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Angesichts einer migrationsbedingt vielfältiger werdenden Gesellschaft sind Heranwachsende nicht selten von Vorbehalten gegenüber Geflüchteten betroffen, wobei auch von der Medienberichterstattung Einflüsse ausgehen. Der Abbau von Vorurteilen, als wesentlicher Aspekt interkultureller Kompetenzentwicklung, kann durch die Gestaltung medialer Beiträge in Form sogenannter Critical Incidents unterstützt werden. Diese adressiert nicht nur die Auseinandersetzung mit vorurteilsgeprägten Sichtweisen, sondern auch die aus medienpädagogischer Perspektive geforderte Partizipation am Diskurs zu Flucht und Migration. Im Mittelpunkt dieses Beitrags steht deshalb eine qualitative Untersuchung von Stop-Motion-Videos, die in interkultureller Zusammenarbeit von Jugendlichen auf der Basis von Critical Incidents als Missverständnisse und Konflikte zwischen Deutschen und Geflüchteten produziert wurden. Ausgehend von interkulturell-kommunikativen und medienpädagogischen Grundlagen wird anschliessend die Gestaltung medialer Beiträge mit der inhaltlichen Ausrichtung auf Critical Incidents fokussiert. Auf der Basis eines qualitativen Untersuchungsdesigns werden die Stop-Motion-Videos hinsichtlich wesentlicher Aspekte der Kommunikationssituation, formaler Medienmerkmale sowie inszenierter verhaltensbezogener Aspekte interkultureller Kompetenz ausgewertet. Während die Ergebnisse zu Aspekten der Kommunikationssituation darauf verweisen, dass die dargestellten Begegnungssituationen sehr komplex und vielschichtig sind, zeigt die Untersuchung der Medienmerkmale u. a., dass die Kommunikation zwischen den Beteiligten hauptsächlich visuell in Form schriftlicher Texte umgesetzt wurde. Aus den Ergebnissen zur Inszenierung der behavioralen Dimension interkultureller Kompetenz geht beispielsweise hervor, dass in allen Videos offene Selbstauskunft als Möglichkeit gewählt wird, interkulturelle Missverständnisse aufzulösen. Abschliessend wird auf die Bedeutsamkeit verwiesen, im Rahmen einer gestaltungsorientierten Bildungsforschung weitere Studien unter Berücksichtigung interkulturell-kommunikativer und medienpädagogischer Perspektiven zu realisieren.

Der vorliegende Beitrag befasst sich mit der Anwendung von Mixed Methods im Kontext gestaltungsorientierter Bildungsforschung. Hierfür werden zunächst grundlegende Charakteristika, Motive und Designformen von Mixed Methods erarbeitet, bevor anschließend verschiedene Möglichkeiten der Integration vorgestellt werden. Daraufhin folgt eine Untersuchung exemplarisch ausgewählte Ansätze gestaltungsorientierter Bildungsforschung hinsichtlich der systematischen Kombination qualitativer und quantitativer Methoden. Anhand eines Forschungsprojekts zur Förderung von Medienkritikfähigkeit bei Jugendlichen im Kontext zeitgenössischer Propaganda, das auf Basis der praxis- und theorienorientierten Entwicklung und Evaluation von Konzepten unterrichtlichen Handelns (vgl. Tulodziecki, Grafe, und Herzig 2013) entwickelt wurde, soll schlussendlich die konkrete Umsetzung von Mixed-Methods-Designs sowie die Verwendung von Integrationsstrategien demonstriert werden.

In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the "meningitis/encephalitis panel" (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP's efficacy in paediatric patients.Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children's Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics.Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [-1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397).The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients.

To investigate the response of the immune system (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.531 vaccinees, recruited from healthcare professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via interferon-γ (IFN-γ) release assay, and antibodies against different epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (S1 and NCP) were detected via ELISA and surrogate neutralization assay. Results were correlated with influencing factors such as age, sex, prior infection, vaccine received (BNT162b2 or mRNA-1273), and immunosuppression. Furthermore, antinuclear antibodies (ANAs) were measured to screen for autoimmune responses following vaccination with an mRNA vaccine.No markers of immunity against SARS-CoV-2 were found before the first vaccination. Two weeks after it, specific responses against SARS-CoV-2 were already measurable (median ± median absolute deviation (MAD): anti-S1 IgG 195.5 ± 172.7 BAU/mL; IgA 6.7 ± 4.9 OD; surrogate neutralization 39 ± 23.7%), and were significantly increased two weeks after the second dose (anti-S1 IgG 3744 ± 2571.4 BAU/mL; IgA 12 ± 0 OD; surrogate neutralization 100 ± 0%, IFN-γ 1897.2 ± 886.7 mIU/mL). Responses were stronger for younger participants (this difference decreasing after the second dose). Further influences were previous infection with SARS-CoV-2 (causing significantly stronger responses after the first dose compared to unexposed individuals (p ≤ 0.0001)) and the vaccine received (significantly stronger reactions for recipients of mRNA-1273 after both doses, p 0.05-0.0001). Some forms of immunosuppression significantly impeded the immune response to the vaccination (with no observable immune response in three immunosuppressed participants). There was no significant induction of ANAs by the vaccination (no change in qualitative ANA results (p 0.2592) nor ANA titres (p 0.08) from pre-to post-vaccination.Both vaccines elicit strong and specific immune responses against SARS-CoV-2 which become detectable one week (T-cell response) or two weeks (B-cell response) after the first dose.

