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Competing Interests: Funding Support and Author Disclosures Dr Schwartz has served as a consultant/education for Edwards Lifesciences, Medtronic, Boston Scientific, Abbott, Cordis, Siemens, Philips, and Gore. Dr M. Scherer has served on speakers bureaus for Abbott, Boston Scientific, Edwards Lifesciences, HeartFlow, Philips, and Siemens. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Accurate intraoperative tissue diagnostics could impact on decision making regarding the extent of resection (EOR) during brain tumor surgery. Stimulated Raman histology (SRH) is a label-free optical imaging method that uses different biochemical properties of tissue to generate a hematoxylin-eosin-like image and, in combination with an artificial intelligence-based image classifier, offers the opportunity to obtain rapid intraoperative tissue diagnoses., Objective: The goal of this study was to report on our initial experience with SRH to evaluate its accuracy in comparison to final tissue diagnosis., Materials & Methods: We evaluated 70 consecutive adult cases with brain tumors. We compared results of the three different SRH classifier (diagnostic, molecular and tumor/non-tumor) to the respective final histopathological result. Similarly, we evaluated the isocitrate dehydrogenase (IDH) mutations in 18 patients using SRH. Lastly, we compared SRH results of samples taken from the tumor margins with early postoperative MRI. Prediction accuracy was evaluated by logistic regression and Receiver Operator Curve (ROC) analysis., Results: We included 19 gliomas, 9 metastases, 22 meningiomas and 14 other tumor entities. Regarding accuracy of intraoperative SRH predictions, regression analysis showed an Area Under the Curve (AUC) of 0.77 (95 % C.I. 0.64-0.89, p = 0.0008), suggesting agreement of predictions with final diagnosis. For specific tumor entities, variable accuracies were observed: The highest accuracy was obtained for meningiomas followed by high-grade glioma. IDH mutations were predicted with an AUC of 0.93 (95 % C.I. 0.88-0.98; p < 0.0001). The SRH examination of tissue samples from tumor margins corresponded with postoperative MRI in 4 out of 5 cases., Conclusion: Our initial experience with SRH shows that this novel imaging technique is a promising approach to obtain rapid intraoperative tissue diagnosis to guide surgical decision making based on histology and cell-density. With further refinement of AI-based automated image classification and a better integration into the surgical workflow, prediction accuracy and reliability could be improved., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the context of the evolving landscape of nicotine consumption, the assessment of biomarkers plays a crucial role in understanding the health impact of different product categories. Exhaled breath (EB) emerges as a promising, non-invasive matrix for biomarker analysis, complementary to conventional urine and plasma data. This study explores distinctive EB biomarker profiles among users of combustible cigarettes (CC), heated tobacco products (HTP), electronic cigarettes (EC), smokeless/oral tobacco (OT), and oral/dermal nicotine products (NRT). We have successfully developed and validated a non-targeted GC-TOF-MS method for the analysis of EB samples across the aforementioned product categories. A total of 66 compounds were identified, with significantly elevated levels in at least one study group. The study found that CC users had higher levels of established VOCs associated with smoking, which supports the proof-of-concept of the method. Breathomic analysis identified increased levels of p-cymene and α-pinene in EC users, while HTP users showed potential biomarker candidates like γ-butyrolactone. This study underscores the utility of EB biomarkers for a comprehensive evaluation of diverse nicotine products. The unique advantages offered by EB analysis position it as a valuable tool for understanding the relationship between exposure and health outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Max Scherer reports financial support was provided by Foundation for a Smokefree-World. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The global prevalence of electronic cigarettes, heated tobacco products, and other smokeless alternatives has grown significantly in the last ten years. These products have been suggested as combustion-free alternatives for conventional tobacco products like cigarettes, aiming to reduce the negative health impacts associated with smoking. However, the impact of those products on the health and safety of the general population are still unclear, as the absolute exposure from those products has not been thoroughly studied, yet. In this project, a non-targeted LC-HRMS method was developed comprising four different analytical modes for the investigation of the exposure profile in urine of the product users. The method is characterized by its high sensitivity and reproducibility, as shown during method validation. As a proof of concept, we first applied this method to detect significant differences in biomarkers of exposure (BoEs) between smokers and non-smokers. We observed a total of 171 BoEs significantly elevated in smokers, including several well-known biomarkers of smoke exposure like nicotine and its metabolites, mercapturic acid derivatives, and phenolic compounds. Some of the detected biomarkers are present at low ng/mL concentrations in urine, proving the high sensitivity needed for a holistic exploration of the exposome. Moreover, we were able to identify BoEs that have not been reported previously for smoking, such as 2,6-dimethoxyphenol and 7-methyl-1-naphthol glucuronide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Hamid has received consulting fees from Abbott Structural, 4C Medical, Philips Healthcare, GE, Siemens, Edwards Lifesciences, and vDyne. Dr Aman has received consulting fees from Abbott Structural, Philips Healthcare, Silara Medtech, Revalve, and W.L. Gore. Dr Bae has received consulting fees from Abbott Structural. Dr Scherer has received consulting fees from Abbott Structural, Boston Scientific, Edwards Lifesciences, HeartFlow, and Philips Healthcare. Dr Smith has received consulting fees from Abbott Structural, W.L. Gore, Laminar, and Novo Nordisk; and owns equity in Laminar. Dr Schwartz has received consulting fees and education and research support from Edwards Lifesciences, Abbott Vascular, Medtronic, Boston Scientific, Philips Healthcare, Siemens, and Cordis; and served on scientific advisory boards for Medtronic, Cordis, Boston Scientific, and Edwards Lifesciences. Dr Rinaldi has received consulting fees from Abbott Vascular, Edwards Lifesciences, Boston Scientific, Johnson and Johnson, and Abiomed; and served on scientific advisory boards for Abbott Vascular, Edwards Lifesciences, and Boston Scientific. Dr Singh has received consulting fees from and served on the Speakers Bureau for Abbott Structural Heart; and served as a consultant and on the advisory board for Philips Healthcare. Dr Sorajja has received consulting fees from 4C Medical, Abbott Structural, Anteris, Boston Scientific, Edwards Lifesciences, Evolution Medical, Medtronic, Shifamed, TriFlo, vDyne, and W.L. Gore.

