aliarcobacter faecis and Aliarcobacter lanthieri have been identified as emerging pathogens potentially cause health risks to humans and animals. This study was designed to develop/optimize, validate and apply Arcobacteraceae family- and two species-specific (A. faecis and A. lanthieri) loop-mediated isothermal amplification (LAMP) assays to rapidly detect and quantify total number of cells in various environmental niches. METHODS AND RESULTS: Three sets of LAMP primers were designed from conserved and variable regions of 16S rRNA (family-specific) and gyrB (species-specific) genes. Optimized Arcobacteraceae family-specific LAMP assay correctly amplified and detected 24 species, whereas species-specific LAMP assays detected A. faecis and A. lanthieri reference strains as well as 91 pure and mixed culture isolates recovered from aquatic and faecal sources. The specificity of LAMP amplification of A. faecis and A. lanthieri was further confirmed by restriction fragment length polymorphism analysis. Assay sensitivities were tested using variable DNA concentrations extracted from simulated target species cells in an autoclaved agricultural water sample by achieving a minimum detection limit of 10 cells mL-1 (10 fg). Direct DNA-based quantitative detection, from agricultural surface water, identified A. faecis (17%) and A. lanthieri (1%) at a low frequency compared to family-level (93%) with the concentration ranging from 2·1 × 101 to 2·2 × 105 cells 100 mL-1 . CONCLUSIONS: Overall, these three DNA-based rapid and cost-effective novel LAMP assays are sensitive and can be completed in less than 40 min. They have potential for on-site quantitative detection of species of family Arcobacteraceae, A. faecis and A. lanthieri in food, environmental and clinical matrices. SIGNIFICANCE AND IMPACT OF THE STUDY: The newly developed LAMP assays are specific, sensitive, accurate with higher reproducibility that have potential to facilitate in a less equipped lab setting and can help in early quantitative detection and rate of prevalence in environmental niches. The assays can be adopted in the diagnostic labs and epidemiological studies.

Evaluation of different target genes for the detection of Salmonella sp. by loop-mediated isothermal amplification.

The loop-mediated isothermal amplification (LAMP) technique was used to investigate six salmonella-specific sequences for their suitability to serve as targets for the pathogen identification. Sequences selected for designing LAMP primers were genes invA, bcfD, phoP, siiA, gene62181533 and a region within the ttrRSBCA locus. Primers including single nucleotide polymorphisms were configured as degenerate primers. Specificity of the designed primer sets was determined by means of 46 salmonella and 32 other food- and waterborne bacterial reference species and strains. Primers targeting the ttrRSBCA locus showed 100 % inclusivity of target and exclusivity of other test species and strains. Other primer sets revealed deficiencies, especially regarding Salmonella enterica subsp. II-IV and Salmonella bongori. Additionally, primers targeting the siiA gene failed to detect S. enterica subsp. enterica serotypes Newport and Stanley, whereas bcfD primers did not amplify DNA of S. enterica subsp. enterica serotype Schleissheim. TtrRSBCA primers, providing short detection times and constant melting temperatures of amplification products, achieved best overall performance.

[Identification of rheumatological health apps in the Apple app store applying the "semiautomatic retrospective app store analysis" method : A longitudinal observation]. / Identifikation rheumatologischer Gesundheits-Apps im Apple App Store mit der Methode der "semiautomatischen retrospektiven App Store-Analyse" : Eine longitudinale Betrachtung.

BACKGROUND: The Apple and Google app stores offer a wide range of health apps. It is still a challenge to find valuable and qualified apps. OBJECTIVE: Can German language apps be identified using the "semiautomated retrospective app store analysis" (SARASA) method for the field of rheumatology? MATERIAL AND METHOD: The SARASA is a semiautomated method to select and characterize apps listed in the app store. After the first application in February 2018 SARASA was applied again to the Apple app store in February 2020. RESULTS: In February 2018 it was possible to acquire metadata for 103,046 apps and in February 2020 data for 94,735 apps that were listed in the category "health and fitness" or "medicine" in Apple's app store frontend for Germany. After applying the search terms 59 apps with a German language app description were identified for the field of rheumatology in 2018 and 53 apps in 2020. For these, more detailed manual reviews seem worthwhile. In 2018, the apps found were more likely to address patients than physicians and this was more balanced in 2020. In addition, it became apparent that for certain diseases there was no app developer activity. The percentage breakdown of matches by search term revealed substantial fluctuations in the app market when comparing 2018 to 2020. DISCUSSION: The SARASA method provides a useful tool to identify apps from app stores that meet predefined, formal criteria. Subsequent manual checks of the quality of the contents are still necessary. Further development of the SARASA method and consensus and standardization of quality criteria are worthwhile. Quality criteria should be considered for offers of mobile health apps in app stores.