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Background Previous research has supported the utility of the Double ABCX model of family adaptation for parents in various diseases. Nonetheless, it remains unclear how raising a child with rare congenital surgical diseases impacts the mental health of both mothers and fathers. Methods The potential predictors of maternal and paternal mental health in a German sample of 210 parents of children with rare congenital surgical diseases were investigated. Parents were investigated cross-sectionally utilizing standardized psychometric questionnaires that assessed factors attributed to parental adaptation within the Double ABCX model. Results Stressor pile-up, family functioning, perceived stress, and mental health were positively associated with mothers and fathers. However, further analyses revealed that family functioning, social support, and perceived stress fully mediated the positive association between stressor pile-up and mental health in mothers, but not fathers. Conclusion Our findings suggest that parental adaptation to a rare congenital surgical disease in their children may be improved by increased intra- and extrafamilial resources and decreased perceived family-related stress in mothers, but not fathers. Our results may help to identify gender-specific factors that may guide clinicians and future interventions.

Background The rational use of antibiotics is of great importance in health care. In primary care, acute respiratory infections are the most common cause of inappropriate antibiotic prescribing. Since existing studies aiming to optimize antibiotic use are usually based on the voluntary participation of physicians, general practitioners (GPs) with inappropriate prescribing behavior are underrepresented. For the first time in Germany, the ElektRA study will assess and compare the effects of three interventions on antibiotic prescribing rates for respiratory and urinary tract infections among high prescribers in primary care. Method ElektRA is a 4-arm cluster-randomized controlled trial among German GPs in nine regional Associations of Statutory Health Insurance Physicians. On their behalf, the Central Research Institute of Ambulatory Health Care in Germany (Zi) analyses all outpatient claims and prescription data. Based on this database, high antibiotic prescribing GPs are identified and randomized into four groups: a control group (N=2000) and three intervention arms. We test social norm feedback on antibiotic prescribing (N=2000), social norm feedback plus online training on rational prescribing practice and communication strategies (N=2000), and social norm feedback plus online peer-moderated training on rational antibiotic prescribing, communication strategies, and sustainable behavior change (N=1250). The primary outcome is the overall rate of antibiotic prescriptions. Outcomes are measured before intervention (T0, October 2020–September 2022) and over a period of 15 months (T1, October 2022 to December 2023) after randomization. Discussion The aim of the study is to implement individualized, low-threshold interventions to reduce antibiotic prescribing among high prescribers in primary care. If successful, a change in behavior among otherwise difficult-to-reach high prescribers will directly improve patient care. The increase in quality of care will ideally be achieved both in terms of the quantity of antibiotics used as well as the kind of substances prescribed. Also, if effective strategies for high prescribers are identified through this study, they can be applied not only to the antibiotics addressed in this study, but also to other areas of prescription management. Trial registration Current Controlled Trials ISRCTN95468513.

In medical research, continuous variables are often categorised into two or more groups before being included in the analysis; this practice often comes with a cost, such as loss of power in analysis, less reliable estimates, and can often leave residual confounding in the results. In this research report, we show this by way of estimates from a regression analysis looking at the association between acute kidney injury and post-operative mortality in a sample of 194 neonates who underwent the Norwood operation. Two models were developed, one using a continuous measure of renal function as the main explanatory variable and second using a categorised version of the same variable. A continuous measure of renal function is more likely to yield reliable estimates and also maintains more statistical power in the analysis to detect a relation between the exposure and outcome. It also reveals the true biological relationship between the exposure and outcome. Categorising a continuous variable may not only miss an important message, it can also get it wrong. Additionally, given a non-linear relationship is commonly encountered between the exposure and outcome variable, investigators are advised to retain a predictor with a linear term only when supported by data. All of this is particularly important in small data sets which account for the majority of clinical research studies.