Background: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022., Methods: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration., Results: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B., Conclusions: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Screening for depression in primary care alone is not sufficient to improve clinical outcomes. However, targeted feedback of the screening results to patients might result in beneficial effects. The GET.FEEDBACK.GP trial investigated whether targeted feedback of the depression screening result to patients, in addition to feedback to general practitioners (GPs), leads to greater reductions in depression severity than GP feedback alone or no feedback., Methods: The GET.FEEDBACK.GP trial was an investigator-initiated, multicentre, three-arm, observer-blinded, randomised controlled trial. Depression screening was conducted electronically using the Patient Health Questionnaire-9 (PHQ-9) in 64 GP practices across five regions in Germany while patients were waiting to see their GP. Currently undiagnosed patients (aged ≥18 years) who screened positive for depression (PHQ-9 score ≥10), were proficient in the German language, and had a personal consultation with a GP were randomly assigned (1:1:1) into a group that received no feedback on their depression screening result, a group in which only the GP received feedback, or a group in which both GP and patient received feedback. Randomisation was stratified by treating GP and PHQ-9 depression severity. Trial staff were masked to patient enrolment and study group allocation and GPs were masked to the feedback recieved by the patient. Written feedback, including the screening result and information on depression, was provided to the relevant groups before the consultation. The primary outcome was PHQ-9-measured depression severity at 6 months after randomisation. An intention-to-treat analysis was conducted for patients who had at least one follow-up visit. This study is registered at ClinicalTrials.gov (NCT03988985) and is complete., Findings: Between July 17, 2019, and Jan 31, 2022, 25 279 patients were approached for eligibility screening, 17 150 were excluded, and 8129 patients completed screening, of whom 1030 (12·7%) screened positive for depression. 344 patients were randomly assigned to receive no feedback, 344 were assigned to receive GP-targeted feedback, and 339 were assigned to receive GP-targeted plus patient-targeted feedback. 252 (73%) patients in the no feedback group, 252 (73%) in the GP-targeted feedback group, and 256 (76%) in the GP-targeted and patient-targeted feedback group were included in the analysis of the primary outcome at 6 months, which reflected a follow-up rate of 74%. Gender was reported as female by 637 (62·1%) of 1025 participants, male by 384 (37·5%), and diverse by four (0·4%). 169 (16%) of 1026 patients with available migration data had a migration background. Mean age was 39·5 years (SD 15·2). PHQ-9 scores improved for each group between baseline and 6 months by -4·15 (95% CI -4·99 to -3·30) in the no feedback group, -4·19 (-5·04 to -3·33) in the GP feedback group, and -4·91 (-5·76 to -4·07) in the GP plus patient feedback group, with no significant difference between the three groups (global p=0·13). The difference in PHQ-9 scores when comparing the GP plus patient feedback group with the no feedback group was -0·77 (-1·60 to 0·07, d=-0·16) and when comparing with the GP-only feedback group was -0·73 (-1·56 to 0·11, d=-0·15). No increase in suicidality was observed as an adverse event in either group., Interpretation: Providing targeted feedback to patients and GPs after depression screening does not significantly reduce depression severity compared with GP feedback alone or no feedback. Further research is required to investigate the potential specific effectiveness of depression screening with systematic feedback for selected subgroups., Funding: German Innovation Fund., Translation: For the German translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests BL reports research funding (no personal honoraria) from the German Research Foundation, the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, the European Commission Horizon 2020 Framework Programme, the European Joint Programme for Rare Diseases, the Ministry of Science, Research and Equality of the Free and Hanseatic City of Hamburg, Germany, and the Foundation Psychosomatics of Spinal Diseases, Stuttgart, Germany. He has received remuneration for several scientific book articles from various book publishers and as a committee member from Aarhus University, Denmark. He received travel expenses from the European Association of Psychosomatic Medicine (EAPM) and accommodation and meals from the Societatea de Medicina Biopsyhosociala, Romania, for a presentation at the EAPM Academy at the Conferința Națională de Psihosomatică (Cluj-Napoca, Romania; October, 2023). He was a board member of the EAPM (unpaid) until 2022. MS reports research funding (no personal honoraria) from the German Innovation Committee at the Joint Federal Committee. He is President of the German College of General Practitioners. GM reports research funding (no personal honoraria) from the German Innovation Committee at the Joint Federal Committee. She has received remuneration for a book chapter from Elsevier and for a lecture from the Forum Palliativmedizin. ME reports research funding (no personal honoraria) from the German Innovation Committee at the Joint Federal Committee and the Deutsche Alzheimer Gesellschaft e.V. Selbsthilfe Demenz. She has received remuneration for a scholarly book chapter from Elsevier. AS reports research funding (no personal honoraria) from the German Research Foundation, the German Federal Ministry of Education and Research, and the German Innovation Committee at the Joint Federal Committee. He has received remuneration for a scholarly book chapter from Elsevier. KL reports research funding (no personal honoraria) from the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, and the Technische Universität München, TUM School of Medicine and the Bavarian Ministry for Science and Art, Munich, Germany. CA reports research funding (no personal honoraria) from the German Federal Ministry of Education and Research. SJ reports research funding (no personal honouraria) from the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, the German Federal Ministry of Health, and the AOK Statutory Health Insurance Baden-Württemberg. She has received remuneration for a scholarly book chapter from Thieme and as a member of the Data and Safety Monitoring Board for a study carried out at the Department of Naturopathy (Charité, Berlin, Germany). She is a member of an expert council on health and care of the German Federal Ministry of Health. SZ is President-elect of the International College of Psychosomatic Medicine. He is a member of the editorial board of The Lancet Psychiatry. SS reports research funding (no personal honouraria) from the Central Institute of the Association of Statutory Health Insurance Physicians in Germany (Zentralinstitut für die kassenärztliche Versorgung). He has received remuneration for a book chapter from Thieme. KB-F reports research funding (no personal honoraria) from the German Research Foundation and the German Federal Ministry of Education and Research. CN reports research funding (no personal honoraria) from the German Research Foundation, the German Federal Ministry of Education and Research, the Ministry of Science and Art Baden-Württemberg (Germany), the German Federal Ministry of Health, and the Köhler Research Fund (Germany). He has received remuneration for several scientific book articles from various book publishers. MH reports research funding (no personal honoraria) from the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, and the DAK Gesundheit (Germany; health insurance fund). He has received remuneration for several scientific book articles from various book publishers and consulting fees from the Agency for Quality in Medicine (Berlin, Germany). He has received honoraria for lectures and presentations from the Techniker Krankenkasse (Germany), the Kanton Basel CH, the Polish Institute for Evidence-based Medicine, the Klinik Münsterlingen, and the University of Lübeck (Germany). He has received payment for expert testimony from the Institute of Regional Health Research, University of Southern Denmark. As a member of the Executive Board, he has received congress fees and travel expenses to the 22nd Congress of Health Services Research 2023 from the German Network of Health Services Research, and he has received travel costs from the German Cancer Society to attend their meeting. He was Chief Executive of the German Network for Health Services Research (unpaid), Past President of the German Society of Medical Psychology (unpaid), and previous President of the International Shared Decision Making Society (unpaid). JG reports research funding (no personal honoraria) from the German Research Foundation and the German Federal Ministry of Education and Research. He has received remuneration for a scholarly book from Elsevier. He has received honoraria for lectures and presentations from Lundbeck, Janssen-Ciag, and Boehringer. H-HK reports research funding (no personal honoraria) from the German Research Foundation, the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, the European Commission Horizon 2020 Framework Programme, the European Union, and the Zentralinstitut für die kassenärztliche Versorgung (Germany). AF reports research funding (no personal honoraria) from the German