Tolerance and microbiological efficacy of cefepime or piperacillin/tazobactam in combination with vancomycin as empirical antimicrobial therapy of prosthetic joint infection: a propensity-matched cohort study.

BACKGROUND: The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading us to propose cefepime as an alternative since 2017 in our reference centre. OBJECTIVES: To compare microbiological efficacy and tolerance of these two EAT strategies. METHODS: All adult patients with PJI empirically treated with vancomycin+cefepime (n = 89) were enrolled in a prospective observational study and matched with vancomycin+piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxic agents. The two groups were compared using Kaplan-Meier curve analysis, and non-parametric tests regarding the proportion of efficacious empirical regimen and the incidence of empirical therapy-related adverse events (AE). RESULTS: Among 146 (82.0%) documented infections, the EAT was considered efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin/tazobactam- and cefepime-treated patients, respectively (P = 1.000). The rate of AE, particularly AKI, was significantly higher in the vancomycin+piperacillin/tazobactam group [n = 27 (30.3%) for all AE and 23 (25.8%) for AKI] compared with the vancomycin+cefepime [n = 13 (14.6%) and 6 (6.7%)] group (P = 0.019 and <0.001, respectively), leading to premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). The two groups were not significantly different regarding their comorbidities, and AKI incidence was not related to vancomycin plasma overexposure. CONCLUSIONS: Based on the susceptibility profile of bacterial isolates from included patients, microbiological efficacy of both strategies was expected to be similar, but vancomycin + cefepime was associated with a significantly lower incidence of AKI.

Macroscopic properties of high-order harmonic generation from molecular ions.

High harmonic spectroscopy utilizes the extremely nonlinear optical process of high-order harmonic generation (HHG) to measure complex attosecond-scale dynamics within the emitting atom or molecule subject to a strong laser field. However, it can be difficult to compare theory and experiment, since the dynamics under investigation are often very sensitive to the laser intensity, which inevitably varies over the Gaussian profile of a typical laser beam. This discrepancy would usually be resolved by so-called macroscopic HHG simulations, but such methods almost always use a simplified model of the internal dynamics of the molecule, which is not necessarily applicable for high harmonic spectroscopy. In this Letter, we extend the existing framework of macroscopic HHG so that high-accuracy ab initio calculations can be used as the microscopic input. This new (to the best of our knowledge) approach is applied to a recent theoretical prediction involving the HHG spectra of open-shell molecules undergoing nonadiabatic dynamics. We demonstrate that the predicted features in the HHG spectrum unambiguously survive macroscopic response calculations, and furthermore they exhibit a nontrivial angular pattern in the far field.

[The role of the gut microbiome in idiopathic Parkinson's disease]. / Die Rolle des Darmmikrobioms beim idiopathischen Parkinson-Syndrom.

BACKGROUND: In recent years studies have provided increasing evidence suggesting an association between the (gut) microbiome and idiopathic Parkinson's disease (IPD). OBJECTIVE: The aim of this article is to summarize and evaluate existing evidence with respect to the relevance of the (gut) microbiome for IPD. MATERIAL AND METHODS: An analysis and critical review of studies in the field of IPD and (gut) microbiome were carried out. The resulting potential perspectives and therapeutic strategies are discussed. RESULTS: Despite partially divergent results between different studies (potentially due to the applied methods and variance in the composition of the investigated cohorts), there is an overlap between studies indicating an association between IPD, the microbiome and microbial metabolites. Nevertheless, the cause-effect relationship between IPD and the microbiome has still not been clarified. Taken together, existing evidence supports a potentially relevant role for the microbiome with respect to typical disease symptoms and pathogenesis of the disease. CONCLUSION: Over the past 5 years there has been an enormous increase in the evidence with respect to the relevance of the microbiome for IPD. While early work in this field was mainly descriptive, new diagnostic methods provide evidence for the underlying mechanisms and the complex interactions between man as the host, the human immune system, the enteric nervous system, gut microbiota and microbial metabolites. A relatively novel and clinically relevant field of research is how the gut microbiome can influence the success of oral pharmacotherapy and whether substitution of specific microbiome components might be used either for future therapeutic or prophylactic strategies.