IntroductionUlcerative colitis (UC) and irritable bowel syndrome (IBS) are distressing chronic diseases associated with abdominal pain and altered bowel habits of unknown aetiology. Results from previous studies indicate that, across both diseases, increased levels of illness-related anxiety and dysfunctional symptom expectations contribute to symptom persistence. Thus, comparing both disorders with regard to common and disease-specific factors in the persistence and modification of gastrointestinal symptoms seems justified. Our primary hypothesis is that persistent gastrointestinal symptoms in UC and IBS can be improved by modifying dysfunctional symptom expectations and illness-related anxiety using expectation management strategies.Methods and analysisTo assess the extent to which persistent somatic symptoms are modifiable in adult patients with UC and IBS, we will conduct an observer-blinded, three-arm randomised controlled trial. A total of 117 patients with UC and 117 patients with IBS will be randomised into three groups of equal size: targeted expectation management aiming to reduce illness-related anxiety and dysfunctional symptom expectations in addition to standard care (SC, intervention 1), non-specific supportive treatment in addition to SC (intervention 2) or SC only (control). Both active intervention groups will comprise three individual online consultation sessions and a booster session after 3 months. The primary outcome is baseline to postinterventional change in gastrointestinal symptom severity.Ethics and disseminationThe study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10198-BO-ff). The study will shed light onto the efficacy and mechanisms of action of a targeted expectation management intervention for persistent gastrointestinal symptoms in patients with UC and IBS. Furthermore, the detailed analysis of the complex biopsychosocial mechanisms will allow the further advancement of aetiological models and according evidence-based intervention strategies.Trial registration numberISRCTN30800023.

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis. In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as "preclinical-" and "subclinical AKI" have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab.A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound.Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab.Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb.This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.

IntroductionLiving in an area with no or deficient structures for trans health care is disadvantageous for trans people. By providing an internet-based health care programme, i²TransHealth aims at reducing structural disadvantages for trans people living in areas lacking specialised care. The e-health intervention consists of video consultations and a 1:1 chat with a study therapist. Additionally, the i²TransHealth network cooperates with physicians, who especially offer crisis intervention close to the participants’ place of residence. The aim of this study is to evaluate the (cost-)effectiveness of the internet-based health care programme for trans people compared with a control (waiting) group. The following research questions will be examined with a sample of 163 trans people: Does a 4-month treatment with the i²TransHealth internet-based health care programme improve patient-reported health-outcomes? Is i²TransHealth cost-effective compared with standard care from a societal or health care payers’ perspective? Does the participation in and support by i²TransHealth lead to an increase of trans-related expertise in the physician network?Methods and analysisIn a randomised controlled trial, the outcomes of an internet-based health care programme for trans people will be investigated. In the intervention group, participants are invited to use i²TransHealth for 4 months. Participants allocated to the control group will be able to start with their transition-related care after 4 months of study participation. The primary outcome measure is defined as the reduction of psychosomatic symptoms, as assessed by the Brief Symptom Inventory-18, 4 months after using the i²TransHealth programme. Participants in both groups will undergo an assessment at baseline and 4 months after using i²TransHealth.Ethics and disseminationPositive ethical approval was obtained from the Hamburg Medical Association (PV7131). The results will be disseminated to service users and their families via media, to health care professionals via professional training and meetings and to researchers via conferences and publications.Trial registration numberNCT04290286.Protocol version22 December 2021 (V.1.0)

IntroductionPersistent somatic symptoms (PSS) are highly prevalent in all areas of medicine; they are disabling for patients and costly for society. The subjective symptom burden often correlates poorly with the underlying disease severity, and patients’ needs for effective treatment are far from being met. Initial evidence indicates that, in addition to disease-specific pathophysiological processes, psychological factors such as expectations, somatosensory amplification and prior illness experiences contribute to symptom persistence in functional as well as in somatic diseases. However, prospective studies investigating the transition from acute to chronic somatic symptoms, integrating pathophysiological, psychological and social factors, are scarce. A better understanding of the multifactorial mechanisms of symptom persistence is crucial for developing targeted mechanism-based interventions for effective prevention and treatment of PSS. Thus, the overall aim of the interdisciplinary SOMACROSS research unit is to identify generic and disease-specific risk factors and aetiological mechanisms of symptom persistence across a range of diseases.Methods and analysisSeven projects will investigate risk factors and mechanisms of symptom persistence in a total of 3916 patients across 10 medical conditions. All study designs are prospective and share common assessment points, core instruments and outcome variables to allow comparison and validation of results across projects and conditions. Research will focus on the identification of generic and disease-specific mechanisms associated with unfavourable symptom course. The development of a multivariate prediction model will facilitate the understanding of the course of PSS across diseases.Ethics and disseminationAll individual SOMACROSS studies were approved by the ethics committees of the Medical Chambers Hamburg and Münster, Germany. Findings will be disseminated through peer-reviewed publications, scientific conferences and the involvement of relevant stakeholders, patients and the lay public. This interdisciplinary research unit will fundamentally contribute to earlier recognition of patients at risk, and to the development of prevention and tailored treatment concepts for PSS.