Research Foundation and the German Innovation Committee at the Joint Federal Committee. EV reports research funding (no personal honoraria) from the German Research Foundation and the German Innovation Committee at the Joint Federal Committee. AZ reports research funding (no personal honoraria) from the German Research Foundation and the German Innovation Committee at the Joint Federal Committee. ML is an employee of Oviva, Germany. SK reports research funding (no personal honoraria) from the German Research Foundation and the German Federal Ministry of Education and Research. All other authors report no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Identifying functional biomarkers related to treatment success can aid in expediting therapy optimization, as well as contribute to a better understanding of the neural mechanisms of the treatment-resistant depression (TRD) and subcallosal cingulate deep brain stimulation (SCC-DBS). Magnetoencephalography data were obtained from 16 individuals with SCC-DBS for TRD and 25 healthy subjects. The first objective of the study was to identify region-specific oscillatory modulations that both (i) discriminate individuals with TRD (with SCC-DBS OFF) from healthy controls, and (ii) discriminate TRD treatment responders from non-responders (with SCC-DBS ON). The second objective of this work was to further explore the effects of stimulation intensity and frequency on oscillatory activity in the identified brain regions of interest. Oscillatory power analyses led to the identification of brain regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Broca's area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity. The identified functional network biomarkers implicate modulation of TRD-related activity in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. These electrophysiological biomarkers have the potential to be used as functional proxies for therapy optimization. Additional stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or reducing frequency, which may represent potential avenues of direction in non-responders., Competing Interests: Declaration of competing interest A.M.L. is a consultant to Abbott, Boston Scientific, Medtronic, and Functional Neuromodulation. L.M. has received honoraria and travel funds from Medtronic (unrelated to this work). All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The 2022 incoming fellows' expectations for their robotics training, as well as their perceptions of the utility of the surgical robot, are not well defined., Methods: Cross-sectional survey of 24 AHPBA fellows in 2022, analyzed with descriptive statistics and Spearman's rho., Results: Of 33 current AHPBA fellows, 22 completed the survey (66.7%). Study participants had limited-to-moderate experience with robotics prior to fellowship (mean 2.5 ± SD 1.1; range 1-4). Most participants agreed that robotics influenced their fellowship choice (mean 4.14 ± SD 0.87; range 1-5), would make then more marketable (mean 4.77 ± SD 0.52; range 1-5) and improve job prospects (mean 4.68 ± SD 0.87; range 1-5). Of the study participants, 55% responded that robotics training is "essential" in fellowship, while 64% responded that it is "essential" for their careers. Fellows were only slightly satisfied with overall robotics training within their respective programs (mean 3.44 ± SD 1.17; range 1-5) The majority (73.7%) expect that robotics will comprise <25% of their training. Notably, the majority (75%) have no formal robotics training curriculum., Discussion: This survey identifies potential gaps where robotics training could be improved for future incoming AHPBA fellows., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

2,4,7,9-Tetramethyldec-5-yne-4,7-diol (TMDD) is a non-ionic surfactant commonly used as defoaming agent and numerous other applications. Effluents of wastewater treatment plants have been identified as one of the main sources of TMDD emissions into the environment. Due to its broad application in various fields, TMDD was selected for the development of a biomonitoring method for assessing human exposure within the frame of the cooperation project of the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI) in 2020. This study aimed to identify a urinary metabolite for TMDD by UPLC-Q-Orbitrap-MS which can be used as a biomarker of TMDD exposure. Monohydroxylated TMDD (1-OH-TMDD) was deciphered as the most prominent metabolite of TMDD in humans in a series of in vitro and in vivo experiments. In a next step, a quantitative method for the determination of 1-OH-TMDD was developed and validated. Quantification was achieved by isotope dilution using D 3 -1-OH-TMDD as internal standard. The method is characterized by a simple sample clean-up procedure and an enzymatic hydrolysis of possible metabolite conjugates with ß-glucuronidase. Method validation was performed according to international guidelines for bioanalytical method validation. The method proved its robustness, precision, accuracy and sensitivity for the intended purpose, i.e. the assessment of TMDD exposure in the general population by means of human biomonitoring., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3-17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 μg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 μg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003-2006) on 3-14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007-2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Starting in 2002, regulations and legislative amendments in Germany focused on the non-smoker protection with several measures to reduce exposure to secondhand tobacco smoke (SHS). The present work aimed to evaluate the relationship between polycyclic aromatic hydrocarbons (PAHs) and SHS exposure and to determine to which extent enforced non-smoking regulations and smoking bans affected the exposure of the non-smoking population in Germany since their implementation in the early 2000s until today. For this purpose, cotinine and selected monohydroxylated PAHs (OH-PAHs) were analyzed by means of (UP)LC-MS/MS in 510 24-h-urine samples of the Environmental Specimen Bank collected over a time span of 24 years from 1995 to 2019. Median urinary cotinine levels were found to steadily and significantly decline by 82% from 1995 to 2019. A significant decrease of urinary 3-hydroxybenzo[a]pyrene (19%), 1-OH-pyrene (39%), 1-naphthol (66%), 1- (17%), 2- (25%), and 3-OH-phenanthrene (22%) was also observed throughout the same time span. The decline in urinary levels of cotinine and several OH-PAHs can most likely be attributed to smoking bans and regulations limiting SHS and PAH exposure. This study therefore emphasizes the relevance of human biomonitoring to investigate the exposure of humans to chemicals of concern, assess the effectiveness of regulatory measures, and help policies to enforce provisions to protect public health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nikola Pluym reports financial support was provided by Horizon 2020 European Innovation Council Fast Track to Innovation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Fiber tractography (FT) has become an important noninvasive tool to ensure maximal safe tumor resection in eloquent glioma surgery. Intraoperatively applied FT is still predominantly based on diffusion tensor imaging (DTI). However, reconstruction schemes of high angular resolution diffusion imaging data for high-resolution FT (HRFT) are gaining increasing attention. The aim of this prospective study was to compare the accuracy of sophisticated HRFT models compared with DTI-FT., Methods: Ten patients with eloquent gliomas underwent surgery under awake craniotomy conditions. The localization of acquisition points, representing deteriorations during intraoperative electrostimulation (IOM) and neuropsychological mapping, were documented. The offsets of acquisition points to the respective fiber bundle were calculated. Probabilistic Q-ball imaging (QBI) and constrained spherical deconvolution (CSD)-FT were compared with DTI-FT for the major language-associated fiber bundles (superior longitudinal fasciculus [SLF] II-IV, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus/medial longitudinal fasciculus)., Results: Among 186 offset values, 46% were located closer than 10 mm to the estimated fiber bundle (CSD, 36%; DTI, 40% and QBI, 60%). Moreover, only 10 offsets were further away than 30 mm (5%). Lowest mean minimum offsets (SLF, 7.7 ± 7.9 mm; inferior fronto-occipital fasciculus, 12.7 ± 8.3 mm; inferior longitudinal fasciculus/medial longitudinal fasciculus, 17.7 ± 6.7 mm) were found for QBI, indicating a significant advantage compared with CSD or DTI (P < 0.001), respectively. No significant differences were found between CSD-FT and DTI-FT offsets (P = 0.105), albeit for the compound SLF exclusively (P < 0.001)., Conclusions: Comparing HRFT techniques QBI and CSD with DTI, QBI delivered significantly better results with lowest offsets and good correlation to IOM results. Besides, QBI-FT was feasible for neurosurgical preoperative and intraoperative applications. Our findings suggest that a combined approach of QBI-FT and IOM under awake craniotomy is considerable for best preservation of neurological function in the presented setting. Overall, the implementation of selected HRFT models into neuronavigation systems seems to be a promising tool in glioma surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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-9 5  ≥ 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., (Copyright © 2021. Published by Elsevier Inc.)