Review: Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis.

Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter-rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.

Development and validation of a loop-mediated isothermal amplification assay-a rapid and sensitive detection tool for Mycobacterium avium subsp. paratuberculosis in small ruminants.

AIMS: The aim of this study was to design an assay for the identification of Mycobacterium avium subsp. paratuberculosis (MAP) to be used in faeces and milk samples of small ruminants with a loop-mediated isothermal amplification (LAMP) system, as a time-saving and user-friendly method in contrast to real-time PCR. METHODS AND RESULTS: For the detection of MAP in milk and faeces of small ruminants, we developed a set of primers, specific for the target gene ISMap02. The analytical sensitivity of LAMP, when targeting ISMap02, showed a DNA detection limit of 10 fg µl-1 . After performing spiking experiments with two MAP reference strains, DSM 44133 and ATCC 19698T , the limit of detection, using the LAMP protocol described herein were 3·8 MAP CFU per ml milk and 12·5 MAP CFU per gram faeces. All LAMP results during the establishment of the assay were compared to those of the real-time PCR results. An internal amplification control was incorporated into the assay to exclude false-negative results produced and had no significant negative impact on the analytical sensitivity. Validation of the assay was confirmed by testing field samples of faeces and revising the results with real-time PCR. CONCLUSION: Our study conducted the first MAP detection system with a LAMP targeting ISMap02. Due to the positive results we encourage the use of LAMP in combination with ISMap02, when detecting MAP in faeces samples, as an alternative to targeting other genes as f57 or IS900. Further research on MAP detection in different matrices like raw milk, tissue or sperm with this system is recommended. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new achievements in MAP diagnostic. Especially small ruminants do not show signs of diarrhoea until the terminal stage of the illness. The greatest task in fighting MAP is to rule out animals, which shed MAP with faeces and milk before showing symptoms of Johne's disease. Worldwide there is a need to eradicate animals, which are low MAP shedders to stop the illness spreading in animal holdings. MAP detection with LAMP is time saving, easy to use, does not need expensive equipment, as, for example, PCR kits and can be used without access to laboratories. The target gene ISMap02 was shown to be a specific insertion element for MAP and is a reliable aim in future MAP detection studies.

Adiponectin, leptin and insulin in breast milk: associations with maternal characteristics and infant body composition in the first year of life.

BACKGROUND/OBJECTIVES: Breastfeeding may protect against excessive weight gain during infancy. However, the breast milk components responsible for this effect are unknown. We examined the variation of three breast milk hormones (adiponectin, leptin and insulin) according to maternal characteristics and determined their association with infant body composition. SUBJECTS/METHODS: We studied a representative subset of 430 breastfed infants in the CHILD birth cohort. Breast milk was collected at 4 months postpartum and hormone concentrations were measured using the MesoScale Discovery System. Weight-for-length (WFL) and body mass index (BMI) z-scores were calculated according to the World Health Organization reference standard from infant anthropometrics measured at 4 months and 1 year. Maternal BMI and demographics were self-reported. RESULTS: Breast milk hormone concentrations varied widely between mothers. The geometric mean (range) was 19.4 (3.7-74.4) ngml-1 for adiponectin; 361 (31-3968) pgml-1 for leptin; and 589 (53-5557) pgml-1 for insulin. Maternal BMI was positively correlated with breast milk insulin (r=+0.40, P<0.0001) and leptin (r=+0.71, P<0.0001), but not adiponectin (r=-0.02, P=0.68). Breast milk hormone concentrations were also associated with maternal ethnicity, parity and breastfeeding exclusivity at sample collection. Independent of these factors and maternal diabetes, smoking and breastfeeding duration, higher breast milk leptin was associated with lower infant WFL z-score at 4 months (ß -0.67, 95% confidence interval (CI): -1.17, -0.17 for highest vs lowest quintile) and 1 year (ß -0.58, 95% CI: -1.02, -0.14). Insulin showed a U-shaped association, with intermediate concentrations predicting the lowest infant WFL z-score at 4 months (ß -0.51, 95% CI: -0.87, -0.15 for third vs lowest quintile) and 1 year (ß -0.35, 95% CI: -0.66, -0.04). Similar results were seen with infant BMI. Breast milk adiponectin was not significantly associated with infant body composition. CONCLUSIONS: Breast milk hormone concentrations were associated with several fixed and modifiable maternal characteristics. Higher concentrations of leptin and intermediate concentrations of insulin were associated with lower infant WFL in the first year of life.

Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: Effects on allergic diseases.

BACKGROUND: While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined. OBJECTIVE: We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort. METHODS: Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group. RESULTS: Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years; those in the "inhalant sensitization" group had the highest risk for allergic rhinitis; children in the "transient sensitization" group were at an increased risk for food allergy; while children in the "persistent sensitization" group had the highest risk for all allergic diseases. CONCLUSION AND CLINICAL RELEVANCE: There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.

Review: Animal models of acquired epilepsy: insights into mechanisms of human epileptogenesis.

In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, that is, segmental neuronal cell loss and concomitant astrogliosis. Many TLE patients report on transient brain insults early in life, which is followed by a 'latency' period lacking seizure activity of months or even years before chronic recurrent seizures start. The plethora of structural and cellular mechanisms that convert the hippocampal formation to become chronically hyperexcitable after a transient insult to the brain are summarized under the term epileptogenesis. In contrast to the obstacles arising for experimental studies of epileptogenesis aspects in human surgical hippocampal tissue, recent animal model approaches allow insights into mechanisms of epileptogenesis. Relevant models of transient brain insults in this context comprise several distinct types of lesions including excitoxic status epilepticus (SE), electrical seizure induction, traumatic brain injury, induction of inflammatory processes by hyperthermia and viral inflammation and others. In pathogenetic terms, aberrant transcriptional and epigenetic reprogramming, acquired channel- and synaptopathies, neuronal network and blood-brain barrier dysfunction as well as innate and adaptive immunity-mediated damage play major roles. In subsequent steps, respective animal models have been used in order to test whether this dynamic process can be either retarded or even abolished by interfering with epileptogenic mechanisms. Well-controlled subsequent analyses of epileptogenic cascades characterized in animal models using carefully stratified human hippocampal biopsies to exploit the unique opportunities given by these rare and precious brain tissue samples aim to translate into novel antiepileptogenic approaches. Respective preclinical tests can open entirely new perspectives for tailor-made treatments in patients with the potential to avoid the emergence of chronic focal seizure events.

Gender associated developmental trajectories of SDQ-dysregulation profile and its predictors in children.

BACKGROUND: Severe mood dysregulation is common in childhood and can be highly impairing. The Dysregulation Profile (DP) can be considered as a broader phenotype of emotional dysregulation, including affect, cognition and behaviour. Since mood dysregulation may persist, but differently in boys and girls, the gender associated course needs to be considered longitudinally to gain a better insight in order to support the children more adequately. This study is focusing on gender associated subgroup trajectories of the Strengths and Difficulties Questionnaire-Dysregulation Profile (SDQ-DP) in middle childhood (9-13 years of age) and includes the potential impact of clinical and psychosocial characteristics. METHOD: The data set was available from the BELLA study on mental health and well-being in children and adolescents, which is the mental health module of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A representative epidemiological sample of 564 children living in Germany was examined at three assessment points over 2 years (data collection 2003-2006). The SDQ-DP of children aged 9-13 years was evaluated using Latent Class Growth Analysis (LCGA). RESULTS: For both genders three trajectories with low (girls 67.0% and boys 59.5%), moderate (girls 28.0% and boys 31.7%) and high SDQ-DP (girls 5.0% and boys 8.8%) scores were detected. The courses of low and moderate subgroups were stable, while in the high SDQ-DP subgroup boys showed a decreasing and girls an increasing trend in symptom severity on a descriptive level. The results of the multinomial logistic regression analyses revealed a significant influence of mainly externalising but also internalising problems both increasing the risk of moderate and high SDQ-DP in both genders. Good quality of life was a protective factor for the SDQ-DP course in all subgroups. CONCLUSION: In addition to the known clinical and scientific value of the SDQ-DP, three distinguishable trajectories of SDQ-DP in boys and girls could be found. High externalising problems at the beginning of the trajectory were associated with an undesirable course of SDQ-DP. These findings might be helpful for better psychoeducation, counselling and monitoring in clinical cases and public health.