Background COVID-19 has affected our society at large, particularly vulnerable groups, such as children suffering from rare diseases and their parents. However, the psychosocial influences of COVID-19 on these have yet to be investigated. As such, the study’s goal was to evaluate the health-related quality of life (HRQoL), quality of life (QoL), and mental health of children with rare congenital surgical diseases and their parents during the COVID-19 pandemic and lockdown measures. Methods A survey of n = 210 parents of children with rare congenital surgical diseases and a control group of n = 88 parents of children without rare diseases was conducted cross-sectionally between April 2020 to April 2021. Data on HRQoL, QoL, and mental health was collected using standardized psychometric questionnaires for children and parents presenting to the pediatric surgery department at a university hospital. Results Mothers of children with rare pediatric surgical diseases showed significantly lower QoL and significantly higher impairment in mental health than a control group and norm data. For fathers, this was solely the case for their QoL. Children’s parent-reported HRQoL and mental health were partially impaired. Social and disease-specific risk factors of the respective outcomes in affected families were identified through regression analysis models. Conclusion Parents of children with rare diseases report severe psychosocial impairment regarding themselves and their children during the COVID-19 pandemic. Therefore, affected families should receive attention and supportive care in the form of a family-center approach to alleviate the additional burden of the COVID-19 pandemic.

To examine the state of B-cell immunity 6 months after the second vaccination against SARS-CoV-2 in comparison to the state observed 2 weeks after vaccination.Sera of 439 participants, whose immune responses to two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) were previously characterized, was examined for anti-S1 IgG and IgA, anti-NCP IgG and neutralizing antibodies (nAb), and antinuclear antibodies (ANA).Levels of all examined markers decreased significantly from 2 weeks to 6 months after second vaccination (anti-S1 IgG: 3744 ± 2571.4 vs. 253 ± 144 binding antibody units (BAU)/mL; anti-S1 IgA: 12 ± 0 vs. 1.98 ± 1.75 optical density (OD) ratio; nAb: 100% ± 0% vs. 82% ± 19.3%), the vast majority of participants retaining reactive levels of anti-S1 IgG (436/439) and anti-S1 IgA (334/439) at 6 months. Immune responses were stronger for mRNA-1273 compared with BNT162b2 (anti-S1 IgG: 429 ± 289 vs. 243 ± 143 BAU/mL; anti-S1 IgA: 5.38 ± 3.91 vs. 1.89 ± 1.53 OD ratio; nAb: 90.5% ± 12.6% vs. 81% ± 19.3%). There was no meaningful influence of sex and age on the examined markers. There was a strong correlation between anti-S1 IgG and the surrogate neutralization assay (rho = 0.91, p0.0001), but not for for IgA and the surrogate neutralization assay (rho = 0.52, p0.0001). There was a ceiling effect for the association between anti-S1 IgG titres and the inhibition of binding between S1 and ACE2. ANA prevalence was unchanged from 2 weeks to 6 months after the second vaccination (87/498 vs. 77/435), as were the median ANA titres (1:160 vs. 1:160).Although the clinical consequences of decreasing anti-SARS-CoV-2 antibody titres cannot be estimated with certainty, a lowered degree of clinical protection against SARS-CoV-2 is possible. Persistently stronger responses to mRNA-1273 suggest that it might confer greater protection than BNT162b2, even 6 months after the second vaccination. Neither examined vaccinations induced ANA within the examined time frame.

“Our aim as scientists is objective truth; more truth, more interesting truth, more intelligible truth. We cannot reasonably aim at certainty.” Karl Popper (from In Search of a Better World , 1995). The enormous success of endovascular thrombectomy (EVT) for stroke treatment has engendered increasing interest from the medical scientific community as well as industry. New companies have been founded and substantial capital raised and used for the development of new technologies to further improve patient outcomes in ischemic stroke and in other conditions in the neurointerventional realm. These new technologies need to be developed and subsequently tested for their performance and safety in patient care. Prospective single-arm studies are a reasonable standard for the early phase of a device evaluation. For such studies, the comparator and its point estimate are typically based on a meta-analysis of historical data. Other study designs such as virtual comparator groups have been tested as well.1 Recently, more randomized controlled trials (RCTs) have been initiated relatively early following encouraging observations in multiple case series. The numerous RCTs that were started in the field of middle meningeal artery embolization are positive examples of this.2–5 This development indicates a trend towards better neurointerventional study quality that is also observed in RCTs whose purpose is the head-to-head comparison of different devices.6 There are two common hypothesis scenarios for testing the primary efficacy endpoint (eg, clinical outcome after 3 months). First, testing for superiority regarding efficacy is chosen if the new therapy has the potential to be more costly or risky. Second, testing for non-inferiority is conducted if the new therapy is comparable to the previous standard therapy but might offer advantages in other areas …