Liver transplantation (LT) is a complex operation that most transplant surgeons learn in fellowship. Training varies as there is lack of objective data that can be used to standardize teaching. We performed a retrospective review of our adult LT database with aim of looking at fellow's experience. Using American Society of Transplant Surgery cutoff of, at least 45 LT during fellowship, data for first 45 LT were compared to LT 45-90. Fellow's cases were also clustered in sequential groups of 15 LT and analyzed to estimate the learning curve (LC). Comparison of LT 1-45 with LT 46-90 showed significantly lower total operative times (TOT) (324 vs. 344 min) and warm ischemia times (WIT) (28 vs. 31 min) in the 45-90 group. Rates of biliary complications (23.8% vs. 16.4%) and bile leaks alone (10.3% vs. 5.5%) were significantly higher for first 45 LT. Analysis of fellows experience in sequential clusters of 15 LT showed decreasing TOT, WIT, biliary complications and rates of unplanned return to the OR with progression of fellowship. This study validates the current ASTS requirement of at least 45 LT. LC generated using these data can help individualize training and optimize outcomes through identification of areas in need of improvement., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Metastatic spinal cord compression (MSCC) is a frequent phenomenon in cancer disease, often leading to severe neurological deficits. Especially in patients with complete motor paralysis, regaining the ability to walk is an important treatment goal. Our study, therefore, aimed to assess the neurological outcome of patients with MSCC and complete motor paralysis after decompressive surgery., Methods: Patients with MSCC and complete motor paralysis, surgically treated by decompressive surgery between 2004-2014 at a single institution were retrospectively analyzed. Clinical patient data were collected from medical records. To assess the neurological outcome, Frankel grade (FG) at admission and discharge were compared. Statistical analysis was performed to identify factors associated with an ambulatory status after surgery., Results: Twenty-eight patients were included in this study. The majority of metastases (57 %) were located in the thoracic spine and 75 % showed extraspinal tumor spread. The median interval between loss of ambulation and surgery was 35 h (IQR: 29-70). Posterior circumferential decompression without stabilization was performed in all cases within 24 h of admission. Neurological function improved in 17 patients (63 %) and seven (26 %) even regained the ability to walk following surgery. The rate of complications was low (7%). In statistical analysis, only the Karnofsky Performance Index (KPI) displayed a significant predictive value for an ambulatory status at discharge., Conclusions: Our findings indicate that severely affected MSCC patients with complete motor paralysis might benefit from decompressive surgery even when the loss of ambulation occurred more than 24 h ago., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: There is a lack of studies disentangling whether changes in frailty are associated with subsequent changes in depressive symptoms or vice versa among the oldest old. Consequently, we aimed to disentangle this link., Design: Three waves [follow-up (FU) wave 7 to FU wave 9; n = 423 individuals in the analytical sample] were used from the multicenter prospective cohort study "Needs, Health Service Use, Costs and Health-Related Quality of Life in a Large Sample of Oldest-Old Primary Care Patients (85+)" (AgeQualiDe)., Setting and Participants: Primary care patients aged 85 years and older., Methods: The Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (CFS) was used to quantify frailty, and the Geriatric Depression Scale was used to measure depressive symptoms. It was adjusted for several covariates (sociodemographic and health-related factors) in regression analysis., Results: Multiple linear regressions with first differences showed that initial increases in depressive symptoms (from FU wave 7 to FU wave 8) were associated with subsequent increases in frailty (from FU wave 8 to FU wave 9; β = 0.06, P < .05), whereas initial increases in frailty (from FU wave 7 to FU wave 8) were not associated with subsequent increases in depressive symptoms (from FU wave 8 to FU wave 9)., Conclusions and Implications: The study findings suggest the relevance of increases in depressive symptoms for subsequent increases in frailty. Treatment of depressive symptoms may also be beneficial to postpone frailty., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Benzene and acrylamide are carcinogenic substances contained inter alia in tobacco smoke. The mercapturic acid metabolites of benzene, N-acetyl-S-phenyl-L-cysteine (SPMA), and of acrylamide, N-acetyl-S-(3-amino-3-oxopropyl)-cysteine (AAMA) and N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA), were analysed in 2260 first-morning void urine samples from children and adolescents aged 3-17 years, participating in the population-representative German Environmental Survey on Children and Adolescents, GerES V 2014-2017. SPMA was detected in 98% of the participants with a geometric mean (GM) of 0.097 μg/L urine. Smokers had about 10-fold higher levels of the benzene metabolite SPMA than non-smokers. The sample comprises of 48 self-reported smokers, mainly in the oldest age group (14-17-year-olds). Second-hand smoke exposure, living near busy or very busy roads, and using domestic fuels for heating were additionally associated with higher benzene metabolite levels. SPMA levels in GerES V were lower compared to levels found in other countries, which in part however may reflect different proportions of smokers. The acrylamide metabolites AAMA and GAMA were detected in 100% of the participants with a GM of 72.6 μg/L urine for AAMA and 15.0 μg/L urine for GAMA. Smoking children and adolescents had about 2.5-fold higher AAMA levels than non-smoking ones. The frequency of consumption of french-fried potatoes and potato crisps consumption was also positively associated with urinary AAMA and GAMA levels. Compared to the urinary AAMA and GAMA levels in Germany and other countries, levels in GerES V tended to be higher than in the few studies reported. The urinary levels of the benzene biomarker SPMA, and the acrylamide biomarkers AAMA and GAMA build the basis to derive reference values for the exposure of children and adolescents in Germany. The results reveal options for exposure reduction mainly in personal choices regarding smoking and diet, but also requiring policy to maintain efforts in non-smoking regulations and improving ambient air quality. Providing these results also to the European HBM Initiative HBM4EU will contribute to gain knowledge on the exposure of the European population, the health impact of carcinogens and thus providing support for substantiated exposure assessment., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tobacco smoking contributes to tooth discoloration. Pigmented compounds in the smoke generated by combustion of tobacco can cause discoloration of dental hard tissues. However, aerosols from heated tobacco products cause less discoloration than cigarette smoke (CS) in vitro. The objective of the present study was to optimize a method for extracting the colored chemical compounds deposited on tooth enamel following exposure to total particulate matter (TPM) from CS or a heated tobacco product (Tobacco Heating System [THS] 2.2), analyze the extracts by gas chromatography coupled to time-of-flight mass spectrometry, and identify the key chemicals associated with tooth discoloration. Sixty bovine enamel blocks were exposed for 2 weeks to TPM from CS or THS 2.2 aerosol or to artificial saliva as a control. Brushing without toothpaste and color measurements were performed each week. Noticeable discoloration of enamel was observed following exposure to CS TPM. The discoloration following exposure to THS 2.2 aerosol TPM or artificial saliva was not distinguishable to the eye (ΔE < 3.3). Carbon disulfide was used to extract surface-deposited chemicals. Untargeted analyses were followed by partial least squares correlation against discoloration scores (R 2  = 0.96). Eleven compounds had variable importance in projection scores greater than 2. Discriminant autocorrelation matrix calculation of their mass spectral information identified eight of the eleven compounds as terpenoids. None of the compounds were related to nicotine. Several of these compounds were also detected in THS 2.2 aerosol TPM-exposed enamel, but at lower levels, in line with our findings showing less discoloration. Compared with CS TPM exposure, THS 2.2 aerosol TPM exposure resulted in lower deposition of color-related compounds on enamel surface, consistent with