Worth a second look: outcomes of patients with initial finding of regular renal tissue in CT-guided renal tumor biopsies.

INTRODUCTION AND OBJECTIVE: Renal tumor biopsy is recommended for histological diagnosis of radiologically indeterminate renal masses, to select patients with small-renal masses for surveillance approaches, before ablative treatments and to confirm metastatic spread of renal cell cancer (RCC), according to the EAU guidelines. We aimed to determine outcomes of patients with suspicious renal masses with initial finding of regular renal tissue in renal tumor biopsies. METHODS: Retrospective database analysis of 101 patients undergoing CT-guided-, percutaneous renal tumor biopsies in local anesthesia. RESULTS: In 23/101 patients, histopathologic evaluation of the biopsies showed regular renal tissue. Of these, two patients underwent simultaneous radiofrequency ablation (RFA), 2/23 underwent radical nephrectomy, despite negative biopsy because of radiological suspicious aspect. Overall, 12 patients underwent a second set of biopsies due to persistent clinical suspicion. Of these, five were diagnosed with RCC: three clear cell renal cell carcinoma (ccRCC) and two papillary renal cell carcinoma (pRCC). Benign tumours were found in two patients. A lymphoma was found in two patients. In 3/12 patients, also the second set of biopsies showed regular renal tissue. CONCLUSION: An unsuspicious histology in CT-guided renal tumor biopsy does not preclude patients with suspicious renal masses from being diagnosed with malignancies.

Postoperative imaging of orthopaedic hardware in the hand and wrist: is there an added value for tomosynthesis?

AIM: To prospectively investigate digital tomosynthesis (DTS) as an alternative to digital radiography (DR) for postoperative imaging of orthopaedic hardware after trauma or arthrodesis in the hand and wrist. MATERIALS AND METHODS: Thirty-six consecutive patients (12 female, median age 36 years, range 19-86 years) were included in this institutional review board approved clinical trial. Imaging was performed with DTS in dorso-palmar projection and DR was performed in dorso-palmar, lateral, and oblique views. Images were evaluated by two independent radiologists for qualitative and diagnosis-related imaging parameters using a four-point Likert scale (1=excellent, 4not diagnostic) and nominal scale. Interobserver agreement between the two readers was assessed with Cohen's kappa (k). Differences between DTS and CR were tested with Wilcoxon's signed-rank test. A p-value <0.05 was considered statistically significant. RESULTS: Regarding image quality, interobserver agreement was higher for DTS compared to DR, especially for fracture-related parameters (delineation osteosynthesis material [OSM]: KDTS0.96 versus KDR0.45; delineation fracture margins: KDTS0.78 versus KDR0.35). Delineation of fracture margins and delineation of adjacent joint spaces scored significant better for DTS compared to DR (delineation fracture margins: DTS1.54, DR2.28, p0.001; delineation adjacent joint spaces: DTS1.31, DR2.24, p0.001). Regarding diagnosis-related findings, interobserver agreement was almost equal. DTS showed a significant higher sharpness of fracture margins (DTS1.94, DR2.33, p0.04). Mean dose area product (DAP) for DTS was significant higher compared to DR (mean DR0.219 Gy·cm2, mean DTS0.903 Gy·cm2, p0.001). CONCLUSION: Fracture healing is more visible and interobserver agreement is higher for DTS compared to DR in the postoperative assessment of orthopaedic hardware in the hand and wrist.