Background The accurate diagnosis of a disease is a prerequisite for its appropriate treatment. How well a medical test is able to correctly identify or rule out a target disease can be assessed by diagnostic accuracy studies. Methods The main statistical parameters that are derived from diagnostic accuracy studies, and their proper interpretation, will be presented here in the light of publications retrieved by a selective literature search, supplemented by the authors' own experience. Aspects of study planning and the analysis of complex studies on diagnostic tests will also be discussed. Results In the usual case, the findings of a diagnostic accuracy study are presented in a 2 × 2 contingency table containing the number of true-positive, true-negative, false-positive, and true-positive test results. This information allows the calculation of various statistical parameters, of which the most important are the two pairs sensitivity/specificity and positive/negative predictive value. All of these parameters are quotients, with the number of true positive (resp. true negative) test results in the numerator; the denominator is, in the first pair, the total number of ill (resp. healthy) patients, and in the second pair, the total number of patients with a positive (resp. negative) test. The predictive values are the parameters of greatest interest to physicians and patients, but their main disadvantage is that they can easily be misinterpreted. We will also present the receiver operating characteristic (ROC) curve and the area under the curve (AUC) as additional important measures for the assessment of diagnostic tests. Further topics are discussed in the supplementary materials. Conclusion The statistical parameters used to assess diagnostic tests are primarily based on 2 × 2 contingency tables. These parameters must be interpreted with care in order to draw correct conclusions for use in medical practice.

Purpose Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured “Enhanced Recovery after Surgery (ERAS)” program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer. Methods 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital. Results Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p p = 0.011), and length of hospital stay (ERAS: 11 (6–23) vs pre-ERAS: 13 (6–50) days; p p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group. Conclusion The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated.

Onychomycosis is common. Diagnosis can be confirmed by various methods; a commonly used method is the histological examination of nail clippings. A deep learning system was developed and its diagnostic accuracy compared with that of human experts. A dataset with annotations for fungal elements was used to train an artificial intelligence (AI) model. In a second dataset (n=199) the diagnostic accuracy of the AI was compared with that of dermatopathologists. The results show a non-inferiority of the deep learning system to that of analogue diagnosis (non-inferiority margin 5%) with respect to specificity and the area under the receiver operating characteristic curve (AUC). The AI achieved an AUC of 0.981. One limitation of this system is the need for a large number of training images. The AI had difficulty recognizing spores and confused serum or aggregated bacteria with fungal elements. Use of this deep learning system in dermatopathology routine might help to diagnose onychomycosis more efficiently.

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking., peer-reviewed

Objectives To assess the incidence of acute adverse events (AAEs) in gadolinium-enhanced cardiac magnetic resonance (CMR) imaging. Methods Gadolinium-based contrast agent (GBCA)–enhanced CMR data from the multinational, multicenter European Society of Cardiovascular Radiology MRCT Registry was included. AAE severity was classified according to the American College of Radiology Manual on Contrast Media (mild, moderate, severe). Multivariable generalized linear mixed effect models were used to assess the likelihood of AAEs in various GBCA, adjusting for pharmacological stressor, main indications (i.e., suspected or known coronary artery disease or myocarditis), age, sex, and submitting center as a random effect. Results In the study population of 72,839 GBCA-enhanced CMRs, a total of 260 AAEs were reported (0.36%), with a minority of severe AAEs (n = 24, 0.033%). Allergic-like AAEs were less likely than physiologic AAEs (29% versus 71%). Patients without pharmacological stress imaging had a lower AAE rate (0.22%) compared to stress imaging (0.75%), with the highest AAE rates for regadenoson (2.95%). AAE rates also varied by GBCA subtype (overall p

The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant.To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab.This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria.For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy.For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound.A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence.In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant.ClinicalTrials.gov Identifier: NCT04790786.

Methods for standard meta-analysis of diagnostic test accuracy studies are well established and understood. For the more complex case in which studies report test accuracy across multiple thresholds, several approaches have recently been proposed. These are based on similar ideas, but make different assumptions. In this article, we apply four different approaches to data from a recent systematic review in the area of nephrology and compare the results. The four approaches use: a linear mixed effects model, a Bayesian multinomial random effects model, a time-to-event model and a nonparametric model, respectively. In the case study data, the accuracy of neutrophil gelatinase-associated lipocalin for the diagnosis of acute kidney injury was assessed in different scenarios, with sensitivity and specificity estimates available for three thresholds in each primary study. All approaches led to plausible and mostly similar summary results. However, we found considerable differences in results for some scenarios, for example, differences in the area under the receiver operating characteristic curve (AUC) of up to 0.13. The Bayesian approach tended to lead to the highest values of the AUC, and the nonparametric approach tended to produce the lowest values across the different scenarios. Though we recommend using these approaches, our findings motivate the need for a simulation study to explore optimal choice of method in various scenarios.

IntroductionSARS-CoV-2 has disproportionately affected disadvantaged communities across the USA. Risk perceptions for social interactions and essential activities during the COVID-19 pandemic may vary by sociodemographic factors.MethodsWe conducted a nationally representative online survey of 1592 adults in the USA to understand risk perceptions related to transmission of COVID-19 for social (eg, visiting friends) and essential activities (eg, medical visits or returning to work). We assessed relationships for activities using bivariate comparisons and multivariable logistic regression modelling, between responses of safe and unsafe, and participant characteristics. Data were collected and analysed in 2020.ResultsAmong 1592 participants, risk perceptions of unsafe for 13 activities ranged from 29.2% to 73.5%. Large gatherings, indoor dining and visits with elderly relatives had the highest proportion of unsafe responses (>58%), while activities outdoor, accessing healthcare and going to the grocery store had the lowest (ConclusionEvidence-based interventions should be tailored to sociodemographic differences in risk perception, access to information and health behaviours when implementing efforts to control the COVID-19 pandemic.