minimal discoloration of dental enamel., Competing Interests: Declaration of Competing Interest Filippo Zanetti, Philippe A. Guy, Adrian Haiduc, Nikolai V. Ivanov, Shoaib Majeed, Julia Hoeng, and Manuel C. Peitsch are employees of Philip Morris International; Walter K. Schlage is a biology consultant paid by Philip Morris International., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To examine differences in the anamnesis in heart failure patients by patient and physician gender., Methods: A factorial experimental design with video vignettes was applied. While the dialog of an initial encounter because of heart failure symptoms was identical in all videos, patients, played by professional actors, differed in terms of gender (male/female), age (55 years/75 years) and Turkish migration history (no/yes). After viewing the video, 128 physicians (50 % female) were asked if they wanted to ask additional questions (yes/no) and if so, what they wanted to ask (open ended). A coding frame was conducted for the open ended question., Results: Compared to male physicians, female physicians more often said they wanted to ask additional questions, especially about psychosocial aspects. Physicians, particularly female physicians, wanted to ask male patients more often about lifestyle aspects compared to female patients., Conclusion: Although the dialog was identical in all videos, some variations in the anamnestic approach regarding physician and patient gender were identified. This is in contrast to current heart failure guidelines that recommend a detailed anamnesis in all patients presenting themselves with heart failure symptoms., Practice Implications: Primary care physicians should reflect how possible gender stereotypes may influence their anamnestic behavior., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cervical spinal cord injury (SCI) is a devastating event with often lifelong disability. In absence of good treatment options, stem cell therapy with among others neural precursor cells (NPCs) has been introduced to improve neuroregeneration. However, due to secondary injury cascades, survival and differentiation of transplanted NPCs remain poor. Physical therapy and rehabilitation are important corner stones for patients with SCI and have shown beneficial effects on neuroregeneration in animal models. In our current study, we therefore assessed the effects of treadmill training on the survival and differentiation of transplanted NPCs after cervical SCI in rats. Our findings suggest that survival of NPCs as well as differentiation into neurons and oligodendrocytes can be significantly increased when stem cell therapy is combined with treadmill training. In addition, myelination, regeneration of descending tracts and tissue sparing can be improved, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: As a result of the resolution of intravoxel fiber crossing, high-resolution fiber tractography (HRFT) provides advantages over conventional diffusion tensor imaging (DTI) for fiber tractography (FT). Nevertheless, neurosurgically applied FT is still predominantly based on DTI. Although the application of HRFT is evolving, there is still a lack of data about which method should be preferred. With this prospectively designed study, we present our initial experience comparing an analytical Q-ball imaging (QBI) approach with constrained spherical deconvolution (CSD) and conventional DTI-FT considering a particularly neurosurgical perspective., Methods: For 18 patients with eloquent gliomas in the dominant hemisphere, probabilistic FT based on QBI, CSD, and DTI was performed for the major components of the language-associated pathways using a routine diffusion-weighted sequence. Quantitative analysis evaluated tract density, tract volume (TV), tract length (TL), number of fibers, and tract surface (TS) of the fiber object., Results: Both HRFT models showed a significantly larger mean TV, TL, and TS compared with DTI (for QBI vs. DTI: TV (P = 0.0000), TL (P = 0.0048), and TS (P = 0.0129); for CSD vs. DTI: TV (P = 0.0000), TL (P = 0.0008), and TS (P = 0.0010)). However, results of QBI versus CSD did not differ significantly for these variables: TV (P = 0.1415), TL (P = 0.2837), and TS (P = 0.3692). Bland-Altman analysis supports these findings, suggesting systematically higher values for TV, TL, and TS with HRFT but no relevant differences of either QBI or CSD. Neither tumor volume nor peritumoral edema influenced FT results., Conclusions: Our quantitative analysis showed no significant differences regarding TV, TL, and TS for the HRFT methods; however, it suggested advantages over DTI-FT in terms of the display of marginal and terminal fibers. In our recently established setting, QBI-FT shows greater potential for integration into the clinical workflow., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A straightforward method for simultaneous determination of 58 aromatic amines (AAs) in clothing textiles is described. Of the tested amines, 22 are known carcinogens and regulated under European law. Further unregulated amines, which are suspected to be carcinogenic or mutagenic, are also expected to occur in textiles. The focus of this study was to obtain a multimethod with regulated and unregulated AAs and to separate different positional isomers of specific amines. To achieve this goal, the HPLC parameters such as column phase chemistry and mobile phase pH were optimized. All other amines were separated with the same conditions evaluated for the positional isomers. The sample preparation was reduced to a minimum in accordance to DIN EN 14362-1. After reductive cleavage and dilution of the extracts, the samples were prepared for LC-MS/MS analysis. Further cleanup of the samples with diatomaceous earth was no longer required with this modified sample preparation. The method was validated by spiking the extracts of blank textiles with the chosen amines. Lower Limits of Quantification (LLOQs) ranged from 1 to 10 mg kg -1 . Excellent linearity from 10 to 500 μg L -1 was obtained with coefficients (r) higher than 0.99 allowing a one-point calibration (300 μg L -1 corresponding to 60 mg kg -1 in textiles) forced through zero for the samples. Recovery ranged from 88 to 116% with intra- and inter-day precision values of 1.8-12.1%. The accuracy of this method was tested by a certified reference material (iis18A03, Institute for laboratory Studies, the Netherlands) and showed excellent recoveries higher than 95%. Finally, the described method was successfully applied on 150 real samples with different textile fibres and colours. Positive results were confirmed by means of the spectral library and with the ion ratios., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS., Methods: In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n = 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm 3 ). In addition, a propensity score matching was executed., Results: All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P = 0.043)., Conclusions: The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in-hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am-7 pm). Transplants with any portion occurring after-hours were more likely to have procurements in-hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short- or long-term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: On the basis of current treatment guidelines, we developed and validated a medication-based chronic disease score (medCDS) and tested its association with all-cause mortality of older outpatients., Study Design and Setting: Considering the most prevalent chronic diseases in the elderly German population, we compiled a list of evidence-based medicines used to treat these disorders. Based on this list, a score (medCDS) was developed to predict mortality using data of a large longitudinal cohort of older outpatients (training sample; MultiCare Cohort Study). By assessing receiver-operating characteristics (ROC) curves, the performance of medCDS was then confirmed in independent cohorts (ESTHER, KORA-Age) of community-dwelling older patients and compared with already existing medication-based scores and a score using selected anatomical-therapeutic-chemical (ATC) codes., Results: The final medCDS score had an ROC area under the curve (AUC) of 0.73 (95% CI 0.70-0.76). In the validation cohorts, its ROC AUCs were 0.79 (0.76-0.82, KORA-Age) and 0.74 (0.71-0.78, ESTHER), which were superior to already existing medication-based scores (RxRisk, CDS) and scores based on pharmacological ATC code subgroups (ATC3) or age and sex alone (Age&Sex)., Conclusions: A new medCDS, which is based on actual treatment standards, predicts mortality of older outpatients significantly better than already existing scores., (Copyright © 2018 Elsevier Inc. All rights reserved.)