IntroductionApproximately one out of six patients in primary care suffers from depression, which often remains undetected. Evidence regarding the efficacy of depression screening in primary care, however, is inconsistent. A previous single-centre randomised controlled trial (RCT) in cardiac patients, the DEPSCREEN-INFO trial, provided the first evidence that written feedback to patients following a positive depression screening reduces depression severity and leads to more comprehensive patient engagement in mental healthcare. To amplify these effects, the feedback should be tailored according to patients’ needs and preferences. The GET.FEEDBACK.GP RCT will test the efficacy of this patient-targeted feedback intervention in primary care.Methods and analysisThe multicentre three-arm GET.FEEDBACK.GP RCT aims to recruit a total of 1074 primary care patients from North, East and South Germany. Patients will be screened for depression using the Patient Health Questionnaire-9 (PHQ-9). In the case of a positive depression screening result (PHQ-9 score ≥10), the participant will be randomised into one of three groups to either receive (a) patient-targeted and general practitioner (GP)-targeted feedback regarding the depression screening results, (b) only GP-targeted feedback or (c) no feedback. Patients will be followed over a period of 12 months. The primary outcome is depression severity (PHQ-9) 6 months after screening. Secondary outcomes include patient engagement in mental healthcare, professional depression care and cost-effectiveness. According to a statistical analysis plan, the primary endpoint of all randomised patients will be analysed regarding the intention-to-treat principle.Ethics and disseminationThe Ethics Committee of the Hamburg Medical Association approved the study. A clinical trial company will ensure data safety, monitoring and supervision. The multicentre GET.FEEDBACK.GP RCT is the first trial in primary care that tests the efficacy of a patient-targeted feedback intervention as an adjunct to depression screening. Its results have the potential to influence future depression guidelines and will be disseminated in scientific as well as patient-friendly language.Trial registration numberNCT03988985.

IntroductionHealthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care.Methods and analysisThe trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions.Ethics and disseminationEthical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications.Trial registration number and registry nameClinicalTrials.gov (NCT03459664), RECOVERProtocol version19 March 2020 (V.3.0)

Immunotherapeutic strategies are increasingly important in neuro-oncology, and the elucidation of escape mechanisms that lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing WT and Pd-1(–/–) mice survived significantly longer than immunodeficient Pfp(–/–) Rag2(–/–) mice. While tumors in Pfp(–/–) Rag2(–/–) mice were highly polyclonal, immunoedited tumors in WT and Pd-1(–/–) mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in WT mice were distinguished by an IFN-γ–mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even more strongly to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.

The purpose of this study was to evaluate and classify causes for anterior cruciate ligament (ACL) reconstruction failure. It was hypothesized that specific technical and biological reconstruction aspects would differ when comparing traumatic and non-traumatic ACL reconstruction failures. One hundred and forty-seven consecutive patients who experienced ACL reconstruction failure and underwent revision between 2009 and 2014 were analyzed. Based on a systematic failure analysis, including evaluation of technical information on primary ACL reconstruction and radiological assessment of tunnel positions, causes were classified into traumatic and non-traumatic mechanisms of failure; non-traumatic mechanisms were further sub-divided into technical and biologic causes. Spearman’s rank correlation coefficient and chi-squared tests were performed to determine differences between groups based on various factors including graft choice, fixation technique, technique of femoral tunnel positioning, tunnel malpositioning, and time to revision. Non-traumatic, i.e., technical, and traumatic mechanisms of ACL reconstruction failure were found in 64.5 and 29.1% of patients, respectively. Biological failure was found only in 6.4% of patients. Non-anatomical femoral tunnel positioning was found the most common cause (83.1%) for technical reconstruction failure followed by non-anatomical tibial tunnel positioning (45.1%). There were strong correlations between non-traumatic technical failure and femoral tunnel malpositioning, transtibial femoral tunnel drilling techniques, femoral transfixation techniques as well as earlier graft failure (p

Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding site suggested that Gln756, an amino acid that rarely occurs at the GK+2 position, offered opportunities for achieving kinase selectivity for ASK1 which was applied to the design of a parallel medicinal chemistry library that afforded inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A focused optimization strategy utilizing structure-based design resulted in the identification of ASK1 inhibitors with low nanomolar potency in a cellular assay, high selectivity when tested against kinase and broad pharmacology screening panels, and attractive physicochemical properties. The compounds we describe are attractive tool compounds to inform the therapeutic potential of ASK1 inhibition.