7-Hydroxycitronellal is a synthetic fragrance (CAS No. 107-75-5) which is used commonly in cosmetics, washing- and cleaning agents and as flavoring in foods. Due to its broad application in various fields, 7-hydroxycitronellal was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). For this purpose, an ultra performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) based method was developed for the determination of potential biomarkers of 7-hydroxycitronellal (7-HC) in human urine samples. 7-Hydroxycitronellylic acid (7-HCA) turned out to be the quantitatively most important metabolite of 7-HC in human urine, occurring in 1000 times higher amounts than 7-hydroxycitronellol (7-HCO) or other potential metabolites. Therefore, an analytical method for 7-HCA was developed using stable isotope-labeled 7-HCA as internal standard (IS). The method includes a cleavage step of possible metabolite conjugates with an enzyme mix of ß-glucuronidase and arylsulfatase. Subsequent sample cleanup was performed by liquid-liquid extraction (LLE) with dichloromethane. The method was calibrated by calculating the linear regression between the analyte/IS ratio and the nominal 7-HCA concentrations in water. The method was validated according to approved standard guidelines and proved to be robust, reliable and sensitive for the human biomonitoring of 7-HC. The method was applied to urine samples of 40 adult volunteers from the general population. 7-HCA was quantifiable in urine of all subjects. Thus the developed method proved to be suitable for assessing the background exposure to 7-HC in the general population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess students' communication skills during clinical medical education and at graduation., Methods: We conducted an observational cohort study from 2007 to 2011 with 26 voluntary undergraduate medical students at Hamburg University based on video-taped consultations in year four and at graduation. 176 consultations were analyzed quantitatively with validated and non-validated context-independent communication observation instruments (interrater reliability ≥0.8). Based on observational protocols each consultation was also documented in free-text comments, salient topics were extracted afterwards., Results: 26 students, seven males, were enrolled in the survey. On average, graduates scored higher in differential-diagnostic questioning and time management but showed deficiencies in taking systematic and complete symptom-oriented histories, in communication techniques, in structuring consultations and in gathering the patients' perspectives. Patient-centeredness and empathy were rather low at graduation. Individual deficiencies could barely be eliminated., Conclusion: Medical students were able to enhance their clinical reasoning skills and their time management. Still, various communication deficiencies in final year students became evident regarding appropriate history taking, communication skills, empathy and patient-centeredness., Practice Implications: The necessity of developing a longitudinal communication curriculum with enhanced communication trainings and assessments became evident. A curriculum should ensure that students' communication competencies are firmly achieved at graduation., (Copyright © 2017. Published by Elsevier B.V.)

The application of computational fluid dynamics to coronary computed tomography angiography allows Fractional Flow Reserve (FFR) to be calculated non-invasively (FFR CT ), enabling computation of FFR from coronary computed tomography angiography acquired at rest both for individual lesions as well as along the entire course of a coronary artery. FFR CT , validated in a number of accuracy studies and a large clinical utility trial, is beginning to penetrate clinical practice. Importantly, while accuracy trials compared FFR CT to invasively measured FFR at a single point in the coronary tree, clinical reports of FFR CT provide information regarding a patient's entire coronary vasculature. Specifically, in distal coronary segments, calculated FFR CT values may be low and below 0.80 even in the absence of localized stenoses within the course of the artery. As a result, the reporting physician needs to understand how to interpret the findings in a clinically useful and thoughtful fashion. This review provides a brief overview of the background of both invasively measured and computationally derived FFR, explains changes in FFR along the course of normal coronary arteries and those affected by coronary atherosclerosis, and outlines the relevance of measurement location when interpreting and reporting FFR and FFR CT results., (Published by Elsevier Inc.)

The original CODIS database based on 13 core STR loci has been overwhelmingly successful for matching suspects with evidence. In order to increase the power of discrimination, reduce the possibility of adventitious matches, and expand global data sharing, the CODIS Core Loci Working Group determined the expansion of the CODIS core loci to 20 STR plus three additional "highly recommended" loci (SE33, DY391, Amelogenin) Hares, 2015, 2012 [1,2]. The QIAGEN Investigator 24plex QS and Investigator 24plex GO! Kits are 6-dye multiplex assays that contain all markers of the expanded 23 CODIS core loci along with a unique internal performance control that is co-amplified with the STR markers. The "Quality Sensor" generates additional information for quality control and performance checks. Investigator 24plex QS is designed for purified DNA from casework and reference samples, whereas 24plex GO! is dedicated to direct amplification of reference samples, like blood or buccal cells on FTA or swabs. A developmental validation study was performed on both assays. Here, we report the results of this study which followed the recommendations of the European Network of Forensic Science Institutes (ENFSI) [3] and the Revised Validation Guidelines of the Scientific Working Group on DNA Analysis Methods (SWGDAM) [4]. Data included are for PCR-based procedures e.g. reaction conditions, effects of PCR annealing temperature variations, amplification cycles or cyclers, sensitivity (also in the context of the Quality Sensor), performance with simulated inhibition, stability and efficiency, precision, reproducibility, mixture study, concordance, stutter, species specificity, and case-type samples. The validation results demonstrate that the Investigator 24plex QS and Investigator 24plex GO! Kits are robust and reliable identification assays as required for forensic DNA typing in forensic casework analysis and databasing., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

We developed and validated an efficient and robust method for the simultaneous quantification of 44 fatty acid species in human plasma via GC-TOF-MS. The method is characterized by its robustness, accuracy and precision covering a wide range of fatty acid species with various saturation degrees including short chain fatty acids (beginning with FA 4:0) and long chain fatty acids (up to FA 32:0). The fatty acids were methylated prior to analyses and subsequently detected as fatty acid methyl esters by means of GC-TOF-MS. A highly substituted polar column allowed the separation of geometrical and positional isomers of fatty acid species. The method was applied to plasma samples of a strictly diet controlled clinical smoking cessation study including 39 smokers followed over the course of three months after having quit. Statistical significant alterations within the fatty acid profile were observed when comparing the baseline (subjects still smoking) with one week, one month and three months of smoking cessation. After 3 months of smoking cessation, a partial recovery of alterations in the fatty acid profile evoked by smoking was observed. In conclusion, the developed fatty acid profiling method using GC-TOF-MS has proven as a reliable tool for the quantitative determination of 44 individual fatty acid species within clinical studies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The existence of perihemorrhagic ischemia in intracerebral hemorrhage (ICH) has been subject to intense debate. In contrast, the concept of reduced cerebral blood flow (CBF) in the perihemorrhagic zone (PHZ) is widely accepted. This report aims to demonstrate preliminary experience with endoscopic visualization of perihemorrhagic vessel compression in patients with ICH., Patients and Methods: Endoscopic findings in the PHZ during minimally invasive hematoma evacuation in six patients with basal ganglia ICH are described. 3D-Neuronavigation for exact real-time orientation and a translucent working channel for tissue visibility are used., Results: While entering the hematoma with the endoscope, the same distinct areas are illustrated in five patients: In the cortical entry zone, uncompressed vessels are present. In the subcortical white matter, vessel quantity shows its physiological rarification. In perihemorrhagic white matter adjacent to the ICH however, vessels appear to be almost completely absent. After hematoma-evacuation, the lack of vessels in the PHZ vanishes and in contrast, correlates of hyperperfusion are observed. Occurrence of these findings does not show correlation with clinical or radiological parameters. However, the only patient without vessel compression in the PHZ had the best neurological outcome in this small case series., Conclusion: We present visual correlates of mechanical vasoconstriction due to tissue compression in the PHZ of patients with basal ganglia ICH. Removal of the hematoma leads to visible reperfusion of the PHZ. These findings may help to understand the perihemorrhagic pathophysiology associated with focal reduction of cerebral blood flow and possibly ischemic changes in ICH., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The current study sought to demonstrate the advantages offered by fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in patients supported with continuous-flow left ventricular assist devices (CF-LVADs) in detecting infection and the consequent effect on clinical decisions., Methods: Between April 2009 and September 2013, 40 PET examinations were performed in 31 patients (78.1% men; mean age, 51.0 ± 14.9 years) supported with a CF-LVAD. In group A (19 examinations in 14 patients), PET/CT was performed to detect infectious focus in patients without external signs of driveline involvement but with at least two of the following infection signs: recurrent fever, positive blood culture, or elevated infectious indicators. In group B (21 examinations in 17 patients), PET/CT aimed to assess the internal extension of infection in patients with external signs of driveline infection., Results: In 50% of the cases of the patients in group A, abnormal (18)F-FDG uptake (9 patients) was related to VAD components. Matching the results with the final diagnosis, we reported 9 true-positive, 8 true-negative, no false-negative, and 2 false-positive findings. New information unrelated to VAD was found in 9 patients (50%): pneumonia in 3, colon diverticulitis in 3, sternal dehiscence in 1, paravertebral abscess in 1, and erysipelas in 1. In group B, superficial abnormal (18)F-FDG uptake was found at the piercing site of the driveline in 2 patients, deeper extension of infection along the driveline in 10, initial involvement of the pump housing in 2, and full involvement of the device in 4. These findings contributed to changing the clinical management in 84.2% of group A patients and in 85.7% of group B patients: 16 patients were scheduled for urgent transplantation, 2 underwent surgical revision of the driveline, 7 required prolonged antibiotic therapy, and 3 underwent colonoscopy., Conclusions: This single-center experience highlights the diagnostic value of PET/CT in detecting the localization and internal extension of infection to internal VAD components. Moreover, this information notably influences the therapeutic management., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To develop a framework to identify and classify interactions within and among treatments and conditions and to test this framework with guidelines on chronic heart failure (CHF) and its frequent comorbidity., Study Design and Setting: Text analysis of evidence-based clinical practice guidelines on CHF and 18 conditions co-occurring in ≥5% of CHF patients (2-4 guidelines per disease). We extracted data on interactions between CHF and comorbidity and key recommendations on diagnostic and therapeutic management. From a subset of data, we derived 13 subcategories within disease-disease (Di-Di-I), disease-drug (Di-D-I), drug-drug interactions (DDI) and synergistic treatments. We classified the interactions and tested the interrater reliability, refined the framework, and agreed on the matrix of interactions., Results: We included 48 guidelines; two-thirds provided information about comorbidity. In total, we identified N = 247 interactions (on average, 14 per comorbidity): 68 were Di-Di-I, 115 were Di-D-I, 12 were DDI, and 52 were synergisms. All 18 comorbidities contributed at least one interaction., Conclusion: The interaction matrix provides a structure to present different types of interactions between an index disease and comorbidity. Guideline developers may consider the matrix to support clinical decision making in multimorbidity. Further research is needed to show its relevance to improve guidelines and health outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To establish the diagnostic accuracy of the Total Score of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery (CERAD-NP) both for cross-sectional discrimination of Alzheimer disease (AD) dementia and short-term prediction of incident AD dementia., Design: Longitudinal cohort study with two assessments at a 1.5-year interval., Setting: Primary care sample randomly recruited via medical record registries., Participants: As part of the German Study on Ageing, Cognition, and Dementia (AgeCoDe), a sample of elderly individuals (N = 1,606; mean age: 84 years) was assessed., Measurements: Subjects were assessed with the CERAD-NP and followed up for 18 months (97.6% follow-up rate). Logistic regression and receiver-operating-characteristic (ROC) curve analysis were used to compare the diagnostic accuracy of the CERAD-NP Total Score (CTS) with that of single CERAD-NP scores and the Mini-Mental-State-Examination (MMSE) score., Results: ROC curve analysis resulted in excellent (area under the curve [AUC]: 0.97) cross-sectional discrimination between non-AD and AD dementia subjects. Prediction of incident AD dementia with the CTS was also very good (AUC: 0.89), and was significantly better than prediction based on the MMSE., Conclusions: The cross-sectional results confirm that the CTS is a highly accurate diagnostic tool for detecting AD dementia in elderly primary care patients. In addition, we provide evidence that the CTS is also accurate for the prediction of incident AD dementia. These findings further support the validity of the CTS as an index of overall cognitive functioning for detection and prediction of AD dementia., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Mass spectrometry is an ideal tool for investigations of the metabolome in human plasma. To investigate the impact of smoking on the human metabolome, we performed an untargeted metabolic fingerprinting using GC-TOF-MS with EDTA-plasma samples from 25 smokers and 25 non-smokers. The observed elevated levels in the monounsaturated fatty acids (MUFAs) in smokers were verified by a targeted analysis using GC-FID, which revealed also significantly alterations in saturated and polyunsaturated fatty acids in smokers (p<0.05, Mann-Whitney U test). Since the main fraction of fatty acids in plasma is esterified to phospholipids, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species composition in the plasma samples of the same subjects. The profiles of 39 PC and 40 PE species were analyzed with a newly developed and validated HILIC-ESI-MS/MS method. We were able to baseline separate the two lipid classes (PC from PE) by maintaining co-elution of individual lipid species of each class. The method shows a linear range from 0.5μM to 2000μM and an inter- and intraday coefficient of variation (CV)<20% across all analytes. Application of the validated method to the plasma samples of smokers and non-smokers, derived from a diet-controlled smoking study, revealed significantly elevated levels of PC and PE species containing MUFAs in smokers. In summary, we could demonstrate that there is a significantly altered total fatty acid profile, with increased MUFAs, in the plasma of smokers compared to non-smokers. Results obtained with the new HILIC-MS/MS method indicate that the altered fatty acid profile is also reflected in the PC and PE profile of smokers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Urinary determination of nicotine metabolites provides an ideal tool for the quantitative assessment of the tobacco use-related nicotine dose, provided that the considered metabolites comprise a large share of the amount taken up. A method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the sensitive, fast and robust analysis of nicotine and 10 major nicotine metabolites ("Nic+10"), including cotinine, trans-3'-hydroxy-cotinine, nicotine-N-glucuronide, cotinine-N-glucuronide, trans-3'-hydroxy-cotinine-O-glucuronide, nornicotine, norcotinine, nicotine-N'-oxide, cotinine-N'-oxide and 4-hydroxy-(3-pyridyl)-butanoic acid. Corresponding deuterated internal standards were spiked prior to a simple and straightforward solid phase extraction (SPE) procedure. Liquid chromatography was performed on a reversed phase C8 column and mass-specific detection was conducted in scheduled-MRM mode. The method was validated according to FDA Guidelines, showing excellent selectivity, precision, accuracy and robustness. The limits of quantification were in the range 0.2-2.3ng/ml for all analytes. The novel method was applied to human urine samples derived from 25 smoking subjects. Quantitative results were correlated against a previously used LC-MS/MS method and compared to reports from the literature. The relative molar profile of nicotine and its 10 major metabolites was in good agreement with the literature. In addition, correlation amongst the two methods was excellent for almost all analytes, whereas the accordance between both methods was moderate for hydroxy-cotinine-O-glucuronide and norcotinine. These deviations, however, could be explained. The current method allows the simultaneous determination of nicotine and its 10 major metabolites (metabolite coverage about 95% of the absorbed dose) from a small sample volume and within a reasonable amount of time. Due to its wide dynamic range, high sensitivity and high throughput capabilities, this method could serve as a powerful tool for quantifying the nicotine dose of smokers, passive smokers as well as novel tobacco and nicotine product users in clinical and epidemiological