GET.FEEDBACK.GP 1 is a multicenter randomized controlled trial testing the efficacy of patient-oriented depression feedback in primary care. This paper describes the complex methods and procedures of the trial. The primary outcome is depression severity six months after feedback, and we vary who is the target of the feedback as follows: no one receives feedback, only general practitioners receive feedback, and both patients and general practitioners receive feedback. The procedure includes a baseline assessment in primary care practices and three telephone follow-up interviews after one, six, and twelve months. The patients completed a baseline assessment, which determined their depression severity. Those with at least a moderate depression severity (PHQ-95 ≥ 10) were randomly allocated to three groups stratified by depression severity. A standardized mean difference of d = 0.25 with power 1 - β = 0.80 required a total sample size of N = 699. The patients provided responses regarding the primary and secondary outcomes at follow-up. The extensive planning for GET.FEEDBACK.GP involved experts from diverse medical specialties and external corporations. Of particular importance were (a) blinding in the study inclusion and random assignment with data capture software, (b) representative and unbiased patient selection in practice waiting rooms, (c) a data management and safety plan supplied by a specialized trial center, and (d) the use of participant pseudonyms supplied by a specialized service (Mainzelliste). The data collection started in July 2019 and will continue until June 2022. Five university study centers in Germany are participating in the trial.

Key Clinical Message We demonstrate feasibility and safety of Electrochemotherapy for treatment of a prostate cancer (PCa) with infiltration of the urethral sphincter. The patient remained continent and potent, toxicity was low, and 6 months of follow‐up showed no cancer activity. We conclude that Electrochemotherapy should be further evaluated as treatment strategy for locally advanced PCa.

Magnetic resonance imaging (MRI) is regarded as a non-harming and non-invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes. In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by γH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures. Both cohorts showed a significant increase in the γH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant. Based on our study, γH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells. • No evidence for DNA double-strand breaks after cardiac MRI. • Prospective study underlines safe use of MRI with regard to DNA damage. • Controlled trial involving both genders investigating DNA DSBs after 3-T MRI.

Key Clinical Message The combination of Irreversible Electroporation and Electrochemotherapy (IRECT) was well tolerated, safe, and had antitumor activity in this case study of a patient with lymph node metastases from gastric cancer. We therefore recommend the consideration of further clinical studies to investigate the treatment of cancerous tissue with IRECT.

During the operation of gas storage caverns in rock salt mass the internal pressure changes during filling and withdrawal phases. Additionally temperature variations occur versus operation time. During withdrawal phases the temperature decreases which can lead to stress states in tensile regions at the cavern wall. Because the tensile strength of rock salt is relatively low compared to its compressive strength it is likely that tensile stresses lead to discrete fractures orthogonal to the direction of the tensile stresses. If fractures of this kind are created – whether vertical or horizontal – the gas will penetrate into the fracture at the relevant pressure and further extend the length of the fractures under certain circumstances. There are currently no theoretical approaches describing the manner in which the fractures might propagate into the not by temperature changes influenced rock salt mass during repeated cyclic pressure changes. This aspect is topic of prospective research. Salt caverns cannot be entered but only explored by sonar measurements, with which it is not possible to detect tensile fractures at the cavern wall. Within this paper examples from mining configurations will be shown where temperature changes lead to tensile fractures in the surrounding rock salt. These fractures have been well mapped while the temperature development is well documented. The paper deals with recalculations under consideration of different salt properties of the temperature distributions and the resulting stress state in the surrounding rock salt mass. The stress calculation results and the consequences for the dimensioning of natural gas caverns are going to be discussed and assessed.

The purpose of this study was to map the supervision of European trainees in clinical microbiology and infectious diseases during their training. An international cross-sectional questionnaire survey of 38 questions was distributed among trainees and recently graduated medical specialists from European countries. Descriptive analyses were performed on both the total group of respondents and regionally. In total, 393 respondents from 37 different countries were included. The median of overall satisfaction with the supervisor was 4 (interquartile range 3-4) on a Likert scale (range 1, not satisfied at all-5, completely satisfied). Overall, merely 34% of respondents received constructive feedback from their supervisor on a regularly basis, 36% could evaluate their own supervisor, and just 63% were evaluated on their skills using a written plan. Fifty-two percent did not receive the opportunity to do a part of the specialty training abroad and 63% received support from their supervisors to be involved in research projects or publishing papers. A considerable proportion of trainees, mainly in Southern and Eastern European regions, felt that they did not receive sufficient supervision. This information may be useful in the pursuit of harmonizing the quality of training, achieving a common curriculum, and identifying robust and objective criteria to coach and evaluate trainees in a proper way.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disorder that leads to progressive paralysis of skeletal muscles and death by respiratory failure. There is increasing evidence that ALS is at least in part an axonopathy and that mechanisms regulating axonal degeneration and regeneration might be pathogenetically relevant. Semaphorin 3A (Sema3A) is an axon guidance protein; it acts as an axon repellent and prevents axonal regeneration. Increased Sema3A expression has been described in a mouse model of ALS in which it may contribute to motor neuron degeneration. This study aimed to investigate Sema3A mRNA and protein expression in human CNS tissues. We assessed Sema3A expression using quantitative real-time PCR, in situ hybridization, and immunohistochemistry in motor cortex and spinal cord tissue of 8 ALS patients and 6 controls. We found a consistent increase of Sema3A expression in the motor cortex of ALS patients by all 3 methods. In situ hybridization further confirmed that Sema3A expression was present in motor neurons. These findings indicate that upregulation of Sema3A may contribute to axonal degeneration and failure of regeneration in ALS patients. The inhibition of Sema3A therefore might be a promising future therapeutic option for patients with this disease.