studies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To compare the costs of care for community-dwelling dementia patients with the costs of care for dementia patients living in nursing homes from the societal perspective., Design: Cross-sectional bottom-up cost of illness study nested within the multicenter German AgeCoDe-cohort., Setting: Community and nursing homes., Participants: One hundred twenty-eight community-dwelling dementia patients and 48 dementia patients living in nursing homes., Intervention: None., Measurements: Utilization and costs of medical care and long term care, including formal and informal social and nursing care based on proxy interviews. Informal care was valued using the replacement cost method., Results: Unadjusted mean annual total costs including informal care were €29,930 ($43,997) for community-dwelling patients and €33,482 ($49,218) for patients living in nursing homes. However, multiple regression analysis controlling for age, sex, deficits in basic and instrumental activities of daily living and comorbidity showed that living in the community significantly increased total costs by €11,344 ($16,676; P < .01) compared with living in a nursing home, mainly due to higher costs of informal care (+€20,585; +$30,260; P < .001)., Conclusion: From the societal perspective care for dementia patients living in the community tends to cost more than care in nursing homes when functional impairment is controlled for., (Copyright © 2014 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

The effect of sulfur mustard (SM) to the direct injured tissues of the skin, eyes and airways is well investigated. Little is known about the effect of SM to mesenchymal stem cells (MSC). However, this is an interesting aspect. Comparing the clinical picture of SM it is known today that MSC play an important role e.g. in chronic impaired wound healing. Therefore we wanted to get an understanding about how SM affects MSC and if these findings might become useful to get a better understanding of the effect of sulfur mustard gas with respect to skin wounds. We used mesenchymal stem cells, isolated from femoral heads from healthy donors and treated them with a wide range of SM to ascertain the dose-response-curve. With the determined inhibitory concentrations IC1 (1μM), IC5 (10μM), IC10 (20μM) and IC25 (40μM) we did further investigations. We analyzed the migratory ability and the differentiation capacity under influence of SM. Already very low concentrations of SM demonstrated a strong effect to the migratory activity whereas the differentiation capacity seemed not to be affected. Putting these findings together it seems to be likely that a link between MSC and the impaired wound healing after SM exposure might exist. Same as in patients with chronic impaired wound healing MSC had shown a reduced migratory activity. The fact that MSC are able to tolerate very high concentrations of SM and still do not lose their differentiation capacity may reveal new ways of treating wounds caused by sulfur mustard., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The integration of multiple morphogenic signalling pathways and transcription factor networks is essential to mediate neural crest (NC) cell induction, delamination, survival, stem-cell properties, fate choice and differentiation. Although the transcriptional control of NC development is well documented in mammals, the role of post-transcriptional modifications, and in particular ubiquitination, has not been explored. Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-) embryos identified profound deficiency of cranial NC cells in the absence of structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC cells and was found to positively regulate expression of the NC transcription factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a subset of cranial NC cells undergo apoptosis. In accordance with a lack of cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia, NC derived bone and malformation of the craniofacial skeleton. Our analyses therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC signalling pathways and transcription factor networks., (© 2013 Elsevier Inc. All rights reserved.)

Objective: To pilot-test feasibility, acceptance and learning-outcomes of a brief interdisciplinary communication skills training program in undergraduate medical education., Methods: A two-hour interdisciplinary communication skills program with simulated patients was developed and pilot-tested with clinical students at Hamburg University. Five psychosocial specialties facilitated the training. Composite effects were measured qualitatively and quantitatively., Results: Eighty students volunteered to participate in the pilot-program (intervention-group). Their evaluations of the program were very positive (1.1 on a six-point scale). Benefits were seen in feedback, increase of self-confidence, cross-disciplinary clinical and communication experience. Students who did not volunteer (n=206) served as the control-group. The intervention-group performed significantly better (p=0.023) in a primary care communication examination and female students performed better than males. Clinical teachers evaluated the pilot-training very positively with regard to learning-outcomes and feasibility. The positive results from the pilot-training led to implementation into the regular curriculum., Conclusions: A two-hour interdisciplinary communication skills training program is beneficial for medical students with regard to communication competencies, self-confidence and learning-outcomes., Practice Implication: The training is feasible within given time-frames and limited staff resources. The high teaching load for small-group-training are split between five specialties. The concept might be an interesting option for other faculties., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: HIV transmission risk among non-injection drug users is high due to the co-occurrence of drug use and sexual risk behaviors. The purpose of the current study was to identify patterns of drug use among polysubstance users within a high HIV prevalence population., Methods: The study sample included 409 substance users from the Pretoria region of South Africa. Substances used by 20% or more the sample included: cigarettes, alcohol, marijuana and heroin in combination, marijuana and cigarettes in combination, and crack cocaine. Latent class analysis was used to identify patterns of polysubstance use based on types of drugs used. Multivariate logistic regression analyses compared classes on demographics, sexual risk behavior, and disease status., Results: Four classes of substance use were found: MJ+Cig (40.8%), MJ+Her (30.8%), Crack (24.7%), and Low Use (3.7%). The MJ+Cig class was 6.7 times more likely to use alcohol and 3 times more likely to use drugs before/during sex with steady partners than the Crack class. The MJ+Cig class was 16 times more likely to use alcohol before/during sex with steady partners than the MJ+Her class. The Crack class was 6.1 times more likely to engage in transactional sex and less likely to use drugs before/during steady sex than the MJ+Her class., Conclusions: Findings illustrate patterns of drug use among a polysubstance using population that differ in sexual risk behavior. Intervention strategies should address substance use, particularly smoking as a route of administration (ROA), and sexual risk behaviors that best fit this high-risk population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: As the population ages, physicians encounter a growing number of patients who are treated with antiplatelet agents and present with severe conditions requiring urgent neurosurgical therapy. Standard laboratory investigations are insufficient to evaluate platelet activity and furthermore, it is difficult to evaluate effects of haemostatic measures on platelet function. In this article we report our initial experiences with the point-of-care device Multiplate® for assessment of platelet activity in neurosurgical emergencies on patients with a reported intake of antiplatelet medication., Methods: Multiplate® assessment of antiplatelet activity was carried out in 21 non-consecutive patients with a reported intake of antiplatelet medication (aspirin: n=21, clopidogrel: n=3, ticragrelor: n=1) and urgent admission to our hospital because of conditions such as intracranial haemorrhage requiring urgent neurosurgical therapy. Analysis was repeated in order to evaluate the effectiveness of haemostatic drugs and platelet concentrate transfusion on platelet activity in six patients., Results: No technical difficulties occurred and in all cases, results were obtained within 15 min. On admission, patients' arachidonic acid induced platelet activity was reduced by 44.4±33.5% (range: -79.7% to +44.3%) compared to the lower reference limit. Two patients had a normal platelet activity despite a reported intake of aspirin. Haemostatic measures significantly increased arachidonic acid induced platelet activity by 100±66% (p<0.005)., Conclusion: The Multiplate® device allowed rapid assessment of antiplatelet agent activity and evaluation of haemostatic measures on platelet activity. Further studies with larger patient numbers are needed, but this device may represent a valuable tool to improve treatment modalities in patients treated with antiplatelet medication and conditions requiring urgent neurosurgical therapy., (Copyright © 2013 Elsevier B.V. All rights reserved.)