International audience; An experimental chamber (CIME2) has been specially designed to simulate wet atmospheric deposition on limestones used inParis cultural heritage. This instrument is a complementary tool to CIME, a previously developed chamber dedicated to thesimulation of dry atmospheric deposition on monuments and artifacts. The aim of this paper is to describe CIME2 and characterizethe wet deposits produced inside it. Mist (fog), drizzle, and rainfall are differentiated in order to document their ability tosaturate the limestones most currently used in Paris monuments: The Saint-Maximin’s limestone, the Liais of Saint-Maximin, andthe Chauvigny’s limestone are tested. The comparison between normalized and environmental petrophysical data shows that inthe wet deposition simulations, limestones are not systematically water-saturated. Moreover, the realistic experimental conditionschosen favor a more rapid evaporation of the stone water. The quantification of the non-saturation state is a first step that has to betaken into account to improve the geochemical models used to predict the alteration.

International audience; An approach consisting in combining in situ and laboratory experiments is often favoured for investigating the mechanisms involved in the weathering of the materials of the cultural heritage. However, the realistic simulation in the laboratory of the environmental conditions ruling the interactions of atmospheric compounds with materials is a very complex task. The aim of this work is to characterise CIME, a new chamber specially built to simulate the interactions between materials of the cultural heritage and the environment. The originality of this instrument is that beside the usual climatic parameters (temperature, relative humidity, solar radiation) and gaseous pollutants, it also allows the controlled injection of different types of particulate matter such as terrigenous, marine and anthropogenic. Therefore, varied realistic atmospheric environments (marine or urban) can be easily simulated within CIME. In addition to the technical description of CIME, this paper shows the first results obtained by the impact of gaseous pollutants on non-durable glass, bronze and limestone. The first experiments for the deposition of different particles (calcite, clays, soot and halite) are also presented.

Background and purposeThrombectomy has become the standard of care for acute ischaemic stroke due to large vessel occlusion. Aim of this study was to compare the radiological outcomes and time metrics of the various thrombectomy techniques.MethodsIn this retrospective, multicenter study we analysed the data of 450 patients with occlusion of the anterior circulation, treated in five high-volume center from 2013 to 2016. The treatment techniques were divided in three categories: first-pass use of a large-bore aspiration-catheter; first-pass use of a stent-retriever; and primary combined approach (PCA) of an aspiration-catheter and stent-retriever. Primary endpoints were successful reperfusion and groin to reperfusion time. Secondary endpoints were the number of attempts and occurrence of emboli in new territory (ENT). The primary analysis was based on the intention to treat groups (ITT).ResultsThe ITT-analysis showed significantly higher reperfusion rates, with 86% of successful reperfusion in the PCA-group compared with 73% in the aspiration group and 65% in the stent-retriever group. There was no significant difference in groin to reperfusion time regarding the used technique. The secondary analysis showed an impact of the technique on the number of attempts and the occurrence of ENTs. Lowest ENT rates and attempts were reported with the combined approach.ConclusionsThe combined first-pass deployment of a stent-retriever and an aspiration-catheter was the most effective technique for reperfusion of anterior circulation large vessel occlusion. Our results correlate with the latest single-centrere studies, reporting very high reperfusion rates with PCA variations.

The purpose of this study was to examine age-related changes in apparent diffusion coefficient (ADC) during infancy and childhood using routine MRI data. A total of 112 investigations of patients aged 0 to 17.2 years showing a normal degree of myelination and no signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations at 1.5T. ADC maps based on our routinely included axial diffusion weighted sequence were created from the scanner. ADC values were measured in 35 different brain regions investigating normal age-related changes during the maturation of the human brain in infancy and childhood using clinical feasible sequences at 1.5T. The relationship between ADC values and age in infancy and childhood can be described as an exponential function. With increasing age, the ADC values decrease significantly in all brain regions, especially during the first 2 years of life. Except in the peritrigonal white matter, no significant differences were found between both hemispheres. Between 0 and 2 years of life, no significant gender differences were detected. Using ADC maps based on a routinely performed axial diffusion weighted sequence, it was possible first to describe the relationship between ADC values and age in infancy and childhood as exponential function in the whole brain and second to determine normative age-related ADC values in multiple brain regions.